Comparison of Efficacy of Nadroparin and Fondaparinux sodium for Prevention of Deep Vein Thromboembolism in lower extremities after Total Hip Arthroplasty and Total Knee Arthroplasty: a retrospective study of 592 patients

Comparison of Efficacy of Nadroparin and Fondaparinux sodium for Prevention of Deep Vein Thromboembolism in lower extremities after Total Hip Arthroplasty and Total Knee Arthroplasty: a retrospective study of 592 patients | 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 Comparison of Efficacy of Nadroparin and Fondaparinux sodium for Prevention of Deep Vein Thromboembolism in lower extremities after Total Hip Arthroplasty and Total Knee Arthroplasty: a retrospective study of 592 patients Xiang Gao, Xiaowei Jin, Rui Huang, Zhenxing Li, Hanle Zhang, Pei Fan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3825170/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 14 You are reading this latest preprint version Abstract Objectives: To compare the efficacy of nadroparin and fondaparinux sodium for prevention of deep vein thromboembolism (DVT) in lower extremities after total hip arthroplasty (THA) and total knee arthroplasty (TKA). Methods： A total of 592 patients were enrolled in the study. Clinical data of patients who underwent total hip arthroplasty (THA) and total knee arthroplasty (TKA) in our hospital from December 2021 to September 2022 were retrospectively collected, which mainly included patients' general information, surgery-related information, and DVT-related information. The patients were categorized into the nadroparin group(n=278) and the fondaparinux sodium group(n=314) according to the types of anticoagulants used. Anticoagulant therapy began 12-24 hours after operation and continued until discharge. DVT prevalence between two groups was compared. The Statistical Package for Social Sciences (SPSS) software version 25 (SPSS, Armonk, NY, USA) was used for statistical analysis. Results： The prevalence of DVT in the nadroparin group and the fondaparinux sodium group was 8.3% (23/278) and 15.0% (47/314), respectively(p=0.012). Statistical analysis showed that nadroparin group showed a lower prevalence of thrombosis than fondaparinux group (OR=1.952, P=0.012). Subgroup analyses showed that nadroparin group had a lower prevalence of DVT than fondaparinux group in some special patients groups such as female patients (OR=2.258, P= 0.007), patients who are 65-79 years old (OR=2.796, P = 0.004), patients with hypertension (OR=2.237, P=0.042), patients who underwent TKA (OR = 2.091, P=0.011), and patients who underwent combined spinal-epidural anesthesia (OR=2.490, P=0.003) (P<0.05). Conclusion: Nadroparinmay have an advantage over fondaparinux sodium in preventing DVT in lower extremities after THA and TKA. Deep Vein Thromboembolism Nadroparin Fondaparinux Sodium Total Hip Arthroplasty Total Knee Arthroplasty Figures Figure 1 Figure 2 Introduction Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), is a serious complication with high prevalence during hospitalization and perioperative period, affecting nearly 10 million people worldwide each year[ 1 – 3 ]. VTE is a multifactorial disease caused by the interaction of multiple predisposing factors, which can be transient or persistent, and strong transient predisposing risk factors such as major surgery, prolonged immobilization, and major trauma, accounting for approximately 20% of all VTE events[ 4 ]. In the absence of thromboprophylaxis, the prevalence of DVT after orthopedic surgery varies from 42–57% after THA and from 41–85% after TKA[ 5 ], and is as high as 60% after lower extremities orthopedic surgery within 2 weeks, of which 14% develop symptoms[ 6 ]. Compared with non-surgical patients, THA or TKA patients had the highest risk of VTE [odds ratio (OR) > 10][ 7 ]. In addition, patients undergoing THA or TKA have a higher risk of VTE due to concurrent risk factors, such as age > 60 years, obesity [body mass index (BMI) > 30], diabetes, dyslipidemia and inflammatory diseases, and all the above are common risk factors for VTE and osteoarthritis[ 8 ]. Although VTE is a serious complication during hospitalization and perioperative period, it is preventable[ 6 ]. Effective anticoagulation prophylaxis for patients undergoing major orthopedic surgery can not only reduce the prevalence and mortality of VTE, but also alleviate pain for patients and reduce medical expenses[ 5 , 9 ]. Current preventive measures include primary prevention, physical prevention, and pharmacological prevention, and pharmacological prevention is considered one of the most effective ways to reduce the risk of DVT in lower extremities[ 10 ]. Commonly used anticoagulants in hospital include unfractionated heparin (UFH), low-molecular-weight heparins (LMWHs), fondaparinux sodium and danaparoid[ 11 ]. Among them, LMWHs mainly include enoxaparin (low-molecular-weight heparin sodium) and nadroparin (low-molecular-weight heparin calcium)[ 11 ]. Nadroparin and fondaparinux sodium are two commonly used anticoagulants in clinical practice. However, the efficacy between nadroparin and fondaparinux sodium for prevention of DVT in lower extremities is still unclear. Previous studies have found fondaparinux sodium to be superior to enoxaparin in preventing VTE[ 12 , 13 ]. Related studies in China have shown that fondaparinux sodium is superior to LMWHs in preventing DVT in patients undergoing major orthopedic surgery[ 14 ], but this study does not limit the types of LMWHs. Some investigators have studied the prevention of thrombosis after minimally invasive esophagectomy(MIE) with nadroparin and fondaparinux sodium, and found that the prevalence rate of fondaparinux sodium was lower than that of nadroparin, so the investigators believe that fondaparinux sodium had similar efficacy in the prevention of thrombosis after MIE compared with nadroparin[ 15 ], but the sample size was small (N = 116). Therefore, we were curious about the performance of nadroparin and