A disproportionate analysis of novel oral anticoagulants in the overall and pediatric populations: a pharmacovigilance study based on FDA Adverse Event Reporting System database

A disproportionate analysis of novel oral anticoagulants in the overall and pediatric populations: a pharmacovigilance study based on FDA Adverse Event Reporting System database | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A disproportionate analysis of novel oral anticoagulants in the overall and pediatric populations: a pharmacovigilance study based on FDA Adverse Event Reporting System database Guimu Guo, Tingting Chen, Lingling Ye, Jintuo Zhou, Jinhua Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5713066/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective: This study utilizes the FDA Adverse Event Reporting System (FAERS) database to analyze and compare the actual adverse event (AE) signals of novel oral anticoagulants (NOACs) in the overall population and pediatric patients. Methods: This study conducted a comprehensive disproportionate analysis to assess the correlation between NOACs and AEs, covering from the third quarter of 2014 to the first quarter of 2024 in the overall and pediatric population. This analysis utilized statistical methodologies including the ROR, PRR, BCPNN, and EBGM to elucidate potential signals of drug-related AEs. Results: In the pediatric population, there were 820 AE reports related to NOACs. Injury, poisoning and procedural complications (20.98%), Vascular disorders (8.90%), and Respiratory, thoracic and mediastinal Disorders (3.41%) are significant SOC categories of AEs, and PTs show high signal strength such as Haemorrhoidal haemorrhage (n=3, ROR [95% CI]: 1008.19[240.54;4225.69], PRR [95% CI]: 1004.51[240.45;4196.45], IC [IC025]: 2.81[0.74], EBGM [EBGM05]: 628.19[1.54]), Pelvic venous thrombosis (n=3, ROR [95% CI]: 240.04[71.46;806.33], PRR [95% CI]: 239.17[71.48;800.28], IC [IC025]: 2.81[0.74], EBGM [EBGM05]:209.4[1.59]), and Thrombophlebitis (n=3, ROR [95% CI]: 129.25[39.86;419.09], PRR [95% CI]: 128.78[39.88;415.9], IC [IC025]: 2.8[0.74], EBGM [EBGM05]: 119.66[1.48]). Additionally, clinicians should be vigilant for unexpected and strongly signaled adverse events, like Low birth weight baby, Suicide attempt, Intentional self-injury, Foetal exposure during pregnancy, and Alopecia . Conclusion: This pharmacovigilance study provides valuable information on the use of NOACs in pediatric populations. It is crucial to closely monitor adverse events related to multiple systems and organs. However, the disproportionality analysis is hypothesis generating , causality and risk levels of adverse effects cannot be accurately inferred. novel oral anticoagulants pediatric disproportionate analysis adverse events FAERS database Figures Figure 1 Figure 2 1 Introduce Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, is a common thrombotic disorder in pediatrics, especially in hospitalized children [ 1 , 2 ] . In recent years, its incidence has continued to rise [ 3 ] . Anticoagulants conventionally used to treat VTE include vitamin K antagonists (VKAs), unfractionated heparin (UFH), and low molecular weight heparins (LMWHs) [ 4 ] . Although heparin and warfarin are cost-effective and highly efficacious, their use involves certain risks and limitations. For example, heparin may cause fatal heparin-induced thrombocytopenia and osteoporosis, while warfarin presents challenges such as a narrow therapeutic window, the need for frequent monitoring of anticoagulant activity, sensitivity to dietary and drug interactions, and complex dosage adjustments, limiting their clinical application [ 5 , 6 ] . Novel oral anticoagulants (NOACs), including direct factor Xa inhibitors—rivaroxaban, apixaban, and edoxaban—and the direct thrombin inhibitor, dabigatran, has revolutionized the management of VTE. These agents offer several advantages over traditional anticoagulants, like convenient oral administration, predictable pharmacokinetics, simplified treatment regimens, minimal interactions with food and drugs, immediate onset of therapeutic action, obviating the need for routine anticoagulant monitoring, and a reduced risk of hemorrhagic events [ 7 , 8 ] . Consequently, NOACs are increasingly favored over VKAs and are extensively utilized in adult populations for the prevention and treatment of conditions including stroke, deep vein thrombosis and pulmonary embolism. Given the scope of these developments, NOACs represent a promising alternative in the pediatric setting. Currently, NOACs have garnered approval for the management of pediatric VTE [ 9 ] . In December 2021, the US Food and Drug Administration (FDA) approved rivaroxaban and dabigatran for the treatment of pediatric patients, marking a significant advancement in therapeutic options [ 10 – 12 ] . The completion of the HOKUSAI-Jr Phase III study of edoxaban in children and the ongoing CANINES Phase IV trial of apixaban in children with venous thromboembolism [ 12 , 13 ] , imply a potential broadening of the anticoagulant spectrum for pediatric applications. Beyond the scope of VTE treatment, NOACs are under investigation for the prophylactic potential in pediatric populations with congenital and acquired heart diseases, as well as in oncological settings [ 12 ] . For pediatric patients, adverse drug reactions are generally mild to moderate. Contrasting with adults, pediatric patients more frequently report symptoms such as headache, fever, epistaxis, vomiting, and tachycardia, alongside elevated levels of total and conjugated bilirubin. The incidence of menorrhagia in adolescent women after menarche is similar to that in adults [ 14 ] . Thrombocytopenia, observed in adult postmarket experience, is similarly observed in pediatric clinical studies. Additionally, there have been some rare reports of adverse reactions, such as Cao Z et al., who reported erythema multiforme in a pediatric patient with antiphospholipid syndrome (APS) after rivaroxaban treatment [ 10 ] . Children exhibit significantly mature differences from adults in terms of hemostatic systems and pharmacokinetic parameters, presenting unique age-dependent characteristics. However, the use of NOACs in children largely relies on extrapolation from adult data, resulting in extremely limited experience in pediatric clinical practice [ 15 ] . There is a pressing need for more large-scale clinical trials to validate the safety and efficacy of these drugs in pediatric patients. Therefore, this study utilizes the FDA Adverse Event Reporting System (FAERS) database to analyze the actual adverse event (AE) signals of NOACs in the overall population and pediatric patients. Specifically, the discovery of related AE signals in the pediatric population is intended to raise awareness among clinicians regarding the use of NOACs in treating pediatric patients, reduce the occurrence of adverse reactions, and ensure the safety of NOACs. 2 Methods 2.1 Data sources and study design The FAERS database ( https://fs.fda.gov/extensions/FPDQDE-FAERS/FPD-QDE-FAERS.html ) includes over 15 million reports from more than 100 countries, with the majority originating from the United States, making it one of the largest pharmacovigilance databases in the world. The FAERS database contains information such as the demographics, clinical indications, treatment regimens, adverse events, treatment start date, and the event date. The reports in FAERS database are primarily submitted by consumers, healthcare professionals, and manufacturers. The FAERS database provides researchers with raw data for the analysis of drugs and adverse reactions. FAERS database is globally recognized as a critical reporting system and its official data can be downloaded for free from the Food and Drug Administration (FDA) website. This study obtained individual case reports on AEs related to NOACs from the FAERS database, covering from the third quarter of 2014 to the first quarter of 2024 in the overall population, and conducted a comprehensive disproportionate analysis. Based on the FAERS database, a total of 35,706,802 adverse event reports were collected, among which 1,374,645 reports were from the pediatric population. Out of all the reports, 554,605 were associated with NOACs. By excluding patients older than 18 years of age, as well as those records missing age or age_cod information, a final total of 820 adverse event reports related to NOACs in children were identified. 2.2 Pharmacovigilance Data Extraction and Analysis Using Navicat software (version 16; Hong Kong Z-Rays Digital Technology Limited; China) extracted the raw data from the FAERS database. Each quarterly ASCII data update in the FAERS database includes 7 sub-files, namely: DEMO, REAC, DRUG, OUTC, RPSR, THER, and INDI. The primaryid, a unique identifier for FAERS reports, facilitated the removal of duplicate records to ensure only the most updated versions were retained, with a specification that the report must denote the drug as the Primary Suspect (PS). Considering that duplicate or implausible reports can lead to serious errors, an extensive cleanup of the drug tables was initially performed each quarter, followed by a vertical merger of the 7 sub-files from each quarter into a master table. The DEMO and DRUG tables were deduplicated again to ensure a unique primaryid, thus guaranteeing that the final dataset did not contain duplicate reports. Finally, based on the unique primaryid, the INDI, REAC, RPSR, and THER tables were mapped to filter corresponding report events. The detailed processing steps of the FAERS database are illustrated in Fig. 1 . In this study, the names and commercial brands of the NOACs were identified through the FDA’s Orange Book and DrugBank as Rivaroxaban (Xarelto), Apixaban (Eliquis), Edoxaban (Lixiana, Savaysa), and Dabigatran (Pradaxa) [ 16 , 17 ] . The names of the adverse drug reactions (ADRs) were standardized using the Medical Dictionary for Regulatory Activities (MedDRA, version 26) [ 18 ] . According to MedDRA, the ADRs were coded as Preferred Terms (PTs) and corresponding System Organ Class (SOC) categories were listed to facilitate the comparison of potential signal strengths at the same level. 2.3 Descriptive analysis In the reports related to Rivaroxaban, Apixaban, Edoxaban, and Dabigatran, patient demographic characteristics (gender, age, and type of report) and clinical aspects (time onset and outcomes of the adverse events) were recorded. 2.4 Disproportionality analysis Currently, various national spontaneous reporting centers and the Uppsala Monitoring Centre employ a disproportionate analysis to identify potential signals between drugs and adverse events. This study evaluates the correlation between drugs and AEs using a 2 × 2 contingency table (see Supplemental Table S1 ) and employs multiple methods to detect signals, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM). The formulas for disproportionate analysis for signal detection as shown in Supplemental Table S2 . Signals of AE are identified using set thresholds: a ≥ 3, the lower bound of the 95% confidence interval of ROR greater than 1, PRR ≥ 2, IC025>0, EBGM05>2. Higher values of ROR, PRR, BCPNN, and EBGM indicate stronger AE signals, suggesting a stronger statistical relationship between the target drug and target AE. All data processing and analysis were calculated by excel software and plotted by origin (2021 version). 3 Results 3.1 Descriptive analysis From the third quarter of 2014 to the first quarter of 2024, the FAERS database detected AE reports related to Rivaroxaban, Apixaban, Edoxaban, and Dabigatran in the overall population as 228,621 (41.22%), 237,489 (42.82%), 12,589 (2.27%), and 76,806 (13.85%) respectively, and in the pediatric population as 476 (58.05%), 241 (29.39%), 5 (0.61%), and 98 (11.95%) respectively. Basic characteristics of the reported patients can be seen in Table 1 . Table 1 Characteristics of adverse events reports associated with novel oral anticoagulants. Categories NOACs used in the overall Population, N (%) NOACs used in the pediatric Population, N (%) Reported case 554605 820 Sex Female 264278 (47.65%) 413 (50.37%) Male 249588 (45.00%) 361 (44.02%) Unknown or missing 40715 (7.35%) 46 (5.61%) Report year 2014 24223 (4.37%) 41 (5.00%) 2015 58941 (10.63%) 43 (5.24%) 2016 64425 (11.62%) 87 (10.61%) 2017 65405 (11.79%) 71 (8.66%) 2018 62541 (11.28%) 94 (11.46%) 2019 63831 (11.51%) 62 (7.56%) 2020 73798 (13.31%) 123 (15.00%) 2021 50699 (9.14%) 65 (7.93%) 2022 46581 (8.40%) 130 (15.85%) 2023 35618 (6.42%) 70 (8.54%) 2024 8120 (1.46%) 34 (4.15%) Unknown or missing 423 (0.08%) Reporter country United States 358102 (64.57%) 386 (47.07%) Germany 33880 (6.11%) 71 (8.66%) Great Britain 17434 (3.14%) 29 (3.54%) France 16971 (3.06%) 64 (7.80%) Others 128218 (23.11%) 270 (32.92%) Reporter Consumer 304234 (54.86%) 223 (27.20%) Physician 142410 (25.68%) 297 (36.22%) Pharmacist 72600 (13.09%) 205(25.00%) Other health-professional 30674 (5.53%) 88 (10.73%) Lawyer 1624 (0.29%) 4 (0.49%) missing 3063 (0.55%) 3 (0.37%) Indication (top 5) Product used for unknown indication 179005(32.28%) 259(31.59%) Atrial fibrillation 118522(21.37%) 53(6.46%) Cerebrovascular accident prophylaxis 112732(20.33%) Deep vein thrombosis 39076(7.05%) 102(12.44%) Pulmonary embolism 23920(4.31%) Thrombosis prophylaxis 87(10.61%) Embolism venous 44(5.37%) Outcomes Death 42984 (14.4%) 18 (5.22%) Life-threatening 10617 (3.58%) 17 (4.93%) Hospitalization 102676 (34.61%) 135 (39.13%) Disability 4507 (1.52%) 7 (2.03%) Other serious illness 135202 (45.57%) 158 (45.80%) Congenital Anomaly 76 (0.02%) 8 (2.32%) Required Intervention to Prevent Permanent Impairment/Damage 633 (0.21%) 2 (0.58%) Adverse event occurrence time, days Median (Q1, Q3) 14(1.75,52.00) 71(11.50,307.50) Notably, female (overall population: 47.65%, pediatric patients: 50.37%) reported AEs more than males (overall population: 45%, pediatric patients: 44.02%). In the overall population, the highest reporting rate was from 2016–2020, while a declining trend in reports has been observed in recent years. For pediatric patients, the peak reporting year was 2022, accounting for 15.85% of reports. The majority of reports were submitted by medical professionals (overall population: 44.3%, pediatric patients: 71.95%) and predominantly from the United States (overall population: 64.57%, pediatric patients: 47.07%). In the overall population, NOACs were primarily used for Product used for unknown indication (32.28%), Atrial fibrillation (21.37%), and Cerebrovascular accident prophylaxis (20.33%). In the pediatric population, the main indication was for Product used for unknown indication (31.59%), Deep vein thrombosis (12.44%), and Thrombosis prophylaxis (12.44%). The median time to onset of AEs was 71 days in the overall population and 14 days in pediatric patients (Fig. 2 ), with the primary outcomes being other serious illnesses (overall population: 45.57%, pediatric patients: 45.80%) and hospitalization (overall population: 34.61%, pediatric patients: 39.13%). 3.2 Signals detection associated with NOACs in the overall population This study systematically analyzed the AE signals associated with NOACs across different SOCs in the overall population (Table 2 ) . The analysis encompassed 26 SOCs, with Gastrointestinal disorders (10.37%), Nervous system disorders (9.14%), and Vascular disorders (6.84%) emerging as the most frequently reported. Ranked by ROR, the SOC categories that exhibited the most significant AE signal strengths were Congenital, familial, and genetic disorders (n = 842, ROR [95% CI]: 40.71 [37.33;44.39], PRR [95% CI]: 40.65 [37.28;44.32], IC [IC025]: 4.63 [4.52], EBGM [EBGM05]: 25.16 [2.96]), Endocrine disorders (n = 188, ROR [95% CI]: 24.23 [20.48;28.66], PRR [95% CI]: 24.22 [20.47;28.65], IC [IC025]: 4.09 [3.85], EBGM [EBGM05]: 17.8 [2.43]), and Gastrointestinal disorders (n = 57477, ROR [95% CI]: 14.08 [13.95;14.22], PRR [95% CI]: 12.73 [12.62;12.84], IC [IC025]: 3.43 [3.41], EBGM [EBGM05]: 10.77 [2.35]). Table 2 Adverse event signals in various system organ classes for NOACs used in the overall and pediatric population. System organ class Case number Frequency (%) ROR (95% CI) PRR (95% CI) IC (IC025) EBGM (EBGM05) NOACs used in the overall population gastrointestinal disorders 57477 10.36% 14.08(13.95;14.22) 12.73(12.62;12.84) 3.43(3.41) 10.77(2.35) nervous system disorders 50670 9.14% 5.37(5.32;5.42) 4.97(4.93;5.01) 2.23(2.21) 4.68(1.53) vascular disorders 37956 6.84% 9.64(9.54;9.75) 9.05(8.96;9.15) 3.01(2.99) 8.04(2.06) injury, poisoning and procedural complications 36984 6.67% 3.21(3.17;3.24) 3.06(3.03;3.09) 1.57(1.55) 2.97(1.08) general disorders and administration site conditions 33965 6.12% 2.36(2.33;2.38) 2.27(2.25;2.3) 1.16(1.14) 2.23(0.79) cardiac disorders 27124 4.89% 3.66(3.62;3.71) 3.53(3.49;3.57) 1.76(1.74) 3.4(1.21) respiratory, thoracic and mediastinal disorders 21571 3.89% 4.58(4.51;4.64) 4.44(4.38;4.5) 2.07(2.05) 4.21(1.42) renal and urinary disorders 16774 3.02% 3.3(3.25;3.36) 3.23(3.18;3.28) 1.64(1.62) 3.13(1.12) blood and lymphatic system disorders 14072 2.54% 4.38(4.3;4.45) 4.29(4.22;4.36) 2.03(2) 4.08(1.38) investigations 10572 1.91% 4.46(4.37;4.55) 4.39(4.31;4.48) 2.06(2.03) 4.17(1.4) surgical and medical procedures 9876 1.78% 3.24(3.18;3.31) 3.2(3.14;3.27) 1.63(1.6) 3.1(1.11) reproductive system and breast disorders 4440 0.80% 5.28(5.12;5.45) 5.25(5.09;5.41) 2.3(2.25) 4.92(1.55) neoplasms benign, malignant and unspecified 4127 0.74% 2.62(2.54;2.7) 2.61(2.53;2.69) 1.35(1.29) 2.54(0.9) musculoskeletal and connective tissue disorders 3986 0.72% 2.35(2.28;2.43) 2.34(2.27;2.42) 1.2(1.15) 2.3(0.8) skin and subcutaneous tissue disorders 3482 0.63% 2.52(2.43;2.6) 2.51(2.42;2.59) 1.29(1.24) 2.45(0.87) eye disorders 3340 0.60% 2.3(2.22;2.38) 2.29(2.21;2.37) 1.17(1.11) 2.25(0.78) ear and labyrinth disorders 2132 0.38% 3.14(3.01;3.28) 3.13(3;3.27) 1.6(1.53) 3.03(1.06) infections and infestations 1930 0.35% 1.79(1.71;1.87) 1.78(1.7;1.87) 0.82(0.74) 1.76(0.54) metabolism and nutrition disorders 1562 0.28% 1.54(1.47;1.62) 1.54(1.47;1.62) 0.61(0.53) 1.53(0.4) product issues 1081 0.20% 2.91(2.74;3.09) 2.91(2.73;3.09) 1.5(1.4) 2.82(0.98) hepatobiliary disorders 1034 0.19% 1.7(1.6;1.81) 1.7(1.59;1.8) 0.75(0.64) 1.68(0.49) congenital, familial and genetic disorders 842 0.15% 40.71(37.33;44.39) 40.65(37.28;44.32) 4.63(4.52) 25.16(2.96) social circumstances 314 0.06% 1.5(1.34;1.67) 1.5(1.34;1.67) 0.57(0.38) 1.49(0.35) endocrine disorders 188 0.03% 24.23(20.48;28.66) 24.22(20.47;28.65) 4.09(3.85) 17.8(2.43) immune system disorders 164 0.03% 3.54(3.02;4.14) 3.54(3.02;4.14) 1.76(1.5) 3.4(1.05) pregnancy, puerperium and perinatal conditions 5 0.00% 6.6(2.63;16.58) 6.6(2.63;16.58) 2.06(0.49) 6.07(0.72) NOACs used in the pediatric population renal and urinary disorders 9 1.10% 21.91(11.31;42.44) 21.68(11.27;41.69) 4.2(3.06) 21.42(1.58) investigations 26 3.17% 12.28(8.3;18.17) 11.92(8.16;17.43) 5.5(4.85) 11.85(1.67) hepatobiliary disorders 3 0.37% 10.16(3.26;31.67) 10.13(3.26;31.44) 2.77(0.71) 10.07(0.74) vascular disorders 73 8.90% 8.93(7.02;11.36) 8.22(6.6;10.24) 6.45(6.06) 8.19(1.65) reproductive system and breast disorders 11 1.34% 7.58(4.18;13.77) 7.5(4.16;13.5) 4.37(3.34) 7.47(1.11) skin and subcutaneous tissue disorders 5 0.61% 6.07(2.51;14.64) 6.04(2.51;14.48) 3.37(1.81) 6.02(0.74) respiratory, thoracic and mediastinal disorders 28 3.41% 5.04(3.45;7.35) 4.9(3.4;7.06) 5.31(4.67) 4.89(1.09) pregnancy, puerperium and perinatal conditions 3 0.37% 4.28(1.37;13.3) 4.26(1.38;13.21) 2.73(0.66) 4.26(0.47) psychiatric disorders 12 1.46% 3.49(1.98;6.18) 3.46(1.97;6.07) 4.3(3.32) 3.45(0.7) musculoskeletal and connective tissue disorders 6 0.73% 3.45(1.55;7.72) 3.44(1.55;7.63) 3.52(2.1) 3.43(0.55) injury, poisoning and procedural complications 172 20.98% 2.87(2.42;3.39) 2.47(2.17;2.83) 5.76(5.51) 2.47(0.76) surgical and medical procedures 4 0.49% 2.78(1.04;7.43) 2.77(1.04;7.37) 3.02(1.25) 2.77(0.38) nervous system disorders 27 3.29% 2.51(1.71;3.68) 2.46(1.7;3.57) 4.9(4.25) 2.46(0.61) general disorders and administration site conditions 10 1.22% 2.17(1.16;4.06) 2.16(1.17;4) 3.95(2.88) 2.16(0.41) infections and infestations 3 0.37% 