fondaparinux sodium in preventing DVT in lower extremities after joint arthroplasty. The aim of this study was to retrospectively study the data of patients undergoing THA and TKA in the Second Affiliated Hospital of Wenzhou Medical University, in order to compare the prevalence of VTE with nadroparin and fondaparinux sodium for the prevention of VTE after THA and TKA. Materials and Methods Study Population This study retrospectively analyzed 572 patients who underwent THA and TKA in the Department of Orthopedics of the Second Affiliated Hospital of Wenzhou Medical University from December 2021 to August 2022. Inclusion and Exclusion Criteria The inclusion criteria in our study were: (i) patients who were admitted to our hospital from December 2021 to August 2022; (ii) patients who underwent THA or TKA during hospitalization; (iii) ultrasonography of lower extremity veins was performed before and after operation; (iv) no deep venous thrombosis occurred before operation; (v) nadroparin and fondaparinux sodium was used for postoperative prophylaxis; (vi) patients agree to receive anticoagulant therapy to prevent thrombosis and submit signed informed consent. The exclusion criteria were as follows: (i) deep vein thrombosis had occurred before operation; (ii) no ultrasonic examination of lower extremity vein was performed during hospitalization; (iii) anticoagulants other than nadroparin and fondaparinux sodium were used; (iv) patients refused to accept anticoagulant therapy; (v) patients with contraindications for anticoagulation, such as patients with a history of allergy to anticoagulants, acute bacterial endocarditis, thrombocytopenia, fresh bleeding, stroke within 3 months. We reviewed a total of 676 patients who underwent THA and TKA in the Department of Orthopedics of the Second Affiliated Hospital of Wenzhou Medical University from December 2021 to August 2022. According to the inclusion criteria and exclusion criteria, 104 patients were excluded, and a total of 572 patients were finally included in this study. Data Collection Administration of Anticoagulants All admitted patients routinely assessed thromboembolic risk using a scoring scale. We also assessed patients for contraindications to anticoagulation. For patients with no contraindication to anticoagulation, Nadroparin (Fraxiparine, GlaxoSmithKline, UK) or Fondaparinux Sodium (Hengrui, Jiangsu, China) was administered subcutaneously on the first postoperative day to prevent DVT. Anticoagulant therapy began 12–24 hours after operation and continued until discharge. In details, the nadroparin was applied as follows: 0.4 mL (4100AxaIU) per day, subcutaneous injection for 14 days beginning 24 h after discontinuation of anesthesia; The fondaparinux sodium was applied as follows: 0.25 mg per day, subcutaneous injection for 14 days beginning 24 h after discontinuation of anesthesia. Diagnosis of DVT DVT was diagnosed according to the criteria of Fraser et al.[ 16 ]. Doppler ultrasound was used to diagnose DVT. The patients were examined on the second day preoperatively and postoperatively. General Characteristics We collected general information (gender, age, body mass index, etc.), current medical history, past medical history (diabetes, hypertension, coronary heart disease), postoperative Caprini score, drug precautions, surgery-related information (surgical methods, anesthesia methods, etc.), thrombosis prevalence (whether thrombosis occurred). The outcome variable was the occurrence of nosocomial thrombosis. Statistical Analysis The Statistical Package for Social Sciences (SPSS) software version 25 (SPSS, Armonk, NY, USA) was used for statistical analysis. The Shapiro-Wilks test was used to assess the distribution of the data. Continuous variables were expressed as mean ± standard deviation. Student's t-test was used for parametric analysis of continuous variables and Mann-Whitney U test was used for nonparametric analysis of continuous variables. Chi-square test or Fisher's exact test was used for categorical variables analysis. P < 0.05 was considered significant. Results Patients demography After applying the inclusion and exclusion criteria, a total of 592 THA or TKA patients admitted to our hospital between December 1, 2021 and August 31, 2022 were included. 278 patients received nadroparin and 314 patients received fondaparinux sodium. The demographic data and baseline levels were recorded. The mean age was 68.85 ± 10.007 years in nadroparin group while 67.06 ± 10.688 years in fondaparinux sodium group. The proportion of males was 37.1% in nadroparin group while 29.9% in fondaparinux sodium group. In addition, we divided all patients into 3 age groups to balance baseline data for age. The detailed information about other clinical characteristics, including comorbidity, type of surgery and type of anesthesia between the two groups is exhibited in Table 1 . Statistical analysis showed that baseline data were balanced and comparable between the two groups. Table 1 Patients demography Nadroparin (n = 278) no. (%) Fondaparinux Sodium (n = 314) no. (%) P-value DVT 23(8.3) 47(15.0) Gender 0.067 Female-no.(%) 175(62.9) 220(70.1) Male-no.(%) 103(37.1) 94(29.9) Age (mean ± SD) 68.85 ± 10.007 67.06 ± 10.688 Age stratification ≥ 80 year.-no. (%) 35(12.6) 25(8.0) 0.573 65–79 year.-no. (%) 160(57.6) 187(59.6) 0.325 ༜65 year.