1.97(0.63;6.13) 1.97(0.64;6.09) 2.65(0.58) 1.97(0.22) gastrointestinal disorders 26 3.17% 1.63(1.1;2.41) 1.61(1.1;2.35) 4.56(3.91) 1.61(0.32) Abbreviations: BCPNN, bayesian confidence propagation neural network; CI, confidence interval; EBGM, empirical bayesian geometric mean; IC, information component; PRR, proportional reporting ratio; ROR, reporting odds ratio; NOACs, novel oral anticoagulants. The detailed analyses revealed the top 50 PTs for NOACs-associated AEs in the overall population, as summarized in Table 3 . Predominantly, the five most frequently PTs related to NOACs included Gastrointestinal hemorrhage (3.97%), Internal hemorrhage (0.67%), Lower gastrointestinal hemorrhage (0.45%), Hemorrhagic anemia (0.24%), and Embolic stroke (0.17%). Further analysis focused on the PTs exhibiting the strongest AE signal strengths sorted by ROR, including Procoagulant therapy (n = 740, ROR[95% CI]: 9393.13[3898.06;22634.54], PRR[95% CI]:9380.6[3892.89;22604.17], IC [IC025]:5.94[5.82], EBGM [EBGM05]:63.95[1.73]), Coagulation factor X level increased (n = 13, ROR[95% CI]༚823.99[107.79;6299.02], PRR[95% CI]:823.97[107.79;6298.85], IC [IC025]:4.23[3.3], EBGM [EBGM05]:59.78[0.54]), Spinal haematoma (n = 4, ROR[95% CI]༚253.53[28.34;2268.41], PRR[95% CI]:253.53[28.34;2268.39], IC [IC025]:2.96[1.2], EBGM [EBGM05]:51.51[0.44]), Thrombin time (n = 4, ROR[95% CI]༚253.53[28.34;2268.41], PRR[95% CI]:253.53[28.34;2268.39], IC [IC025]:2.96[1.2], EBGM [EBGM05]:51.51[0.44]), and Anti factor X antibody positive (n = 6, ROR[95% CI]༚190.15[38.39;942.13], PRR[95% CI]:190.15[38.38;942.12], IC [IC025]:3.38[1.97], EBGM [EBGM05]:48.29[0.78]). This study also unveiled unexpected AEs, including Cephalohematoma, Hematotympanum, Neoplasm malignant, Pituitary hemorrhage, and Pituitary apoplexy, alongside Antiphospholipid antibodies. Table 3 Adverse event signals in top 50 for NOACs used in the overall population. Preferred Terms Case number Frequency (%) ROR (95% CI) PRR (95% CI) IC (IC025) EBGM (EBGM05) Procoagulant therapy 740 0.13% 9393.13(3898.06;22634.54) 9380.6(3892.89;22604.17) 5.94(5.82) 63.95(1.73) Coagulation factor X level increased 13 0.00% 823.99(107.79;6299.02) 823.97(107.79;6298.85) 4.23(3.3) 59.78(0.54) Spinal haematoma 4 0.00% 253.53(28.34;2268.41) 253.53(28.34;2268.39) 2.96(1.2) 51.51(0.44) Thrombin time 4 0.00% 253.53(28.34;2268.41) 253.53(28.34;2268.39) 2.96(1.2) 51.51(0.44) Anti factor X antibody positive 6 0.00% 190.15(38.39;942.13) 190.15(38.38;942.12) 3.38(1.97) 48.29(0.78) Hepatic haemangioma rupture 5 0.00% 158.46(30.74;816.76) 158.46(30.74;816.75) 3.18(1.61) 45.99(0.74) Haemorrhagic arteriovenous malformation 596 0.11% 135.54(117.58;156.25) 135.4(117.46;156.08) 5.4(5.27) 43.85(3.28) Clotting factor transfusion 10 0.00% 126.77(43.33;370.88) 126.76(43.33;370.88) 3.84(2.76) 42.92(1.28) Thrombin time abnormal 15 0.00% 118.85(50.39;280.31) 118.84(50.39;280.3) 4.18(3.31) 41.99(1.58) Thrombin time prolonged 69 0.01% 106.68(72.48;157.01) 106.67(72.48;156.99) 4.98(4.58) 40.39(2.51) Cerebral ventricular rupture 100 0.02% 99.05(72.38;135.56) 99.04(72.37;135.53) 5.04(4.71) 39.26(2.68) Atrial thrombosis 814 0.15% 96.58(86.59;107.71) 96.44(86.47;107.55) 5.25(5.13) 38.85(3.28) CHA2DS2-VASc annual stroke risk high 6 0.00% 95.07(26.83;336.92) 95.07(26.83;336.91) 3.31(1.9) 38.63(1.03) Factor Xa activity abnormal 3 0.00% 95.07(15.89;569) 95.07(15.89;569) 2.6(0.53) 38.63(0.61) Gastrointestinal angiodysplasia haemorrhagic 80 0.01% 87.44(62.36;122.6) 87.42(62.35;122.58) 4.93(4.56) 37.32(2.58) Anti factor X activity increased 22 0.00% 82.03(43.56;154.47) 82.02(43.56;154.46) 4.35(3.62) 36.32(1.91) Diverticulum intestinal haemorrhagic 885 0.16% 72.87(66.16;80.26) 72.75(66.06;80.13) 5.08(4.97) 34.41(3.21) Basal ganglia haemorrhage 289 0.05% 64.99(55.15;76.58) 64.96(55.13;76.53) 4.95(4.76) 32.59(2.96) Duodenal vascular ectasia 7 0.00% 63.38(22.23;180.71) 63.38(22.23;180.7) 3.39(2.08) 32.19(1.22) Contraindication to surgery 5 0.00% 63.38(18.35;218.94) 63.38(18.35;218.94) 3.07(1.51) 32.19(1.01) Peripheral artery aneurysm rupture 4 0.00% 63.38(15.85;253.44) 63.38(15.85;253.44) 2.85(1.08) 32.19(0.87) Lower gastrointestinal haemorrhage 2513 0.45% 61.58(58.29;65.06) 61.31(58.04;64.76) 4.98(4.91) 31.66(3.27) Haemorrhagic anaemia 1305 0.24% 60.6(56.17;65.38) 60.46(56.05;65.22) 4.96(4.87) 31.43(3.2) Anastomotic ulcer haemorrhage 51 0.01% 59.87(40.83;87.78) 59.86(40.83;87.77) 4.6(4.13) 31.27(2.35) Thalamus haemorrhage 285 0.05% 59.65(50.74;70.12) 59.62(50.72;70.08) 4.89(4.69) 31.21(2.93) Traumatic intracranial haematoma 8 0.00% 56.34(21.74;146.03) 56.34(21.74;146.03) 3.48(2.26) 30.3(1.32) High frequency ablation 130 0.02% 53.52(42.37;67.59) 53.5(42.37;67.57) 4.73(4.44) 29.47(2.68) Atrio-oesophageal fistula 5 0.00% 52.82(16.12;173.07) 52.82(16.12;173.07) 3.04(1.47) 29.26(1.03) Chronic gastrointestinal bleeding 89 0.02% 51.29(38.79;67.83) 51.28(38.78;67.81) 4.64(4.29) 28.79(2.54) Pericardial haemorrhage 600 0.11% 51.17(45.95;56.98) 51.11(45.9;56.92) 4.81(4.68) 28.74(3.02) Failure to suspend medication 71 0.01% 50.01(36.64;68.26) 50(36.63;68.25) 4.57(4.18) 28.39(2.45) Gastrointestinal endoscopic therapy 20 0.00% 48.76(27.22;87.34) 48.76(27.22;87.34) 4.08(3.33) 27.99(1.86) Embolic stroke 930 0.17% 48.51(44.54;52.84) 48.44(44.47;52.75) 4.78(4.67) 27.89(3.06) Gastrointestinal haemorrhage 22006 3.97% 48.5(47.66;49.37) 46.62(45.82;47.43) 4.77(4.75) 27.29(3.25) Embolic cerebral infarction 182 0.03% 48.08(39.65;58.3) 48.06(39.64;58.28) 4.69(4.45) 27.77(2.74) Haemorrhagic hepatic cyst 31 0.01% 47.93(30.06;76.41) 47.92(30.06;76.41) 4.28(3.68) 27.72(2.08) Gastrointestinal vascular malformation haemorrhagic 138 0.02% 47.81(38.33;59.63) 47.8(38.32;59.62) 4.66(4.38) 27.68(2.66) Prostatic varices 3 0.00% 47.54(10.64;212.4) 47.54(10.64;212.4) 2.52(0.45) 27.59(0.74) Post procedural haematuria 52 0.01% 46.43(32.46;66.39) 46.42(32.46;66.39) 4.44(3.98) 27.22(2.31) Ventricular drainage 16 0.00% 46.1(24.21;87.77) 46.1(24.21;87.77) 3.92(3.08) 27.11(1.73) Cerebral ventricle collapse 29 0.01% 45.95(28.49;74.12) 45.95(28.49;74.12) 4.23(3.61) 27.06(2.04) Adrenal haemorrhage 134 0.02% 45.92(36.77;57.36) 45.91(36.76;57.34) 4.62(4.34) 27.04(2.64) Subgaleal haematoma 54 0.01% 45.04(31.78;63.84) 45.03(31.77;63.83) 4.44(3.98) 26.74(2.32) Anticoagulation drug level increased 106 0.02% 43.63(34.07;55.88) 43.63(34.07;55.87) 4.55(4.23) 26.25(2.55) Haematuria traumatic 21 0.00% 42.94(24.68;74.72) 42.94(24.67;74.71) 4.04(3.31) 26(1.87) Haemorrhagic erosive gastritis 93 0.02% 42.41(32.62;55.15) 42.41(32.61;55.14) 4.51(4.17) 25.81(2.5) Activated partial thromboplastin time 6 0.00% 42.26(15.04;118.72) 42.25(15.04;118.72) 3.15(1.73) 25.75(1.16) Russell's viper venom time abnormal 4 0.00% 42.26(11.92;149.74) 42.25(11.92;149.74) 2.78(1.01) 25.75(0.92) Internal haemorrhage 3725 0.67% 41.02(39.36;42.75) 40.75(39.11;42.46) 4.65(4.6) 25.19(3.1) Mesenteric haemorrhage 23 0.00% 40.5(24;68.33) 40.49(24;68.33) 4.05(3.35) 25.1(1.91) Abbreviations: BCPNN, bayesian confidence propagation neural network; CI, confidence interval; EBGM, empirical bayesian geometric mean; IC, information component; PRR, proportional reporting ratio; ROR, reporting odds ratio; NOACs, novel oral anticoagulants. 3.3 Signals detection associated with NOACs in Pediatric Population In the pediatric, the AE signals associated with NOACs were fewer when compared to the overall population, and identified 16 SOCs of AE signals, as delineated in Table 2 . The SOC categories with the highest frequencies included Injury, poisoning and procedural complications (20.98%), Vascular disorders (8.90%), and Respiratory, thoracic and mediastinal Disorders (3.41%). Ranked by ROR, particularly prominent AE signal strengths were found in the SOCs of Renal and urinary disorders (n = 9, ROR [95% CI]: 21.91[11.31;42.44], PRR [95% CI]: 21.68[11.27;41.69], IC [IC025]: 4.2[3.06], EBGM [EBGM05]: 21.42[1.58]), Investigations (n = 26, ROR [95% CI]: 12.28[8.3;18.17], PRR [95% CI]: 11.92[8.16;17.43], IC [IC025]: 5.5[4.85], EBGM [EBGM05]: 11.85[1.67]), and Hepatobiliary disorders (n = 3, ROR [95% CI]: 10.16[3.26;31.67], PRR [95% CI]: 10.13[3.26;31.44], IC [IC025]: 2.77[0.71], EBGM [EBGM05]: 10.07[0.74]). This study identified the top 50 PTs signals associated with NOACs in the pediatric population, as shown in Table 4 . The five most frequently PTs related to NOACs were Accidental exposure to product by child (3.54%), Deep vein thrombosis (2.93%), Product use issue (2.07%), Intentional overdose (1.71%), and Thrombosis (1.59%). The PTs exhibiting highest signal strength in the pediatric population sorted by ROR, including Haemorrhoidal haemorrhage (n = 3, ROR [95% CI]: 1008.19[240.54;4225.69], PRR [95% CI]: 1004.51[240.45;4196.45], IC [IC025]: 2.81[0.74], EBGM [EBGM05]: 628.19[1.54]), Pelvic venous thrombosis (n = 3, ROR [95% CI]: 240.04[71.46;806.33], PRR [95% CI]: 239.17[71.48;800.28], IC [IC025]: 2.81[0.74], EBGM [EBGM05]:209.4[1.59]), Thrombophlebitis (n = 3, ROR [95% CI]: 129.25[39.86;419.09], PRR [95% CI]: 128.78[39.88;415.9], IC [IC025]: 2.8[0.74], EBGM [EBGM05]: 119.66[1.48]), Deep vein thrombosis (n = 24, ROR [95% CI]: 126.94[83.38;193.26], PRR [95% CI]: 123.25[81.89;185.51], IC [IC025]: 5.59[4.91], EBGM [EBGM05]: 114.87[3.12]), and Activated partial thromboplastin time prolonged (n = 6, ROR [95% CI]: 70.76[31.17;160.6], PRR [95% CI]: 70.25[31.13;158.52], IC [IC025]: 3.69[2.28], EBGM [EBGM05]: 67.46[1.86]). This study had also found unexpected AE signals in pediatric patients such as Low birth weight baby, Suicide attempt, Intentional self-injury, Foetal exposure during pregnancy, and Alopecia. Table 4 Adverse event signals in top 50 for NOACs used in the pediatric population. Preferred Terms Case number Frequency (%) ROR (95% CI) PRR (95% CI) IC (IC025) EBGM (EBGM05) Haemorrhoidal haemorrhage 3 0.37% 1008.19(240.54;4225.69) 1004.51(240.45;4196.45) 2.81(0.74) 628.19(1.54) Pelvic venous thrombosis 3 0.37% 240.04(71.46;806.33) 239.17(71.48;800.28) 2.81(0.74) 209.4(1.59) Thrombophlebitis 3 0.37% 129.25(39.86;419.09) 128.78(39.88;415.9) 2.8(0.74) 119.66(1.48) Deep vein thrombosis 24 2.93% 126.94(83.38;193.26) 123.25(81.89;185.51) 5.59(4.91) 114.87(3.12) Activated partial thromboplastin time prolonged 6 0.73% 70.76(31.17;160.6) 70.25(31.13;158.52) 3.69(2.28) 67.46(1.86) Prothrombin time prolonged 6 0.73% 68.83(30.34;156.16) 68.33(30.29;154.14) 3.69(2.28) 65.69(1.84) Ischaemic stroke 3 0.37% 48.47(15.35;153.05) 48.29(15.36;151.88) 2.8(0.73) 46.97(1.22) Thrombosis 13 1.59% 48.27(27.69;84.13) 47.52(27.5;82.12) 4.72(3.79) 46.24(2.2) Pulmonary embolism 11 1.34% 46.42(25.4;84.83) 45.81(25.27;83.06) 4.5(3.47) 44.62(2.08) Skin laceration 3 0.37% 35.5(11.29;111.61) 35.37(11.3;110.75) 2.8(0.73) 34.66(1.13) International normalised ratio increased 5 0.61% 33.55(13.81;81.52) 33.35(13.8;80.61) 3.44(1.88) 32.72(1.44) Haematuria 9 1.10% 21.91(11.31;42.44) 21.68(11.27;41.69) 4.2(3.06) 21.42(1.58) Menorrhagia 8 0.98% 18.96(9.41;38.19) 18.78(9.39;37.58) 4.04(2.83) 18.59(1.45) Accidental exposure to product by child 29 3.54% 16.88(11.63;24.49) 16.31(11.39;23.37) 5.7(5.08) 16.17(1.92) Cerebrovascular accident 4 0.49% 16.33(6.08;43.82) 16.25(6.09;43.41) 3.14(1.38) 16.11(1.04) Gastrointestinal haemorrhage 6 0.73% 13.78(6.15;30.86) 13.69(6.15;30.47) 3.65(2.24) 13.58(1.16) Haematoma 3 0.37% 12.44(3.99;38.82) 12.4(3.99;38.53) 2.78(0.71) 12.32(0.8) Haemoptysis 3 0.37% 11.53(3.7;35.97) 11.49(3.7;35.7) 2.78(0.71) 11.42(0.78) Cholestasis 3 0.37% 10.16(3.26;31.67) 10.13(3.26;31.44) 2.77(0.71) 10.07(0.74) Liver function test increased 3 0.37% 9.84(3.16;30.68) 9.81(3.16;30.45) 2.77(0.7) 9.76(0.73) Product prescribing issue 3 0.37% 8.9(2.86;27.74) 8.87(2.86;27.54) 2.77(0.7) 8.83(0.7) Epistaxis 9 1.10% 7.19(3.72;13.88) 7.12(3.71;13.65) 4.11(2.97) 7.09(1.01) Accidental exposure to product 8 0.98% 6.32(3.15;12.7) 6.27(3.14;12.51) 3.95(2.74) 6.25(0.91) Alopecia 5 0.61% 6.07(2.51;14.64) 6.04(2.51;14.48) 3.37(1.81) 6.02(0.74) Leukopenia 4 0.49% 5.72(2.14;15.3) 5.69(2.14;15.16) 3.09(1.33) 5.68(0.65) Intentional product use issue 6 0.73% 5.47(2.45;12.24) 5.44(2.45;12.09) 3.58(2.17) 5.43(0.76) Haemorrhage 8 0.98% 5.1(2.54;10.24) 5.06(2.54;10.09) 3.92(2.71) 5.05(0.81) Intentional overdose 14 1.71% 4.54(2.67;7.7) 4.48(2.66;7.53) 4.55(3.64) 4.47(0.88) Anaemia 7 0.85% 4.36(2.07;9.18) 4.33(2.07;9.06) 3.74(2.44) 4.32(0.69) Peripheral swelling 3 0.37% 4.31(1.39;13.42) 4.3(1.39;13.32) 2.73(0.66) 4.29(0.47) Low birth weight baby 3 0.37% 4.28(1.37;13.3) 4.26(1.38;13.21) 2.73(0.66) 4.26(0.47) Suicide attempt 9 1.10% 4.13(2.14;7.97) 4.1(2.14;7.85) 4.02(2.88) 4.09(0.73) Product administered to patient of inappropriate age 4 0.49% 4.07(1.52;10.89) 4.06(1.52;10.79) 3.06(1.3) 4.05(0.52) Hepatic enzyme increased 3 0.37% 3.92(1.26;12.19) 3.91(1.26;12.11) 2.72(0.66) 3.9(0.44) Drug administered to patient of inappropriate age 7 0.85% 3.88(1.84;8.18) 3.86(1.84;8.08) 3.72(2.42) 3.85(0.64) Haemoglobin decreased 3 0.37% 3.84(1.23;11.93) 3.83(1.23;11.85) 2.72(0.65) 3.82(0.43) Pain in extremity 6 0.73% 3.45(1.55;7.72) 3.44(1.55;7.63) 3.52(2.1) 3.43(0.55) Product dose omission 3 0.37% 3.25(1.05;10.11) 3.24(1.05;10.04) 2.71(0.64) 3.24(0.38) Fall 4 0.49% 3.24(1.21;8.67) 3.23(1.22;8.6) 3.04(1.27) 3.23(0.44) Treatment noncompliance 3 0.37% 3.06(0.98;9.52) 3.05(0.99;9.46) 2.7(0.63) 3.05(0.36) Paraesthesia 3 0.37% 3.04(0.98;9.44) 3.03(0.98;9.38) 2.7(0.63) 3.03(0.36) Vaginal haemorrhage 3 0.37% 2.89(0.93;8.98) 2.88(0.93;8.92) 2.7(0.63) 2.88(0.34) Hospitalisation 4 0.49% 2.78(1.04;7.43) 2.77(1.04;7.37) 3.02(1.25) 2.77(0.38) Thrombocytopenia 4 0.49% 2.41(0.9;6.44) 2.4(0.9;6.39) 3(1.23) 2.4(0.33) Intentional self-injury 3 0.37% 2.36(0.76;7.35) 2.36(0.76;7.3) 2.67(0.6) 2.36(0.28) Intentional product misuse 3 0.37% 2.29(0.74;7.11) 2.28(0.74;7.07) 2.67(0.6) 2.28(0.27) Wrong technique in product usage process 5 0.61% 2.26(0.94;5.44) 2.25(0.94;5.39) 3.23(1.67) 2.25(0.34) Accidental overdose 3 0.37% 2.13(0.69;6.64) 2.13(0.69;6.6) 2.66(0.59) 2.13(0.24) Product use issue 17 2.07% 2(1.24;3.24) 1.98(1.24;3.17) 4.4(3.58) 1.98(0.42) COVID-19 3 0.37% 1.97(0.63;6.13) 1.97(0.64;6.09) 2.65(0.58) 1.97(0.22) Abbreviations: BCPNN, bayesian confidence propagation neural network; CI, confidence interval; EBGM, empirical bayesian geometric mean; IC, information component; PRR, proportional reporting ratio; ROR, reporting odds ratio; NOACs, novel oral anticoagulants Overall, a comparative analysis between the pediatric and overall populations reveals distinct differences in the signal strength of AE associated with NOACs. At the SOC level, the pediatric population displays significantly signal strengths in the SOCs pertaining to Reproductive system and breast disorders, Renal and urinary disorders, Skin and subcutaneous tissue disorders, Respiratory, thoracic and mediastinal disorders, Musculoskeletal and connective tissue disorders, Investigations, Infections and infestations, and Hepatobiliary disorders, while the overall population exhibits more pronounced signal strengths in Gastrointestinal disorders, Nervous system disorders, Pregnancy, puerperium and perinatal conditions, General disorders and administration site conditions, Vascular disorders, and Injury, poisoning and procedural complications. Besides, a psychiatric AE signal is mined in the pediatric population, which is not present in the overall population (Table 2 ). 4 Discussion Recently, there has been a trend towards using NOACs for the treatment of VTE in pediatric patients. Yet now, the robustness of data concerning the efficacy and safety of NOACs in pediatric patients remains scant, largely extrapolated from adult clinical trials or derived from observational cohorts. This study undertakes a comprehensive analysis using the FAERS database to systematically compare and evaluate the AE signals associated with NOACs in both the overall and pediatric populations. In the investigation of NOACs within the pediatric population, the Diversity trial evaluated the efficacy and safety of traditional anticoagulants versus dabigatran for treating VTE in children under 18 years. This trial reported that 77% of pediatric participants treated with dabigatran experienced adverse events, with no significant variation observed across different age groups. Predominant adverse events included gastrointestinal symptoms (25%), headache (10%), and fever (6%) [ 19 ] . Another investigation conducted by Male C et al. assessed the effectiveness and safety of rivaroxaban in pediatric VTE treatment. 70% of pediatric patients reported adverse events subsequent to rivaroxaban administration, with the most frequent including infections (33%), gastrointestinal diseases (31%), respiratory diseases (24%), neurological diseases (24%), injuries, poisonings, and procedural complications (22%), skin and subcutaneous tissue disorders (19%), and musculoskeletal and connective tissue disorders (16%) [ 20 ] . Furthermore, the present investigation has elucidated significantly elevated pharmacovigilance signals for Reproductive system and breast disorders, Renal and urinary disorders, Investigations, and Hepatobiliary disorders in the pediatric population compared to the overall population. Pertinent to disorders of the reproductive system and breast in pediatric subjects, prominent pharmacovigilance signals were discerned for menorrhagia and vaginal haemorrhage. Notably, the signal intensity for menorrhagia was markedly elevated in the pediatric cohort (n = 8, ROR [95% CI]: 18.96[9.41;38.19], PRR [95% CI]: 18.78[9.39;37.58], IC [IC025]: 4.04[2.83], EBGM [EBGM05]: 18.59[1.45]) in comparison to the overall population (n = 1146, ROR [95% CI]: 7.97[7.49;32.67], PRR [95% CI]: 11.13[4.26;32.44], IC [IC025]: 3.77[1.71], EBGM [EBGM05]: 11.07[1.74]), while the signal strength for vaginal haemorrhage demonstrated a lower magnitude in the pediatric cohort (n = 3, ROR [95% CI]:2.89[0.93;8.98], PRR [95% CI]: 2.88[0.93;8.92], IC [IC025]: 2.7[0.63], EBGM [EBGM05]: 2.88[0.34]) as compared to the overall population (n = 1555, ROR [95% CI]: 4.42[4.2;33.67], PRR [95% CI]: 12.13[5.26;33.44], IC [IC025]: 4.77[2.71], EBGM [EBGM05]: 12.07[2.74]). Recent studies documented a low incidence of major bleeding (MB) or clinically relevant non-major bleeding (CRNMB); however, the occurrence of other types of abnormal uterine bleeding (AUB) ranged from 15.8–50%. In pediatric trials, 19% of female patients experienced menorrhagia while undergoing treatment with rivaroxaban [ 21 ] . When broadening the diagnostic criteria to encapsulate conditions, the incidence of AUB significantly escalates. This phenomenon might account for the heightened reported prevalence of AUB in pediatric studies compared to those conducted in adult populations. Additionally, the elevated prevalence of AUB attributed to anovulatory cycles in adolescents may also contribute to this disparity [ 20 – 22 ] . At the PT level, findings such as accidental exposure to the product by a child, drug administered to a patient of inappropriate age, product use issues, and off-label use underscore the necessity for meticulous and reasonable application of NOACs in pediatric. Surprisingly, signals for psychiatric disorders, including suicide attempts and intentional self-injury, were detected in pediatric patients, a phenomenon not observed in the overall population, suggesting that healthcare professionals should remain vigilant regarding the potential psychiatric risks associated with NOACs use in children. In adult patients, the prevalent adverse reaction with NOACs is bleeding, especially with rivaroxaban, apixaban is associated with elevated incidence and risk of cardiovascular and cerebral events, whereas edoxaban shows more prominent risk in terms of renal and urinary systems [ 23 – 27 ] . In this study, bleeding signals were frequently present in the overall population, particularly in the gastrointestinal, nervous, and vascular and lymphatic systems (Table 2 ). The AEs signals related to Congenital, familial, and genetic disorders were the strongest in SOC level, and the PTs exhibiting significant signal strength in this SOC level were Haemorrhagic arteriovenous malformation (n = 596, ROR[95% CI]: 135.54[117.58;156.25], PRR[95% CI]: 135.40[117.46;156.08], IC [IC025]: 5.40[5.27], EBGM [EBGM05]: 43.85[3.28]) and Gastrointestinal arteriovenous malformation (n = 63, ROR[95% CI]: 36.64[26.87;49.96], PRR[95% CI]: 36.63[26.86;49.96], IC [IC025]: 4.32[3.91], EBGM [EBGM05]: 23.58[2.32]). Wu J et al., based on the FAERS database, also identified a high signal strength at the PT level for Haemorrhagic arteriovenous malformations [ 28 ] . This investigation additionally revealed signals of AEs associated with NOACs in overall population, including Cephalhaematoma, Haematotympanum, Malignant Neoplasm, Pituitary apoplexy, and Antiphospholipid antibodies. Despite these AEs not being explicitly mentioned in the package insert, but their occurrence has been documented in clinical case reports. For instance, Ly S et al. described a patient with pituitary adenoma suffered pituitary hemorrhage during treatment with Rivaroxaban [ 29 ] . This emphasizes the necessity for heightened clinical vigilance and monitoring of such adverse reactions when administering NOACs. When investigating the disparities in anticoagulant utilization between pediatric and adult populations, multiple critical factors warrant consideration. On the one hand, the hemostatic system in children evolves with age [ 30 ] . There are significant differences in the plasma concentrations of hemostatic proteins that regulate thrombus formation and dissolution across different age groups, ranging from preterm infants to adults. For example, full-term neonates exhibit antithrombin levels that are only 50–75% of those found in adults, with even lower levels observed in preterm infants. These concentrations generally approximate adult levels by the age of 6–12 months [ 31 , 32 ] . On the other hand, the pharmacokinetics (PK) and pharmacodynamics (PD) of anticoagulants are also age-dependent. Children have lower plasma proteins, increased apparent volume of distribution, increased clearance rates, and shorter half-lives, leading to PK and PD differences between children and adults, as well as dietary types can significantly influence drug absorption, particularly in neonates [ 11 ] . Moreover, the difficulty of administration and the epidemiology of VTE also contribute to the differences in anticoagulant use between children and adults. There are several limitations to using the FAERS database for pharmacovigilance analysis. Primarily, while the frequency of reports can be estimated, the actual incidence of AE associated with NOACs cannot be determined through this spontaneous reporting system. Additionally, the sources of the reports in the FAERS database are heterogeneous. These reports frequently lack comprehensive clinical details constrains our capacity to thoroughly examine the AE signals related to NOACs. Nevertheless, the FAERS database continues to serve as one of the largest repositories of post-marketing drug event data globally, amassing millions of reports from both the United States and internationally. This extensive and varied dataset offers a crucial resource for investigating potential drug-AE associations, thereby playing a pivotal role in drug safety. 