-no. (%) 83(29.8) 102(32.4) 0.155 Comorbidity Hypertension - no. (%) 131(47.1) 141(44.9) 0.589 Type 2 diabetes - no. (%) 45(16.2) 45(14.3) 0.530 Coronary heart disease - no. (%) 9(3.2) 2(0.6) 0.019 Type of surgery 0.051 THA- no. (%) 108(38.8) 98(31.2) TKA- no. (%) 170(61.2) 216(68.8) Type of anesthesia 0.243 General anesthesia- no. (%) 96(34.5) 123(39.2) Combined spinal-epidural anesthesia- no. (%) 182(65.5) 191(60.8) DVT prevalence A total of 592 patients were included in the study. Among all patients, 70 patients had thrombosis and 522 patients had no thrombosis, and the prevalence of thrombosis was 11.8%. In patients treated with nadroparin, 23 patients experienced thrombosis and 255 patients did not, resulting in a thrombosis rate of 8.3%. Among patients receiving fondaparinux sodium, 47 patients developed thrombosis and 267 patients did not develop thrombosis, with a thrombosis prevalence of 15.0%. Comparing the two anticoagulants, nadroparin showed a lower prevalence of DVT than fondaparinux sodium (8.3% vs. 15.0%, OR = 1.952, 95% CI = 1.152–3.307, P = 0.012). The DVT prevalence is illustrated in Table 2 and its OR and 95%CI is illustrated in Fig. 1 . Among all patients with DVT, 67 patients developed intermuscular venous plexus thrombosis, 1 patient developed anterior tibial vein thrombosis, 1 patient developed posterior tibial vein thrombosis, and 1 patient developed both anterior tibial and posterior tibial thrombosis. The proportion of the 4 types of thrombosis is illustrated in Fig. 2 . Table 2 DVT prevalence Nadroparin (n = 278) no. (%) Fondaparinux Sodium (n = 314) no. (%) P-value OR (95% CI) DVT 23/278(8.3%) 47/314(15.0) 0.012 1.952 (1.152–3.307) Subgroup Analysis Statistical analysis of subgroups showed that nadroparin showed a lower prevalence of DVT than fondaparinux sodium in some special patients groups such as female patients (OR = 2.258, 95%CI = 1.238–4.119, P = 0.007), patients who are 65–79 years old (OR = 2.796, 95%CI = 1.360–5.751, P = 0.004), patients with hypertension (OR = 2.237, 95%CI = 1.016–4.925, P = 0.042), patients who underwent TKA (OR = 2.091, 95%CI = 1.172–3.732, P = 0.011), and patients who underwent combined spinal-epidural anesthesia (OR = 2.490, 95%CI = 1.352–4.587, P = 0.003). In other patients groups such as male patients, patients with diabetes mellitus, patients with coronary heart disease, patients who underwent THA, patients who underwent general anesthesia, there was no statistical significance between two drugs in the prevention of VTE. All statistics is illustrated in Table 3 and Fig. 1 . Table 3 Subgroup Analysis of DVT in hospital Outcome Nadroparin (n = 278) no. (%) Fondaparinux Sodium (n = 314) no. (%) P-value OR (95%CI) Gender Female-no.(%) 17/175(9.7) 43/220(19.5) 0.007 2.258(1.238–4.119) Male-no.(%) 6/103(5.8) 4/94(4.3) 0.860 - Age stratification ≥ 80 year.-no. (%) 4/35(11.4) 5/25(20.0) 0.582 - 65–79 year.-no. (%) 11/160(6.9) 32/187(17.1) 0.004 2.796(1.360–5.751) ༜65 year.-no. (%) 8/83(9.6) 10/102(9.8) 0.970 - Comorbidity Hypertension - no. (%) 10/131(7.6) 22/141(15.6) 0.042 2.237(1.016–4.925) Type 2 diabetes - no. (%) 2/45(4.4) 7/45(15.6) 0.16 - Coronary heart disease - no. (%) 1/9(11.1) 0/2(0) - - Type of surgery THA- no. (%) 1/108(0.9) 2/98(2.0) 0.932 - TKA- no. (%) 19/170(11.2) 45/216(20.8) 0.011 2.091(1.172–3.732) Type of anesthesia General anesthesia- no. (%) 6/96(6.3) 8/123(6.5) 0.939 - Combined spinal-epidural anesthesia- no. (%) 17/182(9.3) 39/191(20.4) 0.003 2.490(1.352–4.587) VTE prevalence in different type of surgery using the same anticoagulants Moreover, we also compared whether there was any difference in the prevalence of DVT after THA and TKA among patients using the same anticoagulants. The results showed that among patients using nadroparin, 3.7% of THA and 11.2% of TKA patients developed DVT. Meanwhile, among patients using fondaparinux, DVT occurred in 2.0% of THA patients and 20.8% of TKA patients. Statistical analysis showed there was statistical significance between the prevalence of DVT of two types of surgery, no matter using which anticoagulants. The statistics is illustrated in Table 4 and Fig. 1 . Table 4 VTE prevalence in different type of surgery using the same anticoagulants Type of surgery DVT P-value OR (95% CI) Nadroparin THA- no. (%) 4(3.7) 0.027 3.272 (1.082–9.895) TKA- no. (%) 19(11.2) Fondaparinux sodium THA- no. (%) 2(2.0) ༜0.001 12.632 (2.998–53.221) TKA- no. (%) 45(20.8) Discussion DVT is common after major surgery or severe trauma, long-term bedridden, limb immobilization and so on[ 17 ]. Previous study suggests that the prevalence of DVT after orthopedic surgery varies from 42–57% after THA and from 41–85% after TKA without thromboprophylaxis[ 5 ]. In our study, the prevalence of thrombosis was 11.8% with thromboprophylaxis. Although no study has been reported on nadroparin and fondaparinux sodium for the prevention of lower extremity DVT after orthopedic joint replacement surgery, previously. Nevertheless, our results show that the administration of 4100AxaIU nadroparin significantly reduced the prevalence of postoperative DVT compared with the administration of 2.5 mg fondaparinux in patients undergoing THA and TKA. A number of randomized controlled clinical trials have shown fondaparinux sodium to be superior to enoxaparin in the prevention of VTE following hip fracture, hip replacement, and major knee surgery[ 12 , 13 , 18 ]. A real-world study conducted in China retrospectively analyzed the prevention of VTE in patients undergoing major orthopedic surgery and trauma, suggesting that fondaparinux sodium may show better thromboprophylaxis effect in hospitalized patients undergoing major orthopedic surgery or trauma than LMWHs, especially in some special patient populations such as elderly patients, patients with renal impairment, patients with hypertension, etc.