5 Conclusion NOACs are widely used in the treatment of various thrombotic diseases, and associated with a spectrum of potential adverse reactions. This pharmacovigilance study provides valuable information on the use of NOACs in pediatric populations. It is crucial to closely monitor adverse events related to the Reproductive system and breast disorders, Renal and urinary disorders, Skin and subcutaneous tissue disorders, Investigations, Vascular disorders and Hepatobiliary disorders. Additionally, clinicians should be vigilant for unexpected and strongly signaled adverse events, such as Low birth weight baby, Suicide attempt, Intentional self-injury, Foetal exposure during pregnancy, and Alopecia found in pediatric population. Declarations Clinical trial number Not applicable Ethical considerations Not applicable Consent to participate Not applicable Consent for publication Not applicable Data availability These data can be found at: https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html. Further inquiries can be directed to the corresponding author. Author contributions GG: Data curation, Formal Analysis, Investigation, Writing–original draft, Writing–review and editing. TC: Formal Analysis, Visualization, Writing–original draft, Writing–review and editing. LY: Formal Analysis, Visualization, Writing–review and editing. JZ: Formal Analysis, Writing–review and editing. JZ: Conceptualization, Methodology, Writing–review and editing. Funding This work was supported by the Natural Science Foundation of Fujian Province (No.2022J011037) Acknowledgment The authors would like to thank the FAERS database for freely providing the open-source data. They also thank the experts who provided valuable suggestions for the successful completion of this study. Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher ’ s note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. References Raffini L, Huang YS, Witmer C, Feudtner C. Dramatic increase in venous thromboembolism in children's hospitals in the United States from 2001 to 2007. Pediatrics 2009; 124(4):1001-1008. doi: 10.1542/peds.2009-0768 Stein PD, Kayali F, Olson RE. Incidence of venous thromboembolism in infants and children: data from the National Hospital Discharge Survey. J Pediatr 2004; 145(4):563-565. doi: 10.1016/j.jpeds.2004.06.021 Yee DL, O’Brien SH, Young G. Pharmacokinetics and Pharmacodynamics of Anticoagulants in Paediatric Patients. Clinical Pharmacokinetics 2013; 52(11):967-980. doi: 10.1007/s40262-013-0094-1 Badimon JJ, Escolar G, Zafar MU. Factor XI/XIa Inhibition: The Arsenal in Development for a New Therapeutic Target in Cardio- and Cerebrovascular Disease. J Cardiovasc Dev Dis 2022; 9(12). doi: 10.3390/jcdd9120437 Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141(2 Suppl):e44S-e88S. doi: 10.1378/chest.11-2292 Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141(2 Suppl):e24S-e43S. doi: 10.1378/chest.11-2291 Mikler J, Samos M, Bolek T, Skornova I, Stanciakova L, Stasko J, et al. Direct Oral Anticoagulants: Novel Approach for the Treatment of Thrombosis in Pediatric Patients? Pediatr Cardiol 2019; 40(7):1431-1438. doi: 10.1007/s00246-019-02159-3 Yu X, Zhu W, Liu C, Lu R. Direct Oral Anticoagulants for Treating Acute Venous Thromboembolism in Children: Meta-Analysis of Randomized Controlled Trials. Clin Appl Thromb Hemost 2024; 30:10760296241271386. doi: 10.1177/10760296241271386 Alqahtani S, Gibbs KD, Montanez NA, Krause KJ, van Ommen CH, Srivaths LV. Direct oral anticoagulant therapy in adolescent venous thromboembolism: A systematic review. Pediatr Blood Cancer 2024; 71(9):e31131. doi: 10.1002/pbc.31131 Cao Z, Fu Z, Liu Y, Liu T, Zhan M, Liu X, et al. Probable rivaroxaban-induced erythema multiforme in children: A case report. Saudi Pharm J 2023; 31(11):101801. doi: 10.1016/j.jsps.2023.101801 Spiezia L, Campello E, Tormene D, Simioni P. Venous Thromboembolism in Children: The Rivaroxaban Experience. Semin Thromb Hemost 2024; 50(6):866-872. doi: 10.1055/s-0043-1778106 Bhat RV, Young G, Sharathkumar AA. How I treat pediatric venous thromboembolism in the DOAC era. Blood 2024; 143(5):389-403. doi: 10.1182/blood.2022018966 van Ommen CH, Albisetti M, Chan AK, Estepp J, Jaffray J, Kenet G, et al. The Edoxaban Hokusai VTE PEDIATRICS Study: An open-label, multicenter, randomized study of edoxaban for pediatric venous thromboembolic disease. Res Pract Thromb Haemost 2020; 4(5):886-892. doi: 10.1002/rth2.12352 FDA Approved Drug Products: Xarelto (rivaroxaban) tablets/suspension for oral administration (February 2023). https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022406s041lbl.pdf George C, Rahman M, Monagle P. Challenges and Opportunities in the Pharmacological Treatment of Acute Venous Thromboembolism in Children. Paediatr Drugs 2020; 22(4):385-397. doi: 10.1007/s40272-020-00403-5 DrugBank. . FDA’s Orange Book. . Medical Dictionary for Regulatory Activities. . Investigators E, Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363(26):2499-2510. doi: 10.1056/NEJMoa1007903 Male C, Lensing AWA, Palumbo JS, Kumar R, Nurmeev I, Hege K, et al. Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial. Lancet Haematol 2020; 7(1):e18-e27. doi: 10.1016/S2352-3026(19)30219-4 Jacobson-Kelly AE, Samuelson Bannow BT. Abnormal uterine bleeding in users of rivaroxaban and apixaban. Hematology Am Soc Hematol Educ Program 2020; 2020(1):538-541. doi: 10.1182/hematology.2020000166 Monagle P, Lensing AWA, Thelen K, Martinelli I, Male C, Santamaria A, et al. Bodyweight-adjusted rivaroxaban for children with venous thromboembolism (EINSTEIN-Jr): results from three multicentre, single-arm, phase 2 studies. Lancet Haematol 2019; 6(10):e500-e509. doi: 10.1016/S2352-3026(19)30161-9 Qian Y, Zhao X, Liu D, Liu J, Yue Z, Liu W. Adverse events of direct factor Xa inhibitors: a disproportionality analysis of the FAERS database. Expert Opin Drug Saf 2024:1-10. doi: 10.1080/14740338.2024.2368815 Alshammari TM, Ata SI, Mahmoud MA, Alhawassi TM, Aljadhey HS. Signals of bleeding among direct-acting oral anticoagulant users compared to those among warfarin users: analyses of the post-marketing FDA Adverse Event Reporting System (FAERS) database, 2010-2015. Ther Clin Risk Manag 2018; 14:803-809. doi: 10.2147/TCRM.S161148 Nathan KT, Conn KM, van Manen RP, Brown JE. Signal detection for bleeding associated with the use of direct oral anticoagulants. Am J Health Syst Pharm 2018; 75(13):973-977. doi: 10.2146/ajhp170529 Raschi E, Poluzzi E, Koci A, Salvo F, Pariente A, Biselli M, et al. Liver injury with novel oral anticoagulants: assessing post-marketing reports in the US Food and Drug Administration adverse event reporting system. Br J Clin Pharmacol 2015; 80(2):285-293. doi: 10.1111/bcp.12611 Cicione A, Lombardo R, Gallo G, Guidotti A, Zammitti F, Ghezzo N, et al. Medications mostly associated with hematuria: assessment of the EudraVigilance and Food and Drug Administration pharmacovigilance databases entries. Minerva Urol Nephrol 2024; 76(1):68-73. doi: 10.23736/S2724-6051.22.05018-2 Wu J, Wu J, Tang B, Wang X, Wei F, Zhang Y, et al. Suspected adverse drug reactions of rivaroxaban reported in the United States food and drug administration adverse event reporting system database: a pharmacovigilance study. Front Pharmacol 2024; 15:1399172. doi: 10.3389/fphar.2024.1399172 Ly S, Naman A, Chaufour-Higel B, Patey M, Arndt C, Delemer B, et al. Pituitary apoplexy and rivaroxaban. Pituitary 2017; 20(6):709-710. doi: 10.1007/s11102-017-0828-4 Andrew M. Developmental hemostasis: relevance to thromboembolic complications in pediatric patients. Thromb Haemost 1995; 74(1):415-425. doi: Yee DL, O'Brien SH, Young G. Pharmacokinetics and pharmacodynamics of anticoagulants in paediatric patients. Clin Pharmacokinet 2013; 52(11):967-980. doi: 10.1007/s40262-013-0094-1 Monagle P, Barnes C, Ignjatovic V, Furmedge J, Newall F, Chan A, et al. Developmental haemostasis. Impact for clinical haemostasis laboratories. Thromb Haemost 2006; 95(2):362-372. doi: 10.1160/TH05-01-0047 Additional Declarations No competing interests reported. Supplementary Files supplementarymaterials.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5713066","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":396074657,"identity":"371cf566-a929-4c79-a358-57ea813fe8ae","order_by":0,"name":"Guimu Guo","email":"","orcid":"","institution":"Fujian Maternity and Child Health Hospital, Fujian Medical University","correspondingAuthor":false,"prefix":"","firstName":"Guimu","middleName":"","lastName":"Guo","suffix":""},{"id":396074658,"identity":"9f40597e-92af-4022-ab8e-8d62da9a3a08","order_by":1,"name":"Tingting Chen","email":"","orcid":"","institution":"Fujian Maternity and Child Health Hospital, Fujian Medical University","correspondingAuthor":false,"prefix":"","firstName":"Tingting","middleName":"","lastName":"Chen","suffix":""},{"id":396074660,"identity":"c7648e4f-29e6-4772-be4c-27cd314c919c","order_by":2,"name":"Lingling Ye","email":"","orcid":"","institution":"Fujian Maternity and Child Health Hospital, Fujian Medical University","correspondingAuthor":false,"prefix":"","firstName":"Lingling","middleName":"","lastName":"Ye","suffix":""},{"id":396074661,"identity":"ce0cec73-e295-4537-a360-04768156786a","order_by":3,"name":"Jintuo Zhou","email":"","orcid":"","institution":"Fujian Maternity and Child Health Hospital, Fujian Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jintuo","middleName":"","lastName":"Zhou","suffix":""},{"id":396074662,"identity":"3218f31a-51f9-4cc5-b268-14561f098bb5","order_by":4,"name":"Jinhua Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABB0lEQVRIiWNgGAWjYFAC5sYDDAwHQIwDBxIqbHj42RsIaWFsgGphS3zw4UyajGTPAaK18Bgbzmw5bGNwwwG/BnP2xobDPH/uyJvzLzCT5m04z8Nwg4Hxw8cc3Fosew4CtfA8M9w540GaNO+O2zyMsxuYJWduw63F4EYiUIvEYcYNNw4ck+Y9c5uHWeYAGzMvQS0Gh+033DjYJs3bdo6HTSKBGC0JhxM3nG9mNpzZdoCHh5AWkF8OzjlwOHnDDTZGYCAn80jwHGzG6xdz9uaDD978OWy74fz5D8CotLO3P9588MNHfA4DYiYeEEsiASbG2IBbPVQL4w8Qi/8AXoWjYBSMglEwggEAoSNjZcVYQu0AAAAASUVORK5CYII=","orcid":"","institution":"Fujian Maternity and Child Health Hospital, Fujian Medical University","correspondingAuthor":true,"prefix":"","firstName":"Jinhua","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2024-12-26 01:53:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5713066/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5713066/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":72738813,"identity":"894b9b4e-bfe3-46d0-90ce-7d1b8f4a7def","added_by":"auto","created_at":"2025-01-01 09:16:17","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":157605,"visible":true,"origin":"","legend":"\u003cp\u003eThe Flow charts of AEs associated with NOACs in the overall and pediatric populations obtained from the FAERS database. BCPNN, bayesian confidence propagation neural network; CI, confidence interval; EBGM, empirical bayesian geometric mean; IC, information component; PRR, proportional reporting ratio; ROR, reporting odds ratio; NOACs, novel oral anticoagulants.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5713066/v1/70d44f1ebd0496884f999651.png"},{"id":72738810,"identity":"e6e854cd-cd0a-42f0-876f-49450ef9f5d5","added_by":"auto","created_at":"2025-01-01 09:16:17","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":243097,"visible":true,"origin":"","legend":"\u003cp\u003eTime to onset of adverse events associated with NOACs in the overall population (A) and the pediatric population (B) from the US Food and Drug Administration Adverse Event Reporting System database. Gray, the case number in the corresponding onset period; Black dots, the cumulative percentage of cases in the corresponding time period; Left ordinate: the number of cases; Right ordinate, the cumulative percentage; Abscissa: time to onset.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-5713066/v1/66c4e93e54b17062fd892bcb.png"},{"id":101951464,"identity":"a9ae0881-4357-428f-a373-f53215227263","added_by":"auto","created_at":"2026-02-05 10:43:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2013498,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5713066/v1/5e1bc19f-8579-432d-ad46-9dc4e2bcc147.pdf"},{"id":72738809,"identity":"0a9c117b-a892-44bc-a8cb-220ae641e7de","added_by":"auto","created_at":"2025-01-01 09:16:17","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":28778,"visible":true,"origin":"","legend":"","description":"","filename":"supplementarymaterials.docx","url":"https://assets-eu.researchsquare.com/files/rs-5713066/v1/c69edd220e2cf4631c14e4f4.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eA disproportionate analysis of novel oral anticoagulants in the overall and pediatric populations: a pharmacovigilance study based on FDA Adverse Event Reporting System database\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"1 Introduce","content":"\u003cp\u003eVenous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, is a common thrombotic disorder in pediatrics, especially in hospitalized children \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. In recent years, its incidence has continued to rise \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Anticoagulants conventionally used to treat VTE include vitamin K antagonists (VKAs), unfractionated heparin (UFH), and low molecular weight heparins (LMWHs) \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Although heparin and warfarin are cost-effective and highly efficacious, their use involves certain risks and limitations. For example, heparin may cause fatal heparin-induced thrombocytopenia and osteoporosis, while warfarin presents challenges such as a narrow therapeutic window, the need for frequent monitoring of anticoagulant activity, sensitivity to dietary and drug interactions, and complex dosage adjustments, limiting their clinical application \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Novel oral anticoagulants (NOACs), including direct factor Xa inhibitors\u0026mdash;rivaroxaban, apixaban, and edoxaban\u0026mdash;and the direct thrombin inhibitor, dabigatran, has revolutionized the management of VTE. These agents offer several advantages over traditional anticoagulants, like convenient oral administration, predictable pharmacokinetics, simplified treatment regimens, minimal interactions with food and drugs, immediate onset of therapeutic action, obviating the need for routine anticoagulant monitoring, and a reduced risk of hemorrhagic events \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. Consequently, NOACs are increasingly favored over VKAs and are extensively utilized in adult populations for the prevention and treatment of conditions including stroke, deep vein thrombosis and pulmonary embolism. Given the scope of these developments, NOACs represent a promising alternative in the pediatric setting.\u003c/p\u003e \u003cp\u003eCurrently, NOACs have garnered approval for the management of pediatric VTE \u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. In December 2021, the US Food and Drug Administration (FDA) approved rivaroxaban and dabigatran for the treatment of pediatric patients, marking a significant advancement in therapeutic options \u003csup\u003e[\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. The completion of the HOKUSAI-Jr Phase III study of edoxaban in children and the ongoing CANINES Phase IV trial of apixaban in children with venous thromboembolism \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e, imply a potential broadening of the anticoagulant spectrum for pediatric applications. Beyond the scope of VTE treatment, NOACs are under investigation for the prophylactic potential in pediatric populations with congenital and acquired heart diseases, as well as in oncological settings \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eFor pediatric patients, adverse drug reactions are generally mild to moderate. Contrasting with adults, pediatric patients more frequently report symptoms such as headache, fever, epistaxis, vomiting, and tachycardia, alongside elevated levels of total and conjugated bilirubin. The incidence of menorrhagia in adolescent women after menarche is similar to that in adults \u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. Thrombocytopenia, observed in adult postmarket experience, is similarly observed in pediatric clinical studies. Additionally, there have been some rare reports of adverse reactions, such as Cao Z et al., who reported erythema multiforme in a pediatric patient with antiphospholipid syndrome (APS) after rivaroxaban treatment \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eChildren exhibit significantly mature differences from adults in terms of hemostatic systems and pharmacokinetic parameters, presenting unique age-dependent characteristics. However, the use of NOACs in children largely relies on extrapolation from adult data, resulting in extremely limited experience in pediatric clinical practice \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. There is a pressing need for more large-scale clinical trials to validate the safety and efficacy of these drugs in pediatric patients. Therefore, this study utilizes the FDA Adverse Event Reporting System (FAERS) database to analyze the actual adverse event (AE) signals of NOACs in the overall population and pediatric patients. Specifically, the discovery of related AE signals in the pediatric population is intended to raise awareness among clinicians regarding the use of NOACs in treating pediatric patients, reduce the occurrence of adverse reactions, and ensure the safety of NOACs.\u003c/p\u003e"},{"header":"2 Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Data sources and study design\u003c/h2\u003e \u003cp\u003eThe FAERS database (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://fs.fda.gov/extensions/FPDQDE-FAERS/FPD-QDE-FAERS.html\u003c/span\u003e\u003cspan address=\"https://fs.fda.gov/extensions/FPDQDE-FAERS/FPD-QDE-FAERS.html\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) includes over 15\u0026nbsp;million reports from more than 100 countries, with the majority originating from the United States, making it one of the largest pharmacovigilance databases in the world. The FAERS database contains information such as the demographics, clinical indications, treatment regimens, adverse events, treatment start date, and the event date. The reports in FAERS database are primarily submitted by consumers, healthcare professionals, and manufacturers. The FAERS database provides researchers with raw data for the analysis of drugs and adverse reactions. FAERS database is globally recognized as a critical reporting system and its official data can be downloaded for free from the Food and Drug Administration (FDA) website.\u003c/p\u003e \u003cp\u003eThis study obtained individual case reports on AEs related to NOACs from the FAERS database, covering from the third quarter of 2014 to the first quarter of 2024 in the overall population, and conducted a comprehensive disproportionate analysis. Based on the FAERS database, a total of 35,706,802 adverse event reports were collected, among which 1,374,645 reports were from the pediatric population. Out of all the reports, 554,605 were associated with NOACs. By excluding patients older than 18 years of age, as well as those records missing age or age_cod information, a final total of 820 adverse event reports related to NOACs in children were identified.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Pharmacovigilance Data Extraction and Analysis\u003c/h2\u003e \u003cp\u003eUsing Navicat software (version 16; Hong Kong Z-Rays Digital Technology Limited; China) extracted the raw data from the FAERS database. Each quarterly ASCII data update in the FAERS database includes 7 sub-files, namely: DEMO, REAC, DRUG, OUTC, RPSR, THER, and INDI. The primaryid, a unique identifier for FAERS reports, facilitated the removal of duplicate records to ensure only the most updated versions were retained, with a specification that the report must denote the drug as the Primary Suspect (PS). Considering that duplicate or implausible reports can lead to serious errors, an extensive cleanup of the drug tables was initially performed each quarter, followed by a vertical merger of the 7 sub-files from each quarter into a master table. The DEMO and DRUG tables were deduplicated again to ensure a unique primaryid, thus guaranteeing that the final dataset did not contain duplicate reports. Finally, based on the unique primaryid, the INDI, REAC, RPSR, and THER tables were mapped to filter corresponding report events. The detailed processing steps of the FAERS database are illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn this study, the names and commercial brands of the NOACs were identified through the FDA\u0026rsquo;s Orange Book and DrugBank as Rivaroxaban (Xarelto), Apixaban (Eliquis), Edoxaban (Lixiana, Savaysa), and Dabigatran (Pradaxa) \u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. The names of the adverse drug reactions (ADRs) were standardized using the Medical Dictionary for Regulatory Activities (MedDRA, version 26) \u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. According to MedDRA, the ADRs were coded as Preferred Terms (PTs) and corresponding System Organ Class (SOC) categories were listed to facilitate the comparison of potential signal strengths at the same level.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Descriptive analysis\u003c/h2\u003e \u003cp\u003eIn the reports related to Rivaroxaban, Apixaban, Edoxaban, and Dabigatran, patient demographic characteristics (gender, age, and type of report) and clinical aspects (time onset and outcomes of the adverse events) were recorded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Disproportionality analysis\u003c/h2\u003e \u003cp\u003eCurrently, various national spontaneous reporting centers and the Uppsala Monitoring Centre employ a disproportionate analysis to identify potential signals between drugs and adverse events. This study evaluates the correlation between drugs and AEs using a 2 \u0026times; 2 contingency table (see \u003cb\u003eSupplemental Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e\u003c/b\u003e) and employs multiple methods to detect signals, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM). The formulas for disproportionate analysis for signal detection as shown in \u003cb\u003eSupplemental Table S2\u003c/b\u003e. Signals of AE are identified using set thresholds: a\u0026thinsp;\u0026ge;\u0026thinsp;3, the lower bound of the 95% confidence interval of ROR greater than 1, PRR\u0026thinsp;\u0026ge;\u0026thinsp;2, IC025\u0026gt;0, EBGM05\u0026gt;2. Higher values of ROR, PRR, BCPNN, and EBGM indicate stronger AE signals, suggesting a stronger statistical relationship between the target drug and target AE. All data processing and analysis were calculated by excel software and plotted by origin (2021 version).\u003c/p\u003e \u003c/div\u003e"},{"header":"3 Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Descriptive analysis\u003c/h2\u003e \u003cp\u003eFrom the third quarter of 2014 to the first quarter of 2024, the FAERS database detected AE reports related to Rivaroxaban, Apixaban, Edoxaban, and Dabigatran in the overall population as 228,621 (41.22%), 237,489 (42.82%), 12,589 (2.27%), and 76,806 (13.85%) respectively, and in the pediatric population as 476 (58.05%), 241 (29.39%), 5 (0.61%), and 98 (11.95%) respectively. Basic characteristics of the reported patients can be seen in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of adverse events reports associated with novel oral anticoagulants.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCategories\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNOACs used in\u003c/p\u003e \u003cp\u003ethe overall\u003c/p\u003e \u003cp\u003ePopulation, N (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNOACs used in\u003c/p\u003e \u003cp\u003ethe pediatric\u003c/p\u003e \u003cp\u003ePopulation, N (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReported case\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e554605\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e820\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e264278 (47.65%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e413 (50.37%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e249588 (45.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e361 (44.02%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown or missing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40715 (7.35%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46 (5.61%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReport year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24223 (4.37%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41 (5.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58941 (10.63%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43 (5.24%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64425 (11.62%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87 (10.61%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65405 (11.79%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71 (8.66%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62541 (11.28%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e94 (11.46%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63831 (11.51%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62 (7.56%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73798 (13.31%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e123 (15.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50699 (9.14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65 (7.93%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46581 (8.40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e130 (15.85%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35618 (6.42%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70 (8.54%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8120 (1.46%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (4.15%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown or missing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e423 (0.08%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReporter country\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnited States\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e358102 (64.57%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e386 (47.07%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGermany\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33880 (6.11%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71 (8.66%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGreat Britain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17434 (3.14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (3.54%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFrance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16971 (3.06%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64 (7.80%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e128218 (23.11%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e270 (32.92%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReporter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConsumer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e304234 (54.86%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e223 (27.20%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysician\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e142410 (25.68%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e297 (36.22%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePharmacist\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72600 (13.09%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e205(25.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther health-professional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30674 (5.53%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e88 (10.73%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLawyer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1624 (0.29%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (0.49%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emissing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3063 (0.55%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (0.37%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndication (top 5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProduct used for unknown indication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e179005(32.28%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e259(31.59%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtrial fibrillation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e118522(21.37%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53(6.46%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebrovascular accident prophylaxis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e112732(20.33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeep vein thrombosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39076(7.05%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e102(12.44%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulmonary embolism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23920(4.31%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThrombosis prophylaxis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87(10.61%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmbolism venous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44(5.37%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcomes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeath\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42984 (14.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (5.22%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLife-threatening\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10617 (3.58%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (4.93%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospitalization\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e102676 (34.61%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e135 (39.13%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisability\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4507 (1.52%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (2.03%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther serious illness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e135202 (45.57%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e158 (45.80%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCongenital Anomaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76 (0.02%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (2.32%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRequired Intervention to Prevent Permanent Impairment/Damage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e633 (0.21%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (0.58%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdverse event occurrence time, days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (Q1, Q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14(1.75,52.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71(11.50,307.50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNotably, female (overall population: 47.65%, pediatric patients: 50.37%) reported AEs more than males (overall population: 45%, pediatric patients: 44.02%). In the overall population, the highest reporting rate was from 2016\u0026ndash;2020, while a declining trend in reports has been observed in recent years. For pediatric patients, the peak reporting year was 2022, accounting for 15.85% of reports. The majority of reports were submitted by medical professionals (overall population: 44.3%, pediatric patients: 71.95%) and predominantly from the United States (overall population: 64.57%, pediatric patients: 47.07%). In the overall population, NOACs were primarily used for Product used for unknown indication (32.28%), Atrial fibrillation (21.37%), and Cerebrovascular accident prophylaxis (20.33%). In the pediatric population, the main indication was for Product used for unknown indication (31.59%), Deep vein thrombosis (12.44%), and Thrombosis prophylaxis (12.44%). The median time to onset of AEs was 71 days in the overall population and 14 days in pediatric patients (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), with the primary outcomes being other serious illnesses (overall population: 45.57%, pediatric patients: 45.80%) and hospitalization (overall population: 34.61%, pediatric patients: 39.13%).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Signals detection associated with NOACs in the overall population\u003c/h2\u003e \u003cp\u003eThis study systematically analyzed the AE signals associated with NOACs across different SOCs in the overall population (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. The analysis encompassed 26 SOCs, with Gastrointestinal disorders (10.37%), Nervous system disorders (9.14%), and Vascular disorders (6.84%) emerging as the most frequently reported. Ranked by ROR, the SOC categories that exhibited the most significant AE signal strengths were Congenital, familial, and genetic disorders (n\u0026thinsp;=\u0026thinsp;842, ROR [95% CI]: 40.71 [37.33;44.39], PRR [95% CI]: 40.65 [37.28;44.32], IC [IC025]: 4.63 [4.52], EBGM [EBGM05]: 25.16 [2.96]), Endocrine disorders (n\u0026thinsp;=\u0026thinsp;188, ROR [95% CI]: 24.23 [20.48;28.66], PRR [95% CI]: 24.22 [20.47;28.65], IC [IC025]: 4.09 [3.85], EBGM [EBGM05]: 17.8 [2.43]), and Gastrointestinal disorders (n\u0026thinsp;=\u0026thinsp;57477, ROR [95% CI]: 14.08 [13.95;14.22], PRR [95% CI]: 12.73 [12.62;12.84], IC [IC025]: 3.43 [3.41], EBGM [EBGM05]: 10.77 [2.35]).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAdverse event signals in various system organ classes for NOACs used in the overall and pediatric population.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSystem organ class\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase number\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFrequency (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eROR\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePRR\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIC (IC025)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eEBGM (EBGM05)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eNOACs used in the overall population\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003egastrointestinal disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57477\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.36%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.08(13.95;14.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.73(12.62;12.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.43(3.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e10.77(2.35)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003enervous system disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50670\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.14%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.37(5.32;5.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.97(4.93;5.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.23(2.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.68(1.53)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003evascular disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37956\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.84%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.64(9.54;9.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.05(8.96;9.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.01(2.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8.04(2.06)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003einjury, poisoning and procedural complications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36984\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.67%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.21(3.17;3.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.06(3.03;3.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.57(1.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.97(1.08)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003egeneral disorders and administration site conditions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33965\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.12%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.36(2.33;2.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.27(2.25;2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.16(1.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.23(0.79)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecardiac disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27124\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.89%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.66(3.62;3.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.53(3.49;3.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.76(1.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.4(1.21)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003erespiratory, thoracic and mediastinal disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21571\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.89%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.58(4.51;4.