[ 14 ]. However, the LMWHs used in this study did not limit the types of anticoagulants (nadroparin or fondaparinux sodium), which may affect the accuracy of the results. Currently, there still lack studies that systematically review the efficacy and safety of enoxaparin and nadroparin in the prevention of VTE after major orthopedic surgery. The American College of Chest Physicians (ACCP) guidelines recommend the use of LMWH, low-dose unfractionated heparin (UFH), vitamin K antagonist (VKA), fondaparinux, apixaban, dabigatran, rivaroxaban, or aspirin for patients who undergo TKA or THA to prevent VTE[ 19 ]. LMWHs are derived from UFH by chemical or enzymatic depolymerization. Enoxaparin is derived from UFH by benzylation followed by alkaline depolymerization, has an average molecular weight of 3500-5500Da, and contains 10000 International Unit (IU) of anti-Xa factor (AxaIU, WHO compendial units) per ml[ 11 ]. Nadroparin is derived from UFH by nitrous acid depolymerization, has an average molecular weight of 3600-5000Da, and contains 10250 AxaIU per ml[ 11 ]. LMWHs exert their primary anticoagulant effect by catalyzing AT-mediated inhibition of coagulation factors. The thromboprophylaxis efficacy of LMWHs is equivalent to that of low-dose subcutaneous UFH, with a lower risk of bleeding complications and fewer heparin-related side effects[ 20 ]. Fondaparinux sodium is an artificially isolated natural high-affinity pentasaccharide, synthesized after modification, with a molecular weight of 1728Da[ 11 ]. UFH and LMWHs bind to antithrombin III (AT III) and enhance its affinity for thrombin and factor Xa, whereas fondaparinux only enhances the affinity of AT III and factor Xa[ 11 ]. Although fondaparinux sodium has been reported to have higher specific anti-Xa activity than LMWHs (approximately 700 units/mg and 100 units/mg, respectively) and a longer half-life after subcutaneous injection than LMWHs (approximately 17h and 4h, respectively), Garcia et al. considered that the validity of low molecular weight heparin as a reference preparation to determine fondaparinux sodium anti-Xa activity is doubtful[ 11 ]. The ACCP recommends LMWHs as optimal pharmacological agents for VTE prophylaxis in patients undergoing THA, TKA, or hip fracture surgery[ 21 ]. According to Yngve et al., based on moderate-quality evidence, the use of fondaparinux sodium compared with LMWHs does not appear to reduce patient-important VTE events but may increase major bleeding events by nine per 1,000[ 21 ]. Besides, The ACCP advised to use fondaparinux sodium cautiously in patients weighing less than 50 kg and elderly and frail patients because bleeding complications may be increased[ 21 ]. Subgroup analyses identified a lower prevalence of DVT in the nadroparin group than that in the fondaparinux sodium group in some special patients groups, including female patients, patients who are 65–79 years old, patients with hypertension, patients who underwent TKA, and patients who underwent combined spinal-epidural anesthesia. This may provide an idea for individualized and precise prevention of DVT after THA and TKA. Our results showed that TKA was associated with a higher prevalence of DVT than THA, which is consistent with the results of Senay et al[ 22 ]. In their study, the DVT prevalence rates was 2.2% after TKA and 0.4% after THA during hospitalization. Bedsides, a meta-analysis of 47 studies performed by Januel et al reported that the pooled prevalence rates of VTE for patients treated with LMWHs were 1.4% (95% CI: 1.0–1.8%) in TKA studies and 0.6% (95% CI: 0.4–0.8%) in THA studies[ 23 ]. The above studies collected symptomatic VTE, whereas we routinely screened and included many asymptomatic patients with thrombosis, so the prevalence of VTE in our study was higher than the above studies. At the same time, our study found that the prevalence of lower limb intermuscular venous plexus thrombosis was very high, and most of them were asymptomatic. Therefore, attention should be paid to the screening and prevention of lower limb intermuscular venous plexus thrombosis. The Limitations of This Study Our study has several limitations and shortcomings. Firstly, it was a single-center retrospective study and selection bias was unavoidable. Secondly, the sample size included in the study was limited, but it is quite enough for the study. Finally, there is a lack of comparison of the efficacy of different types of LMWHs. Conclusion In conclusion, the use of 4100AxaIU nadroparin may demonstrate better prevention of DVT in the lower extremities after THA and TKA than 2.5 mg fondaparinux sodium, especially in certain populations such as female patients, patients aged 65–79 years, patients with hypertension, patients underwent TKA, and patients underwent combined spinal-epidural anesthesia. We call for multicenter, large-sample clinical investigations or randomized controlled trials to further elucidate the preventive effects of different anticoagulants on DVT in the lower extremities. Declarations Ethical Approval The protocol of this retrospective study was approved by the ethics committees of the Second Affiliated Hospital of Wenzhou Medical University. Consent to Participate Informed consent was obtained from all patients. Consent to Publish Not applicable Author contributions Study conception and design: XG and PF. Collection and assembly of data: XG, XWJ, RH, ZXL, HLZ and PF. SPSS statistical analysis: XG and PF. Analysis and interpretation of data: XG and PF. Manuscript: XG and PF. All authors reviewed the manuscript and approved the final version to be published. Funding Not applicable. Competing Interests The authors declare that they have no competing interests Availability of data and materials The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. Acknowledgments Not applicable. References Khan F, Tritschler T, Kahn SR, Rodger MA. Venous thromboembolism. Lancet. 2021;398:64–77. Chinese Orthopaedic Association. Prevention of venous thromboembolism after major orthopaedic surgery. Orthop Surg. 2010;2:81–5. Yu HT, Dylan ML, Lin J, Dubois RW. Hospitals' compliance with prophylaxis guidelines for venous thromboembolism. Am J Health Syst Pharm. 2007;64:69–76. Heit JA. Epidemiology of venous thromboembolism. Nat Rev Cardiol. 2015;12:464–74. Streiff MB, Haut ER. The CMS ruling on venous thromboembolism after total knee or hip arthroplasty: weighing risks and benefits. JAMA. 2009;301:1063–5. Flevas DA, Megaloikonomos PD, Dimopoulos L, Mitsiokapa E, Koulouvaris P, Mavrogenis AF. Thromboembolism prophylaxis in orthopaedics: an update. EFORT Open Rev. 2018;3:136–48. Fisher WD. Impact of venous thromboembolism on clinical management and therapy after hip and knee arthroplasty. Can J Surg. 2011;54:344–51. van Oosterom N, Barras M, Bird R, Nusem I, Cottrell N. A Narrative Review of Aspirin Resistance in VTE Prophylaxis for Orthopaedic Surgery. Drugs. 2020;80:1889–99. Thirugnanam S, Pinto R, Cook DJ, Geerts WH, Fowler RA. Economic analyses of venous thromboembolism prevention strategies in hospitalized patients: a systematic review. Crit Care. 2012;16:R43. Di Nisio M, van Es N, Büller HR. Deep vein thrombosis and pulmonary embolism. Lancet. 2016;388:3060–73. 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:e24S–e43S. Bauer KA, Eriksson BI, Lassen MR, Turpie AG. Steering Committee of the Pentasaccharide in Major Knee Surgery Study. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery. N Engl J Med. 2001;345:1305–10. Lassen MR, Bauer KA, Eriksson BI, Turpie AG, European Pentasaccharide Elective Surgery Study (EPHESUS) Steering Committee. Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: a randomised double-blind comparison. Lancet. 2002;359:1715–20. Fu D, Li L, Li Y, Liu X, Chen H, Wu N, et al. Fondaparinux sodium and low molecular weight heparin for venous thromboembolism prophylaxis in Chinese patients with major orthopedic surgery or trauma: a real-world study. BMC Surg. 2022;22:243. Song J, Xuan L, Wu W, Shen Y, Tan L, Zhong M. Fondaparinux versus nadroparin for thromboprophylaxis following minimally invasive esophagectomy: A randomized controlled trial. Thromb Res. 2018;166:22–7. Fraser JD, Anderson DR. Venous protocols, techniques, and interpretations of the upper and lower extremities. Radiol Clin North Am. 2004;42:279–96. Righini M, Le Gal G, Bounameaux H. Venous thromboembolism diagnosis: unresolved issues. Thromb Haemost. 2015;113:1184–92. Eriksson BI, Bauer KA, Lassen MR, Turpie AG. Steering Committee of the Pentasaccharide in Hip-Fracture Surgery Study. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery. N Engl J Med. 2001;345:1298–304. Thiengwittayaporn S, Budhiparama N, Tanavalee C, Tantavisut S, Sorial RM, Li C, et al. Asia-Pacific venous thromboembolism consensus in knee and hip arthroplasty and hip fracture surgery: Part 3. Pharmacological venous thromboembolism prophylaxis. Knee Surg Relat Res. 2021;33:24. Bergqvist D. Low-molecular-weight heparin for the prevention of postoperative venous thromboembolism after abdominal surgery: a review. Curr Opin Pulm Med. 2005;11:392–7. Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S, et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e278S–e325S. Senay A, Trottier M, Delisle J, Banica A, Benoit B, Laflamme GY, et al. Incidence of symptomatic venous thromboembolism in 2372 knee and hip replacement patients after discharge: data from a thromboprophylaxis registry in Montreal, Canada. Vasc Health Risk Manag. 2018;14:81–9. Januel JM, Chen G, Ruffieux C, Quan H, Douketis JD, Crowther MA, et al. Symptomatic in-hospital deep vein thrombosis and pulmonary embolism following hip and knee arthroplasty among patients receiving recommended prophylaxis: a systematic review. JAMA. 2012;307:294–303. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 17 Apr, 2024 Reviews received at journal 08 Apr, 2024 Reviewers agreed at journal 17 Mar, 2024 Reviewers agreed at journal 22 Feb, 2024 Reviews received at journal 15 Feb, 2024 Reviewers agreed at journal 07 Feb, 2024 Reviews received at journal 16 Jan, 2024 Reviewers agreed at journal 02 Jan, 2024 Reviewers agreed at journal 01 Jan, 2024 Reviewers invited by journal 01 Jan, 2024 Editor assigned by journal 01 Jan, 2024 Editor invited by journal 31 Dec, 2023 Submission checks completed at journal 31 Dec, 2023 First submitted to journal 30 Dec, 2023 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-3825170","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":264776291,"identity":"07fa1584-d0fe-4029-82aa-23968af2f680","order_by":0,"name":"Xiang Gao","email":"","orcid":"","institution":"Second Affiliated Hospital \u0026 Yuying Children's Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xiang","middleName":"","lastName":"Gao","suffix":""},{"id":264776292,"identity":"9293e5d1-0bfd-4fc3-b67d-78772a0275ea","order_by":1,"name":"Xiaowei Jin","email":"","orcid":"","institution":"Second Affiliated Hospital \u0026 Yuying Children's Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xiaowei","middleName":"","lastName":"Jin","suffix":""},{"id":264776293,"identity":"01b7ce42-fdbe-4139-ad16-71206c4bdab1","order_by":2,"name":"Rui Huang","email":"","orcid":"","institution":"Second Affiliated Hospital \u0026 Yuying Children's Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Rui","middleName":"","lastName":"Huang","suffix":""},{"id":264776294,"identity":"26237f82-fd4e-4410-b142-d80f501bd311","order_by":3,"name":"Zhenxing Li","email":"","orcid":"","institution":"Second Affiliated Hospital \u0026 Yuying Children's Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhenxing","middleName":"","lastName":"Li","suffix":""},{"id":264776295,"identity":"da3afbc3-1691-41ad-9351-3e6c0102f71f","order_by":4,"name":"Hanle Zhang","email":"","orcid":"","institution":"Second Affiliated Hospital \u0026 Yuying Children's Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hanle","middleName":"","lastName":"Zhang","suffix":""},{"id":264776296,"identity":"f7f22bc3-3227-436d-91e9-5b40f1f1f460","order_by":5,"name":"Pei Fan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAv0lEQVRIiWNgGAWjYBAC9gYQaWAD4fEQo4XnAFhLGslaGA6TooX97LEHHwrOJ66dkcD44G0bg7w5QS08eemGMwxuJ267kcBsOLeNwXBnAwEt9gw5ZtI8BrdzgVrYpHnbGBIMDhCyhf+NmfQfg3MgLey/idMiAbSFweAA2BZmIrW8MTfsMUiu33bmYbPknHMShhsIOyzH7MGPP3bGZseTD354U2YjT9AWIGCD0owNQEKCsHokLaNgFIyCUTAKcAAAs1k9+KbE+xEAAAAASUVORK5CYII=","orcid":"","institution":"Second Affiliated Hospital \u0026 Yuying Children's Hospital of Wenzhou Medical University","correspondingAuthor":true,"prefix":"","firstName":"Pei","middleName":"","lastName":"Fan","suffix":""}],"badges":[],"createdAt":"2023-12-31 04:59:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3825170/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3825170/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49129964,"identity":"ea43addb-0836-4140-9c4c-ff0b8050bfd0","added_by":"auto","created_at":"2024-01-03 15:22:37","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":107377,"visible":true,"origin":"","legend":"\u003cp\u003eA.Nadroparin showed a lower prevalence of DVT than fondaparinux sodium.