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.44(4.38;4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.07(2.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.21(1.42)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003erenal and urinary disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16774\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.02%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.3(3.25;3.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.23(3.18;3.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.64(1.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.13(1.12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eblood and lymphatic system disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14072\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.54%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.38(4.3;4.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.29(4.22;4.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.03(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.08(1.38)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003einvestigations\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10572\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.91%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.46(4.37;4.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.39(4.31;4.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.06(2.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.17(1.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003esurgical and medical procedures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9876\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.78%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.24(3.18;3.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.2(3.14;3.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.63(1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.1(1.11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ereproductive system and breast disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4440\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.80%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.28(5.12;5.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.25(5.09;5.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.3(2.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.92(1.55)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eneoplasms benign, malignant and unspecified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4127\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.74%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.62(2.54;2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.61(2.53;2.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.35(1.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.54(0.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emusculoskeletal and connective tissue disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3986\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.72%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.35(2.28;2.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.34(2.27;2.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.2(1.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.3(0.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eskin and subcutaneous tissue disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3482\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.63%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.52(2.43;2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.51(2.42;2.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.29(1.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.45(0.87)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eeye disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3340\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.60%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.3(2.22;2.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.29(2.21;2.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.17(1.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.25(0.78)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eear and labyrinth disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2132\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.38%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.14(3.01;3.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.13(3;3.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.6(1.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.03(1.06)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003einfections and infestations\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1930\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.35%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.79(1.71;1.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.78(1.7;1.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.82(0.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.76(0.54)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emetabolism and nutrition disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1562\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.28%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.54(1.47;1.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.54(1.47;1.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.61(0.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.53(0.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eproduct issues\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1081\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.91(2.74;3.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.91(2.73;3.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.5(1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.82(0.98)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ehepatobiliary disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1034\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.19%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.7(1.6;1.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.7(1.59;1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.75(0.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.68(0.49)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003econgenital, familial and genetic disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e842\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.15%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40.71(37.33;44.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40.65(37.28;44.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.63(4.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e25.16(2.96)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003esocial circumstances\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e314\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.06%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.5(1.34;1.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.5(1.34;1.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.57(0.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.49(0.35)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eendocrine disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e188\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.03%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.23(20.48;28.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24.22(20.47;28.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.09(3.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e17.8(2.43)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eimmune system disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e164\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.03%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.54(3.02;4.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.54(3.02;4.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.76(1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.4(1.05)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epregnancy, puerperium and perinatal conditions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.6(2.63;16.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.6(2.63;16.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.06(0.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.07(0.72)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eNOACs used in the pediatric population\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003erenal and urinary disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.10%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.91(11.31;42.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21.68(11.27;41.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.2(3.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e21.42(1.58)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003einvestigations\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.17%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.28(8.3;18.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.92(8.16;17.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.5(4.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e11.85(1.67)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ehepatobiliary disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.16(3.26;31.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.13(3.26;31.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.77(0.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e10.07(0.74)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003evascular disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.90%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.93(7.02;11.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.22(6.6;10.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.45(6.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8.19(1.65)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ereproductive system and breast disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.34%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.58(4.18;13.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.5(4.16;13.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.37(3.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7.47(1.11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eskin and subcutaneous tissue disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.61%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.07(2.51;14.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.04(2.51;14.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.37(1.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.02(0.74)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003erespiratory, thoracic and mediastinal disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.41%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.04(3.45;7.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.9(3.4;7.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.31(4.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.89(1.09)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epregnancy, puerperium and perinatal conditions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.28(1.37;13.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.26(1.38;13.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.73(0.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.26(0.47)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epsychiatric disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.46%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.49(1.98;6.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.46(1.97;6.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.3(3.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.45(0.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emusculoskeletal and connective tissue disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.73%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.45(1.55;7.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.44(1.55;7.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.52(2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.43(0.55)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003einjury, poisoning and procedural complications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e172\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.98%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.87(2.42;3.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.47(2.17;2.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.76(5.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.47(0.76)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003esurgical and medical procedures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.49%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.78(1.04;7.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.77(1.04;7.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.02(1.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.77(0.38)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003enervous system disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.29%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.51(1.71;3.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.46(1.7;3.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.9(4.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.46(0.61)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003egeneral disorders and administration site conditions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.22%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.17(1.16;4.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.16(1.17;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.95(2.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.16(0.41)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003einfections and infestations\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.97(0.63;6.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.97(0.64;6.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.65(0.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.97(0.22)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003egastrointestinal disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.17%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.63(1.1;2.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.61(1.1;2.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.56(3.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.61(0.32)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eAbbreviations: BCPNN, bayesian confidence propagation neural network; CI, confidence interval; EBGM, empirical bayesian geometric mean; IC, information component; PRR, proportional reporting ratio; ROR, reporting odds ratio; NOACs, novel oral anticoagulants.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe detailed analyses revealed the top 50 PTs for NOACs-associated AEs in the overall population, as summarized in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Predominantly, the five most frequently PTs related to NOACs included Gastrointestinal hemorrhage (3.97%), Internal hemorrhage (0.67%), Lower gastrointestinal hemorrhage (0.45%), Hemorrhagic anemia (0.24%), and Embolic stroke (0.17%). Further analysis focused on the PTs exhibiting the strongest AE signal strengths sorted by ROR, including Procoagulant therapy (n\u0026thinsp;=\u0026thinsp;740, ROR[95% CI]: 9393.13[3898.06;22634.54], PRR[95% CI]:9380.6[3892.89;22604.17], IC [IC025]:5.94[5.82], EBGM [EBGM05]:63.95[1.73]), Coagulation factor X level increased (n\u0026thinsp;=\u0026thinsp;13, ROR[95% CI]༚823.99[107.79;6299.02], PRR[95% CI]:823.97[107.79;6298.85], IC [IC025]:4.23[3.3], EBGM [EBGM05]:59.78[0.54]), Spinal haematoma (n\u0026thinsp;=\u0026thinsp;4, ROR[95% CI]༚253.53[28.34;2268.41], PRR[95% CI]:253.53[28.34;2268.39], IC [IC025]:2.96[1.2], EBGM [EBGM05]:51.51[0.44]), Thrombin time (n\u0026thinsp;=\u0026thinsp;4, ROR[95% CI]༚253.53[28.34;2268.41], PRR[95% CI]:253.53[28.34;2268.39], IC [IC025]:2.96[1.2], EBGM [EBGM05]:51.51[0.44]), and Anti factor X antibody positive (n\u0026thinsp;=\u0026thinsp;6, ROR[95% CI]༚190.15[38.39;942.13], PRR[95% CI]:190.15[38.38;942.12], IC [IC025]:3.38[1.97], EBGM [EBGM05]:48.29[0.78]). This study also unveiled unexpected AEs, including Cephalohematoma, Hematotympanum, Neoplasm malignant, Pituitary hemorrhage, and Pituitary apoplexy, alongside Antiphospholipid antibodies.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAdverse event signals in top 50 for NOACs used in the overall population.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreferred Terms\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase number\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFrequency (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eROR\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePRR\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIC (IC025)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eEBGM (EBGM05)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProcoagulant therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e740\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.13%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9393.13(3898.06;22634.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9380.6(3892.89;22604.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.94(5.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e63.95(1.73)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoagulation factor X level increased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e823.99(107.79;6299.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e823.97(107.79;6298.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.23(3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e59.78(0.54)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpinal haematoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e253.53(28.34;2268.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e253.53(28.34;2268.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.96(1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e51.51(0.44)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThrombin time\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e253.53(28.34;2268.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e253.53(28.34;2268.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.96(1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e51.51(0.44)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti factor X antibody positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e190.15(38.39;942.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e190.15(38.38;942.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.38(1.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e48.29(0.78)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHepatic haemangioma rupture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e158.46(30.74;816.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e158.46(30.74;816.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.18(1.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e45.99(0.74)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaemorrhagic arteriovenous malformation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e596\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.11%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e135.54(117.58;156.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e135.4(117.46;156.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.4(5.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e43.85(3.28)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClotting factor transfusion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e126.77(43.33;370.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e126.76(43.33;370.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.84(2.