\u003c/p\u003e\n\u003cp\u003eB.Subgroup Analysis of DVT prevalence.\u003c/p\u003e\n\u003cp\u003eC.Prevalence of DVT after THA and TKA among patients using the same anticoagulants.\u003c/p\u003e\n\u003cp\u003eAbbreviation: CI, confidence interval; DVT, deep vein thrombosis;THA, total hip arthroplasty ; TKA, total knee arthroplasty.\u003c/p\u003e","description":"","filename":"OnlineFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-3825170/v1/61fb30db3aaaafdd155b649b.png"},{"id":49129353,"identity":"2621041f-1c7a-4f2e-83dd-e6cb258f79e3","added_by":"auto","created_at":"2024-01-03 15:14:37","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":122623,"visible":true,"origin":"","legend":"\u003cp\u003eThe proportion of the 4 types of thrombosis.\u003c/p\u003e","description":"","filename":"OnlineFigure2.png","url":"https://assets-eu.researchsquare.com/files/rs-3825170/v1/7d1c0fde17a4f3edeb50e830.png"},{"id":49130187,"identity":"1e5f90b3-de64-4cbb-ab55-b2625c8672b6","added_by":"auto","created_at":"2024-01-03 15:30:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":714056,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3825170/v1/ac606e8e-0fa0-442a-9a88-936322a93775.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparison of Efficacy of Nadroparin and Fondaparinux sodium for Prevention of Deep Vein Thromboembolism in lower extremities after Total Hip Arthroplasty and Total Knee Arthroplasty: a retrospective study of 592 patients","fulltext":[{"header":"Introduction","content":"\u003cp\u003eVenous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), is a serious complication with high prevalence during hospitalization and perioperative period, affecting nearly 10\u0026nbsp;million people worldwide each year[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. VTE is a multifactorial disease caused by the interaction of multiple predisposing factors, which can be transient or persistent, and strong transient predisposing risk factors such as major surgery, prolonged immobilization, and major trauma, accounting for approximately 20% of all VTE events[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In the absence of thromboprophylaxis, the prevalence of DVT after orthopedic surgery varies from 42\u0026ndash;57% after THA and from 41\u0026ndash;85% after TKA[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], and is as high as 60% after lower extremities orthopedic surgery within 2 weeks, of which 14% develop symptoms[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Compared with non-surgical patients, THA or TKA patients had the highest risk of VTE [odds ratio (OR)\u0026thinsp;\u0026gt;\u0026thinsp;10][\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In addition, patients undergoing THA or TKA have a higher risk of VTE due to concurrent risk factors, such as age\u0026thinsp;\u0026gt;\u0026thinsp;60 years, obesity [body mass index (BMI)\u0026thinsp;\u0026gt;\u0026thinsp;30], diabetes, dyslipidemia and inflammatory diseases, and all the above are common risk factors for VTE and osteoarthritis[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough VTE is a serious complication during hospitalization and perioperative period, it is preventable[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Effective anticoagulation prophylaxis for patients undergoing major orthopedic surgery can not only reduce the prevalence and mortality of VTE, but also alleviate pain for patients and reduce medical expenses[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Current preventive measures include primary prevention, physical prevention, and pharmacological prevention, and pharmacological prevention is considered one of the most effective ways to reduce the risk of DVT in lower extremities[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Commonly used anticoagulants in hospital include unfractionated heparin (UFH), low-molecular-weight heparins (LMWHs), fondaparinux sodium and danaparoid[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Among them, LMWHs mainly include enoxaparin (low-molecular-weight heparin sodium) and nadroparin (low-molecular-weight heparin calcium)[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Nadroparin and fondaparinux sodium are two commonly used anticoagulants in clinical practice. However, the efficacy between nadroparin and fondaparinux sodium for prevention of DVT in lower extremities is still unclear.\u003c/p\u003e \u003cp\u003ePrevious studies have found fondaparinux sodium to be superior to enoxaparin in preventing VTE[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Related studies in China have shown that fondaparinux sodium is superior to LMWHs in preventing DVT in patients undergoing major orthopedic surgery[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], but this study does not limit the types of LMWHs. Some investigators have studied the prevention of thrombosis after minimally invasive esophagectomy(MIE) with nadroparin and fondaparinux sodium, and found that the prevalence rate of fondaparinux sodium was lower than that of nadroparin, so the investigators believe that fondaparinux sodium had similar efficacy in the prevention of thrombosis after MIE compared with nadroparin[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], but the sample size was small (N\u0026thinsp;=\u0026thinsp;116). Therefore, we were curious about the performance of nadroparin and fondaparinux sodium in preventing DVT in lower extremities after joint arthroplasty.\u003c/p\u003e \u003cp\u003eThe aim of this study was to retrospectively study the data of patients undergoing THA and TKA in the Second Affiliated Hospital of Wenzhou Medical University, in order to compare the prevalence of VTE with nadroparin and fondaparinux sodium for the prevention of VTE after THA and TKA.