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e42.92(1.28)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThrombin time abnormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e118.85(50.39;280.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e118.84(50.39;280.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.18(3.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e41.99(1.58)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThrombin time prolonged\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.01%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e106.68(72.48;157.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e106.67(72.48;156.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.98(4.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e40.39(2.51)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebral ventricular rupture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.02%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e99.05(72.38;135.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e99.04(72.37;135.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.04(4.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e39.26(2.68)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtrial thrombosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e814\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.15%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e96.58(86.59;107.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e96.44(86.47;107.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.25(5.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e38.85(3.28)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCHA2DS2-VASc annual stroke risk high\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e95.07(26.83;336.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e95.07(26.83;336.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.31(1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e38.63(1.03)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFactor Xa activity abnormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e95.07(15.89;569)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e95.07(15.89;569)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.6(0.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e38.63(0.61)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal angiodysplasia haemorrhagic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.01%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e87.44(62.36;122.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e87.42(62.35;122.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.93(4.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e37.32(2.58)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti factor X activity increased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e82.03(43.56;154.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e82.02(43.56;154.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.35(3.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e36.32(1.91)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiverticulum intestinal haemorrhagic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e885\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.16%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e72.87(66.16;80.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e72.75(66.06;80.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.08(4.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e34.41(3.21)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBasal ganglia haemorrhage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e289\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.05%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e64.99(55.15;76.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e64.96(55.13;76.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.95(4.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e32.59(2.96)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuodenal vascular ectasia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e63.38(22.23;180.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e63.38(22.23;180.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.39(2.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e32.19(1.22)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eContraindication to surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e63.38(18.35;218.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e63.38(18.35;218.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.07(1.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e32.19(1.01)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral artery aneurysm rupture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e63.38(15.85;253.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e63.38(15.85;253.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.85(1.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e32.19(0.87)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLower gastrointestinal haemorrhage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2513\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.45%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e61.58(58.29;65.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e61.31(58.04;64.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.98(4.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e31.66(3.27)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaemorrhagic anaemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1305\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.24%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e60.6(56.17;65.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e60.46(56.05;65.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.96(4.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e31.43(3.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnastomotic ulcer haemorrhage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.01%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e59.87(40.83;87.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e59.86(40.83;87.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.6(4.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e31.27(2.35)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThalamus haemorrhage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e285\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.05%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e59.65(50.74;70.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e59.62(50.72;70.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.89(4.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e31.21(2.93)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTraumatic intracranial haematoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e56.34(21.74;146.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e56.34(21.74;146.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.48(2.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e30.3(1.32)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh frequency ablation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e130\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.02%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e53.52(42.37;67.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e53.5(42.37;67.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.73(4.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e29.47(2.68)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtrio-oesophageal fistula\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e52.82(16.12;173.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e52.82(16.12;173.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.04(1.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e29.26(1.03)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic gastrointestinal bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.02%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e51.29(38.79;67.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e51.28(38.78;67.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.64(4.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e28.79(2.54)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePericardial haemorrhage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e600\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.11%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e51.17(45.95;56.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e51.11(45.9;56.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.81(4.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e28.74(3.02)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFailure to suspend medication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.01%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e50.01(36.64;68.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e50(36.63;68.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.57(4.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e28.39(2.45)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal endoscopic therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e48.76(27.22;87.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e48.76(27.22;87.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.08(3.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e27.99(1.86)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmbolic stroke\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e930\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.17%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e48.51(44.54;52.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e48.44(44.47;52.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.78(4.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e27.89(3.06)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal haemorrhage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.97%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e48.5(47.66;49.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e46.62(45.82;47.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.77(4.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e27.29(3.25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmbolic cerebral infarction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e182\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.03%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e48.08(39.65;58.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e48.06(39.64;58.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.69(4.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e27.77(2.74)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaemorrhagic hepatic cyst\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.01%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e47.93(30.06;76.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e47.92(30.06;76.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.28(3.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e27.72(2.08)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal vascular malformation haemorrhagic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e138\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.02%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e47.81(38.33;59.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e47.8(38.32;59.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.66(4.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e27.68(2.66)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProstatic varices\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e47.54(10.64;212.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e47.54(10.64;212.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.52(0.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e27.59(0.74)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost procedural haematuria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.01%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e46.43(32.46;66.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e46.42(32.46;66.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.44(3.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e27.22(2.31)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVentricular drainage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e46.1(24.21;87.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e46.1(24.21;87.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.92(3.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e27.11(1.73)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebral ventricle collapse\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.01%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e45.95(28.49;74.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e45.95(28.49;74.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.23(3.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e27.06(2.04)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdrenal haemorrhage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e134\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.02%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e45.92(36.77;57.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e45.91(36.76;57.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.62(4.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e27.04(2.64)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSubgaleal haematoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.01%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e45.04(31.78;63.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e45.03(31.77;63.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.44(3.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e26.74(2.32)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnticoagulation drug level increased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e106\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.02%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e43.63(34.07;55.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e43.63(34.07;55.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.55(4.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e26.25(2.55)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaematuria traumatic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e42.94(24.68;74.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e42.94(24.67;74.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.04(3.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e26(1.87)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaemorrhagic erosive gastritis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.02%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e42.41(32.62;55.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e42.41(32.61;55.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.51(4.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e25.81(2.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eActivated partial thromboplastin time\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e42.26(15.04;118.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e42.25(15.04;118.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.15(1.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e25.75(1.16)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRussell's viper venom time abnormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e42.26(11.92;149.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e42.25(11.92;149.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.78(1.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e25.75(0.92)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInternal haemorrhage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3725\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.67%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e41.02(39.36;42.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e40.75(39.11;42.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.65(4.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e25.19(3.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMesenteric haemorrhage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e40.5(24;68.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e40.49(24;68.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.05(3.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e25.1(1.91)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eAbbreviations: BCPNN, bayesian confidence propagation neural network; CI, confidence interval; EBGM, empirical bayesian geometric mean; IC, information component; PRR, proportional reporting ratio; ROR, reporting odds ratio; NOACs, novel oral anticoagulants.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Signals detection associated with NOACs in Pediatric Population\u003c/h2\u003e \u003cp\u003eIn the pediatric, the AE signals associated with NOACs were fewer when compared to the overall population, and identified 16 SOCs of AE signals, as delineated in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The SOC categories with the highest frequencies included Injury, poisoning and procedural complications (20.98%), Vascular disorders (8.90%), and Respiratory, thoracic and mediastinal Disorders (3.41%). Ranked by ROR, particularly prominent AE signal strengths were found in the SOCs of Renal and urinary disorders (n\u0026thinsp;=\u0026thinsp;9, ROR [95% CI]: 21.91[11.31;42.44], PRR [95% CI]: 21.68[11.27;41.69], IC [IC025]: 4.2[3.06], EBGM [EBGM05]: 21.42[1.58]), Investigations (n\u0026thinsp;=\u0026thinsp;26, ROR [95% CI]: 12.28[8.3;18.17], PRR [95% CI]: 11.92[8.16;17.43], IC [IC025]: 5.5[4.85], EBGM [EBGM05]: 11.85[1.67]), and Hepatobiliary disorders (n\u0026thinsp;=\u0026thinsp;3, ROR [95% CI]: 10.16[3.26;31.67], PRR [95% CI]: 10.13[3.26;31.44], IC [IC025]: 2.77[0.71], EBGM [EBGM05]: 10.07[0.74]).\u003c/p\u003e \u003cp\u003eThis study identified the top 50 PTs signals associated with NOACs in the pediatric population, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. The five most frequently PTs related to NOACs were Accidental exposure to product by child (3.54%), Deep vein thrombosis (2.93%), Product use issue (2.07%), Intentional overdose (1.71%), and Thrombosis (1.59%). The PTs exhibiting highest signal strength in the pediatric population sorted by ROR, including Haemorrhoidal haemorrhage (n\u0026thinsp;=\u0026thinsp;3, ROR [95% CI]: 1008.19[240.54;4225.69], PRR [95% CI]: 1004.51[240.45;4196.45], IC [IC025]: 2.81[0.74], EBGM [EBGM05]: 628.19[1.54]), Pelvic venous thrombosis (n\u0026thinsp;=\u0026thinsp;3, ROR [95% CI]: 240.04[71.46;806.33], PRR [95% CI]: 239.17[71.48;800.28], IC [IC025]: 2.81[0.74], EBGM [EBGM05]:209.4[1.59]), Thrombophlebitis (n\u0026thinsp;=\u0026thinsp;3, ROR [95% CI]: 129.25[39.86;419.09], PRR [95% CI]: 128.78[39.88;415.9], IC [IC025]: 2.8[0.74], EBGM [EBGM05]: 119.66[1.48]), Deep vein thrombosis (n\u0026thinsp;=\u0026thinsp;24, ROR [95% CI]: 126.94[83.38;193.26], PRR [95% CI]: 123.25[81.89;185.51], IC [IC025]: 5.59[4.91], EBGM [EBGM05]: 114.87[3.12]), and Activated partial thromboplastin time prolonged (n\u0026thinsp;=\u0026thinsp;6, ROR [95% CI]: 70.76[31.17;160.6], PRR [95% CI]: 70.25[31.13;158.52], IC [IC025]: 3.69[2.28], EBGM [EBGM05]: 67.46[1.86]). This study had also found unexpected AE signals in pediatric patients such as Low birth weight baby, Suicide attempt, Intentional self-injury, Foetal exposure during pregnancy, and Alopecia.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAdverse event signals in top 50 for NOACs used in the pediatric population.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreferred Terms\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase number\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFrequency (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eROR\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePRR\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIC (IC025)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eEBGM (EBGM05)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaemorrhoidal haemorrhage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1008.19(240.54;4225.