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population\u003c/h2\u003e \u003cp\u003eThis study retrospectively analyzed 572 patients who underwent THA and TKA in the Department of Orthopedics of the Second Affiliated Hospital of Wenzhou Medical University from December 2021 to August 2022.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eInclusion and Exclusion Criteria\u003c/h2\u003e \u003cp\u003e The inclusion criteria in our study were: (i) patients who were admitted to our hospital from December 2021 to August 2022; (ii) patients who underwent THA or TKA during hospitalization; (iii) ultrasonography of lower extremity veins was performed before and after operation; (iv) no deep venous thrombosis occurred before operation; (v) nadroparin and fondaparinux sodium was used for postoperative prophylaxis; (vi) patients agree to receive anticoagulant therapy to prevent thrombosis and submit signed informed consent.\u003c/p\u003e \u003cp\u003eThe exclusion criteria were as follows: (i) deep vein thrombosis had occurred before operation; (ii) no ultrasonic examination of lower extremity vein was performed during hospitalization; (iii) anticoagulants other than nadroparin and fondaparinux sodium were used; (iv) patients refused to accept anticoagulant therapy; (v) patients with contraindications for anticoagulation, such as patients with a history of allergy to anticoagulants, acute bacterial endocarditis, thrombocytopenia, fresh bleeding, stroke within 3 months.\u003c/p\u003e \u003cp\u003e We reviewed a total of 676 patients who underwent THA and TKA in the Department of Orthopedics of the Second Affiliated Hospital of Wenzhou Medical University from December 2021 to August 2022. According to the inclusion criteria and exclusion criteria, 104 patients were excluded, and a total of 572 patients were finally included in this study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eData Collection\u003c/h2\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003eAdministration of Anticoagulants\u003c/h2\u003e \u003cp\u003eAll admitted patients routinely assessed thromboembolic risk using a scoring scale. We also assessed patients for contraindications to anticoagulation. For patients with no contraindication to anticoagulation, Nadroparin (Fraxiparine, GlaxoSmithKline, UK) or Fondaparinux Sodium (Hengrui, Jiangsu, China) was administered subcutaneously on the first postoperative day to prevent DVT. Anticoagulant therapy began 12\u0026ndash;24 hours after operation and continued until discharge. In details, the nadroparin was applied as follows: 0.4 mL (4100AxaIU) per day, subcutaneous injection for 14 days beginning 24 h after discontinuation of anesthesia; The fondaparinux sodium was applied as follows: 0.25 mg per day, subcutaneous injection for 14 days beginning 24 h after discontinuation of anesthesia.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eDiagnosis of DVT\u003c/h2\u003e \u003cp\u003eDVT was diagnosed according to the criteria of Fraser et al.[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Doppler ultrasound was used to diagnose DVT. The patients were examined on the second day preoperatively and postoperatively.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eGeneral Characteristics\u003c/h2\u003e \u003cp\u003eWe collected general information (gender, age, body mass index, etc.), current medical history, past medical history (diabetes, hypertension, coronary heart disease), postoperative Caprini score, drug precautions, surgery-related information (surgical methods, anesthesia methods, etc.), thrombosis prevalence (whether thrombosis occurred). The outcome variable was the occurrence of nosocomial thrombosis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eThe Statistical Package for Social Sciences (SPSS) software version 25 (SPSS, Armonk, NY, USA) was used for statistical analysis. The Shapiro-Wilks test was used to assess the distribution of the data. Continuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. Student's t-test was used for parametric analysis of continuous variables and Mann-Whitney U test was used for nonparametric analysis of continuous variables. Chi-square test or Fisher's exact test was used for categorical variables analysis. P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePatients demography\u003c/h2\u003e \u003cp\u003eAfter applying the inclusion and exclusion criteria, a total of 592 THA or TKA patients admitted to our hospital between December 1, 2021 and August 31, 2022 were included. 278 patients received nadroparin and 314 patients received fondaparinux sodium. The demographic data and baseline levels were recorded. The mean age was 68.85\u0026thinsp;\u0026plusmn;\u0026thinsp;10.007 years in nadroparin group while 67.06\u0026thinsp;\u0026plusmn;\u0026thinsp;10.688 years in fondaparinux sodium group. The proportion of males was 37.1% in nadroparin group while 29.9% in fondaparinux sodium group. In addition, we divided all patients into 3 age groups to balance baseline data for age. The detailed information about other clinical characteristics, including comorbidity, type of surgery and type of anesthesia between the two groups is exhibited in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Statistical analysis showed that baseline data were balanced and comparable between the two groups.\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\u003ePatients demography\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNadroparin (n\u0026thinsp;=\u0026thinsp;278)\u003c/p\u003e \u003cp\u003eno. (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFondaparinux Sodium\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;314)\u003c/p\u003e \u003cp\u003eno. (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDVT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23(8.