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1004.51(240.45;4196.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.81(0.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e628.19(1.54)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePelvic venous thrombosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e240.04(71.46;806.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e239.17(71.48;800.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.81(0.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e209.4(1.59)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThrombophlebitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e129.25(39.86;419.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e128.78(39.88;415.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.8(0.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e119.66(1.48)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeep vein thrombosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.93%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e126.94(83.38;193.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e123.25(81.89;185.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.59(4.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e114.87(3.12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eActivated partial thromboplastin time prolonged\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.73%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e70.76(31.17;160.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e70.25(31.13;158.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.69(2.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e67.46(1.86)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProthrombin time prolonged\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.73%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e68.83(30.34;156.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e68.33(30.29;154.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.69(2.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e65.69(1.84)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIschaemic stroke\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e48.47(15.35;153.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e48.29(15.36;151.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.8(0.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e46.97(1.22)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThrombosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.59%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e48.27(27.69;84.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e47.52(27.5;82.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.72(3.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e46.24(2.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulmonary embolism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.34%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e46.42(25.4;84.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e45.81(25.27;83.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.5(3.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e44.62(2.08)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSkin laceration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e35.5(11.29;111.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e35.37(11.3;110.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.8(0.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e34.66(1.13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInternational normalised ratio increased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.61%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e33.55(13.81;81.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e33.35(13.8;80.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.44(1.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e32.72(1.44)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaematuria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.10%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e21.91(11.31;42.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e21.68(11.27;41.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.2(3.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e21.42(1.58)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMenorrhagia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.98%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e18.96(9.41;38.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e18.78(9.39;37.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.04(2.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e18.59(1.45)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAccidental exposure to product by child\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.54%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e16.88(11.63;24.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e16.31(11.39;23.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.7(5.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e16.17(1.92)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebrovascular accident\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.49%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e16.33(6.08;43.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e16.25(6.09;43.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.14(1.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e16.11(1.04)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal haemorrhage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.73%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13.78(6.15;30.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e13.69(6.15;30.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.65(2.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e13.58(1.16)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaematoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12.44(3.99;38.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e12.4(3.99;38.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.78(0.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e12.32(0.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaemoptysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11.53(3.7;35.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e11.49(3.7;35.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.78(0.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e11.42(0.78)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCholestasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10.16(3.26;31.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10.13(3.26;31.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.77(0.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e10.07(0.74)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiver function test increased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9.84(3.16;30.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9.81(3.16;30.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.77(0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e9.76(0.73)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProduct prescribing issue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8.9(2.86;27.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8.87(2.86;27.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.77(0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e8.83(0.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEpistaxis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.10%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7.19(3.72;13.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.12(3.71;13.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.11(2.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e7.09(1.01)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAccidental exposure to product\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.98%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6.32(3.15;12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.27(3.14;12.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.95(2.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e6.25(0.91)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlopecia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.61%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6.07(2.51;14.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.04(2.51;14.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.37(1.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e6.02(0.74)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeukopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.49%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.72(2.14;15.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.69(2.14;15.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.09(1.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e5.68(0.65)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntentional product use issue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.73%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.47(2.45;12.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.44(2.45;12.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.58(2.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e5.43(0.76)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaemorrhage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.98%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.1(2.54;10.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.06(2.54;10.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.92(2.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e5.05(0.81)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntentional overdose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.71%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.54(2.67;7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.48(2.66;7.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.55(3.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4.47(0.88)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnaemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.85%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.36(2.07;9.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.33(2.07;9.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.74(2.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4.32(0.69)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral swelling\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.31(1.39;13.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.3(1.39;13.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.73(0.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4.29(0.47)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow birth weight baby\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.28(1.37;13.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.26(1.38;13.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.73(0.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4.26(0.47)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuicide attempt\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.10%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.13(2.14;7.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.1(2.14;7.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.02(2.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4.09(0.73)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProduct administered to patient of inappropriate age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.49%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.07(1.52;10.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.06(1.52;10.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.06(1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4.05(0.52)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHepatic enzyme increased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.92(1.26;12.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.91(1.26;12.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.72(0.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3.9(0.44)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrug administered to patient of inappropriate age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.85%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.88(1.84;8.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.86(1.84;8.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.72(2.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3.85(0.64)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaemoglobin decreased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.84(1.23;11.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.83(1.23;11.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.72(0.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3.82(0.43)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePain in extremity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.73%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.45(1.55;7.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.44(1.55;7.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.52(2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3.43(0.55)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProduct dose omission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.25(1.05;10.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.24(1.05;10.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.71(0.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3.24(0.38)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFall\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.49%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.24(1.21;8.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.23(1.22;8.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.04(1.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3.23(0.44)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment noncompliance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.06(0.98;9.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.05(0.99;9.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.7(0.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3.05(0.36)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParaesthesia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.04(0.98;9.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.03(0.98;9.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.7(0.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3.03(0.36)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVaginal haemorrhage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.89(0.93;8.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.88(0.93;8.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.7(0.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.88(0.34)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospitalisation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.49%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.78(1.04;7.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.77(1.04;7.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.02(1.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.77(0.38)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThrombocytopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.49%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.41(0.9;6.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.4(0.9;6.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3(1.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.4(0.33)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntentional self-injury\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.36(0.76;7.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.36(0.76;7.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.67(0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.36(0.28)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntentional product misuse\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.29(0.74;7.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.28(0.74;7.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.67(0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.28(0.27)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWrong technique in product usage process\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.61%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.26(0.94;5.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.25(0.94;5.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.23(1.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.25(0.34)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAccidental overdose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.13(0.69;6.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.13(0.69;6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.66(0.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.13(0.24)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProduct use issue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.07%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2(1.24;3.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.98(1.24;3.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.4(3.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.98(0.42)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOVID-19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.97(0.63;6.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.97(0.64;6.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.65(0.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.97(0.22)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eAbbreviations: BCPNN, bayesian confidence propagation neural network; CI, confidence interval; EBGM, empirical bayesian geometric mean; IC, information component; PRR, proportional reporting ratio; ROR, reporting odds ratio; NOACs, novel oral anticoagulants\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eOverall, a comparative analysis between the pediatric and overall populations reveals distinct differences in the signal strength of AE associated with NOACs. At the SOC level, the pediatric population displays significantly signal strengths in the SOCs pertaining to Reproductive system and breast disorders, Renal and urinary disorders, Skin and subcutaneous tissue disorders, Respiratory, thoracic and mediastinal disorders, Musculoskeletal and connective tissue disorders, Investigations, Infections and infestations, and Hepatobiliary disorders, while the overall population exhibits more pronounced signal strengths in Gastrointestinal disorders, Nervous system disorders, Pregnancy, puerperium and perinatal conditions, General disorders and administration site conditions, Vascular disorders, and Injury, poisoning and procedural complications. Besides, a psychiatric AE signal is mined in the pediatric population, which is not present in the overall population (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eRecently, there has been a trend towards using NOACs for the treatment of VTE in pediatric patients. Yet now, the robustness of data concerning the efficacy and safety of NOACs in pediatric patients remains scant, largely extrapolated from adult clinical trials or derived from observational cohorts. This study undertakes a comprehensive analysis using the FAERS database to systematically compare and evaluate the AE signals associated with NOACs in both the overall and pediatric populations.\u003c/p\u003e \u003cp\u003eIn the investigation of NOACs within the pediatric population, the Diversity trial evaluated the efficacy and safety of traditional anticoagulants versus dabigatran for treating VTE in children under 18 years. This trial reported that 77% of pediatric participants treated with dabigatran experienced adverse events, with no significant variation observed across different age groups. Predominant adverse events included gastrointestinal symptoms (25%), headache (10%), and fever (6%) \u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. Another investigation conducted by Male C et al. assessed the effectiveness and safety of rivaroxaban in pediatric VTE treatment. 70% of pediatric patients reported adverse events subsequent to rivaroxaban administration, with the most frequent including infections (33%), gastrointestinal diseases (31%), respiratory diseases (24%), neurological diseases (24%), injuries, poisonings, and procedural complications (22%), skin and subcutaneous tissue disorders (19%), and musculoskeletal and connective tissue disorders (16%) \u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. Furthermore, the present investigation has elucidated significantly elevated pharmacovigilance signals for Reproductive system and breast disorders, Renal and urinary disorders, Investigations, and Hepatobiliary disorders in the pediatric population compared to the overall population.\u003c/p\u003e \u003cp\u003ePertinent to disorders of the reproductive system and breast in pediatric subjects, prominent pharmacovigilance signals were discerned for menorrhagia and vaginal haemorrhage. Notably, the signal intensity for menorrhagia was markedly elevated in the pediatric cohort (n\u0026thinsp;=\u0026thinsp;8, ROR [95% CI]: 18.96[9.41;38.19], PRR [95% CI]: 18.78[9.39;37.58], IC [IC025]: 4.04[2.83], EBGM [EBGM05]: 18.59[1.45]) in comparison to the overall population (n\u0026thinsp;=\u0026thinsp;1146, ROR [95% CI]: 7.97[7.49;32.67], PRR [95% CI]: 11.13[4.26;32.44], IC [IC025]: 3.77[1.71], EBGM [EBGM05]: 11.07[1.74]), while the signal strength for vaginal haemorrhage demonstrated a lower magnitude in the pediatric cohort (n\u0026thinsp;=\u0026thinsp;3, ROR [95% CI]:2.89[0.93;8.98], PRR [95% CI]: 2.88[0.93;8.92], IC [IC025]: 2.7[0.63], EBGM [EBGM05]: 2.88[0.34]) as compared to the overall population (n\u0026thinsp;=\u0026thinsp;1555, ROR [95% CI]: 4.42[4.2;33.67], PRR [95% CI]: 12.13[5.26;33.44], IC [IC025]: 4.77[2.71], EBGM [EBGM05]: 12.07[2.74]). Recent studies documented a low incidence of major bleeding (MB) or clinically relevant non-major bleeding (CRNMB); however, the occurrence of other types of abnormal uterine bleeding (AUB) ranged from 15.8\u0026ndash;50%. In pediatric trials, 19% of female patients experienced menorrhagia while undergoing treatment with rivaroxaban\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. When broadening the diagnostic criteria to encapsulate conditions, the incidence of AUB significantly escalates. This phenomenon might account for the heightened reported prevalence of AUB in pediatric studies compared to those conducted in adult populations. Additionally, the elevated prevalence of AUB attributed to anovulatory cycles in adolescents may also contribute to this disparity \u003csup\u003e[\u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAt the PT level, findings such as accidental exposure to the product by a child, drug administered to a patient of inappropriate age, product use issues, and off-label use underscore the necessity for meticulous and reasonable application of NOACs in pediatric. Surprisingly, signals for psychiatric disorders, including suicide attempts and intentional self-injury, were detected in pediatric patients, a phenomenon not observed in the overall population, suggesting that healthcare professionals should remain vigilant regarding the potential psychiatric risks associated with NOACs use in children.\u003c/p\u003e \u003cp\u003eIn adult patients, the prevalent adverse reaction with NOACs is bleeding, especially with rivaroxaban, apixaban is associated with elevated incidence and risk of cardiovascular and cerebral events, whereas edoxaban shows more prominent risk in terms of renal and urinary systems \u003csup\u003e[\u003cspan additionalcitationids=\"CR24 CR25 CR26\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. In this study, bleeding signals were frequently present in the overall population, particularly in the gastrointestinal, nervous, and vascular and lymphatic systems (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The AEs signals related to Congenital, familial, and genetic disorders were the strongest in SOC level, and the PTs exhibiting significant signal strength in this SOC level were Haemorrhagic arteriovenous malformation (n\u0026thinsp;=\u0026thinsp;596, ROR[95% CI]: 135.54[117.58;156.25], PRR[95% CI]: 135.40[117.46;156.08], IC [IC025]: 5.40[5.27], EBGM [EBGM05]: 43.85[3.28]) and Gastrointestinal arteriovenous malformation (n\u0026thinsp;=\u0026thinsp;63, ROR[95% CI]: 36.64[26.87;49.96], PRR[95% CI]: 36.63[26.86;49.96], IC [IC025]: 4.32[3.91], EBGM [EBGM05]: 23.58[2.32]). Wu J et al., based on the FAERS database, also identified a high signal strength at the PT level for Haemorrhagic arteriovenous malformations \u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e. This investigation additionally revealed signals of AEs associated with NOACs in overall population, including Cephalhaematoma, Haematotympanum, Malignant Neoplasm, Pituitary apoplexy, and Antiphospholipid antibodies. Despite these AEs not being explicitly mentioned in the package insert, but their occurrence has been documented in clinical case reports. For instance, Ly S et al. described a patient with pituitary adenoma suffered pituitary hemorrhage during treatment with Rivaroxaban \u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e. This emphasizes the necessity for heightened clinical vigilance and monitoring of such adverse reactions when administering NOACs.\u003c/p\u003e \u003cp\u003eWhen investigating the disparities in anticoagulant utilization between pediatric and adult populations, multiple critical factors warrant consideration. On the one hand, the hemostatic system in children evolves with age \u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e. There are significant differences in the plasma concentrations of hemostatic proteins that regulate thrombus formation and dissolution across different age groups, ranging from preterm infants to adults. For example, full-term neonates exhibit antithrombin levels that are only 50\u0026ndash;75% of those found in adults, with even lower levels observed in preterm infants. These concentrations generally approximate adult levels by the age of 6\u0026ndash;12 months \u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e. On the other hand, the pharmacokinetics (PK) and pharmacodynamics (PD) of anticoagulants are also age-dependent. Children have lower plasma proteins, increased apparent volume of distribution, increased clearance rates, and shorter half-lives, leading to PK and PD differences between children and adults, as well as dietary types can significantly influence drug absorption, particularly in neonates \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. Moreover, the difficulty of administration and the epidemiology of VTE also contribute to the differences in anticoagulant use between children and adults.\u003c/p\u003e \u003cp\u003eThere are several limitations to using the FAERS database for pharmacovigilance analysis. Primarily, while the frequency of reports can be estimated, the actual incidence of AE associated with NOACs cannot be determined through this spontaneous reporting system. Additionally, the sources of the reports in the FAERS database are heterogeneous. These reports frequently lack comprehensive clinical details constrains our capacity to thoroughly examine the AE signals related to NOACs. Nevertheless, the FAERS database continues to serve as one of the largest repositories of post-marketing drug event data globally, amassing millions of reports from both the United States and internationally. This extensive and varied dataset offers a crucial resource for investigating potential drug-AE associations, thereby playing a pivotal role in drug safety.\u003c/p\u003e"},{"header":"5 Conclusion","content":"\u003cp\u003eNOACs are widely used in the treatment of various thrombotic diseases, and associated with a spectrum of potential adverse reactions. This pharmacovigilance study provides valuable information on the use of NOACs in pediatric populations. It is crucial to closely monitor adverse events related to the Reproductive system and breast disorders, Renal and urinary disorders, Skin and subcutaneous tissue disorders, Investigations, Vascular disorders and Hepatobiliary disorders. Additionally, clinicians should be vigilant for unexpected and strongly signaled adverse events, such as Low birth weight baby, Suicide attempt, Intentional self-injury, Foetal exposure during pregnancy, and Alopecia found in pediatric population.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical considerations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThese data can be found at: https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html. Further inquiries can be directed to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGG: Data curation, Formal Analysis, Investigation, Writing\u0026ndash;original draft, Writing\u0026ndash;review and editing. TC: Formal Analysis, Visualization, Writing\u0026ndash;original draft, Writing\u0026ndash;review and editing. LY: Formal Analysis, Visualization, Writing\u0026ndash;review and editing. JZ: Formal Analysis, Writing\u0026ndash;review and editing. JZ: Conceptualization, Methodology, Writing\u0026ndash;review and editing.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Natural Science Foundation of Fujian Province (No.2022J011037)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank the FAERS database for freely providing the open-source data. They also thank the experts who provided valuable suggestions for the successful completion of this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePublisher\u003c/strong\u003e\u003cstrong\u003e\u0026rsquo;\u003c/strong\u003e\u003cstrong\u003es note\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eRaffini L, Huang YS, Witmer C, Feudtner C. Dramatic increase in venous thromboembolism in children\u0026apos;s hospitals in the United States from 2001 to 2007. Pediatrics 2009; 124(4):1001-1008. doi: 10.1542/peds.2009-0768\u003c/li\u003e\n\u003cli\u003eStein PD, Kayali F, Olson RE. Incidence of venous thromboembolism in infants and children: data from the National Hospital Discharge Survey. J Pediatr 2004; 145(4):563-565. doi: 10.1016/j.jpeds.2004.06.021\u003c/li\u003e\n\u003cli\u003eYee DL, O\u0026rsquo;Brien SH, Young G. Pharmacokinetics and Pharmacodynamics of Anticoagulants in Paediatric Patients. Clinical Pharmacokinetics 2013; 52(11):967-980. doi: 10.1007/s40262-013-0094-1\u003c/li\u003e\n\u003cli\u003eBadimon JJ, Escolar G, Zafar MU. Factor XI/XIa Inhibition: The Arsenal in Development for a New Therapeutic Target in Cardio- and Cerebrovascular Disease. J Cardiovasc Dev Dis 2022; 9(12). doi: 10.3390/jcdd9120437\u003c/li\u003e\n\u003cli\u003eAgeno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141(2 Suppl):e44S-e88S. doi: 10.1378/chest.11-2292\u003c/li\u003e\n\u003cli\u003eGarcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141(2 Suppl):e24S-e43S. doi: 10.1378/chest.11-2291\u003c/li\u003e\n\u003cli\u003eMikler J, Samos M, Bolek T, Skornova I, Stanciakova L, Stasko J, et al. Direct Oral Anticoagulants: Novel Approach for the Treatment of Thrombosis in Pediatric Patients? Pediatr Cardiol 2019; 40(7):1431-1438. doi: 10.1007/s00246-019-02159-3\u003c/li\u003e\n\u003cli\u003eYu X, Zhu W, Liu C, Lu R. Direct Oral Anticoagulants for Treating Acute Venous Thromboembolism in Children: Meta-Analysis of Randomized Controlled Trials. Clin Appl Thromb Hemost 2024; 30:10760296241271386. doi: 10.1177/10760296241271386\u003c/li\u003e\n\u003cli\u003eAlqahtani S, Gibbs KD, Montanez NA, Krause KJ, van Ommen CH, Srivaths LV. Direct oral anticoagulant therapy in adolescent venous thromboembolism: A systematic review. Pediatr Blood Cancer 2024; 71(9):e31131. doi: 10.1002/pbc.31131\u003c/li\u003e\n\u003cli\u003eCao Z, Fu Z, Liu Y, Liu T, Zhan M, Liu X, et al. Probable rivaroxaban-induced erythema multiforme in children: A case report. Saudi Pharm J 2023; 31(11):101801. doi: 10.1016/j.jsps.2023.101801\u003c/li\u003e\n\u003cli\u003eSpiezia L, Campello E, Tormene D, Simioni P. Venous Thromboembolism in Children: The Rivaroxaban Experience. Semin Thromb Hemost 2024; 50(6):866-872. doi: 10.1055/s-0043-1778106\u003c/li\u003e\n\u003cli\u003eBhat RV, Young G, Sharathkumar AA. How I treat pediatric venous thromboembolism in the DOAC era. Blood 2024; 143(5):389-403. doi: 10.1182/blood.2022018966\u003c/li\u003e\n\u003cli\u003evan Ommen CH, Albisetti M, Chan AK, Estepp J, Jaffray J, Kenet G, et al. The Edoxaban Hokusai VTE PEDIATRICS Study: An open-label, multicenter, randomized study of edoxaban for pediatric venous thromboembolic disease. Res Pract Thromb Haemost 2020; 4(5):886-892. doi: 10.1002/rth2.12352\u003c/li\u003e\n\u003cli\u003eFDA Approved Drug Products: Xarelto (rivaroxaban) tablets/suspension for oral administration (February 2023). https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022406s041lbl.pdf\u003c/li\u003e\n\u003cli\u003eGeorge C, Rahman M, Monagle P. Challenges and Opportunities in the Pharmacological Treatment of Acute Venous Thromboembolism in Children. Paediatr Drugs 2020; 22(4):385-397. doi: 10.1007/s40272-020-00403-5\u003c/li\u003e\n\u003cli\u003eDrugBank. \u0026lt;https://go.drugbank.com/\u0026gt;. \u003c/li\u003e\n\u003cli\u003eFDA\u0026rsquo;s Orange Book. \u0026lt;https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm\u0026gt;. \u003c/li\u003e\n\u003cli\u003eMedical Dictionary for Regulatory Activities. \u0026lt;https://www.meddra.org/how-to-use/support-documentation/chinese/welcome\u0026gt;. \u003c/li\u003e\n\u003cli\u003eInvestigators E, Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363(26):2499-2510. doi: 10.1056/NEJMoa1007903\u003c/li\u003e\n\u003cli\u003eMale C, Lensing AWA, Palumbo JS, Kumar R, Nurmeev I, Hege K, et al. Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial. Lancet Haematol 2020; 7(1):e18-e27. doi: 10.1016/S2352-3026(19)30219-4\u003c/li\u003e\n\u003cli\u003eJacobson-Kelly AE, Samuelson Bannow BT. Abnormal uterine bleeding in users of rivaroxaban and apixaban. Hematology Am Soc Hematol Educ Program 2020; 2020(1):538-541. doi: 10.1182/hematology.2020000166\u003c/li\u003e\n\u003cli\u003eMonagle P, Lensing AWA, Thelen K, Martinelli I, Male C, Santamaria A, et al. Bodyweight-adjusted rivaroxaban for children with venous thromboembolism (EINSTEIN-Jr): results from three multicentre, single-arm, phase 2 studies. Lancet Haematol 2019; 6(10):e500-e509. doi: 10.1016/S2352-3026(19)30161-9\u003c/li\u003e\n\u003cli\u003eQian Y, Zhao X, Liu D, Liu J, Yue Z, Liu W. Adverse events of direct factor Xa inhibitors: a disproportionality analysis of the FAERS database. Expert Opin Drug Saf 2024:1-10. doi: 10.1080/14740338.2024.2368815\u003c/li\u003e\n\u003cli\u003eAlshammari TM, Ata SI, Mahmoud MA, Alhawassi TM, Aljadhey HS. Signals of bleeding among direct-acting oral anticoagulant users compared to those among warfarin users: analyses of the post-marketing FDA Adverse Event Reporting System (FAERS) database, 2010-2015. Ther Clin Risk Manag 2018; 14:803-809. doi: 10.2147/TCRM.S161148\u003c/li\u003e\n\u003cli\u003eNathan KT, Conn KM, van Manen RP, Brown JE. Signal detection for bleeding associated with the use of direct oral anticoagulants. Am J Health Syst Pharm 2018; 75(13):973-977. doi: 10.2146/ajhp170529\u003c/li\u003e\n\u003cli\u003eRaschi E, Poluzzi E, Koci A, Salvo F, Pariente A, Biselli M, et al. Liver injury with novel oral anticoagulants: assessing post-marketing reports in the US Food and Drug Administration adverse event reporting system. Br J Clin Pharmacol 2015; 80(2):285-293. doi: 10.1111/bcp.12611\u003c/li\u003e\n\u003cli\u003eCicione A, Lombardo R, Gallo G, Guidotti A, Zammitti F, Ghezzo N, et al. Medications mostly associated with hematuria: assessment of the EudraVigilance and Food and Drug Administration pharmacovigilance databases entries. Minerva Urol Nephrol 2024; 76(1):68-73. doi: 10.23736/S2724-6051.22.05018-2\u003c/li\u003e\n\u003cli\u003eWu J, Wu J, Tang B, Wang X, Wei F, Zhang Y, et al. Suspected adverse drug reactions of rivaroxaban reported in the United States food and drug administration adverse event reporting system database: a pharmacovigilance study. Front Pharmacol 2024; 15:1399172. doi: 10.3389/fphar.2024.1399172\u003c/li\u003e\n\u003cli\u003eLy S, Naman A, Chaufour-Higel B, Patey M, Arndt C, Delemer B, et al. Pituitary apoplexy and rivaroxaban. Pituitary 2017; 20(6):709-710. doi: 10.1007/s11102-017-0828-4\u003c/li\u003e\n\u003cli\u003eAndrew M. Developmental hemostasis: relevance to thromboembolic complications in pediatric patients. Thromb Haemost 1995; 74(1):415-425. doi: \u003c/li\u003e\n\u003cli\u003eYee DL, O\u0026apos;Brien SH, Young G. Pharmacokinetics and pharmacodynamics of anticoagulants in paediatric patients. Clin Pharmacokinet 2013; 52(11):967-980. doi: 10.1007/s40262-013-0094-1\u003c/li\u003e\n\u003cli\u003eMonagle P, Barnes C, Ignjatovic V, Furmedge J, Newall F, Chan A, et al. Developmental haemostasis. Impact for clinical haemostasis laboratories. Thromb Haemost 2006; 95(2):362-372. doi: 10.1160/TH05-01-0047\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"novel oral anticoagulants, pediatric, disproportionate analysis, adverse events, FAERS database","lastPublishedDoi":"10.21203/rs.3.rs-5713066/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5713066/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e This study utilizes the FDA Adverse Event Reporting System (FAERS) database to analyze and compare the actual adverse event (AE) signals of novel oral anticoagulants (NOACs) in the overall population and pediatric patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eThis study conducted a comprehensive disproportionate analysis to assess the correlation between NOACs and AEs, covering from the third quarter of 2014 to the first quarter of 2024 in the overall and pediatric population. This analysis utilized statistical methodologies including the ROR, PRR, BCPNN, and EBGM to elucidate potential signals of drug-related AEs.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eIn the pediatric population, there were 820 AE reports related to NOACs. Injury, poisoning and procedural complications (20.98%), Vascular disorders (8.90%), and Respiratory, thoracic and mediastinal Disorders (3.41%) are significant SOC categories of AEs, and PTs show high signal strength such as Haemorrhoidal haemorrhage (n=3, ROR [95% CI]: 1008.19[240.54;4225.69], PRR [95% CI]: 1004.51[240.45;4196.45], IC [IC025]: 2.81[0.74], EBGM [EBGM05]: 628.19[1.54]), Pelvic venous thrombosis (n=3, ROR [95% CI]: 240.04[71.46;806.33], PRR [95% CI]: 239.17[71.48;800.28], IC [IC025]: 2.81[0.74], EBGM [EBGM05]:209.4[1.59]), and Thrombophlebitis (n=3, ROR [95% CI]: 129.25[39.86;419.09], PRR [95% CI]: 128.78[39.88;415.9], IC [IC025]: 2.8[0.74], EBGM [EBGM05]: 119.66[1.48]). Additionally, clinicians should be vigilant for unexpected and strongly signaled adverse events, like Low birth weight baby, Suicide attempt, Intentional self-injury, Foetal exposure during pregnancy, and Alopecia .\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThis pharmacovigilance study provides valuable information on the use of NOACs in pediatric populations. It is crucial to closely monitor adverse events related to multiple systems and organs. However, the disproportionality analysis is hypothesis generating , causality and risk levels of adverse effects cannot be accurately inferred.\u003c/p\u003e","manuscriptTitle":"A disproportionate analysis of novel oral anticoagulants in the overall and pediatric populations: a pharmacovigilance study based on FDA Adverse Event Reporting System database","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-01 09:16:12","doi":"10.21203/rs.3.rs-5713066/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"51f34c16-8218-4b6e-a9d3-b2e8e6c399e5","owner":[],"postedDate":"January 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-05T10:41:09+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-01 09:16:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5713066","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5713066","identity":"rs-5713066","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}