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e47(15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\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 \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.067\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFemale-no.(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e175(62.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e220(70.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMale-no.(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e103(37.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e94(29.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e68.85\u0026thinsp;\u0026plusmn;\u0026thinsp;10.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e67.06\u0026thinsp;\u0026plusmn;\u0026thinsp;10.688\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge stratification\u003c/b\u003e\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 \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e\u0026ge;\u0026thinsp;80\u0026nbsp;year.-no. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e35(12.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25(8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.573\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e65\u0026ndash;79\u0026nbsp;year.-no. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e160(57.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e187(59.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.325\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e༜65\u0026nbsp;year.-no. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e83(29.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e102(32.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.155\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComorbidity\u003c/b\u003e\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 \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHypertension - no. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e131(47.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e141(44.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.589\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eType 2 diabetes - no. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e45(16.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e45(14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.530\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCoronary heart disease - no. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9(3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2(0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eType of surgery\u003c/b\u003e\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 \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.051\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTHA- no. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e108(38.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e98(31.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTKA- no. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e170(61.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e216(68.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eType of anesthesia\u003c/b\u003e\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 \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.243\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGeneral anesthesia- no. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e96(34.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e123(39.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCombined spinal-epidural anesthesia- no. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e182(65.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e191(60.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eDVT prevalence\u003c/h2\u003e \u003cp\u003eA total of 592 patients were included in the study. Among all patients, 70 patients had thrombosis and 522 patients had no thrombosis, and the prevalence of thrombosis was 11.8%. In patients treated with nadroparin, 23 patients experienced thrombosis and 255 patients did not, resulting in a thrombosis rate of 8.3%. Among patients receiving fondaparinux sodium, 47 patients developed thrombosis and 267 patients did not develop thrombosis, with a thrombosis prevalence of 15.0%. Comparing the two anticoagulants, nadroparin showed a lower prevalence of DVT than fondaparinux sodium (8.3% vs. 15.0%, OR\u0026thinsp;=\u0026thinsp;1.952, 95% CI\u0026thinsp;=\u0026thinsp;1.152\u0026ndash;3.307, P\u0026thinsp;=\u0026thinsp;0.012). The DVT prevalence is illustrated in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and its OR and 95%CI is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Among all patients with DVT, 67 patients developed intermuscular venous plexus thrombosis, 1 patient developed anterior tibial vein thrombosis, 1 patient developed posterior tibial vein thrombosis, and 1 patient developed both anterior tibial and posterior tibial thrombosis. The proportion of the 4 types of thrombosis is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\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\u003eDVT prevalence\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNadroparin (n\u0026thinsp;=\u0026thinsp;278)\u003c/p\u003e \u003cp\u003eno. (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFondaparinux Sodium\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;314)\u003c/p\u003e \u003cp\u003eno. (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDVT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23/278(8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47/314(15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.952\u003c/p\u003e \u003cp\u003e(1.152\u0026ndash;3.307)\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\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eSubgroup Analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis of subgroups showed that nadroparin showed a lower prevalence of DVT than fondaparinux sodium in some special patients groups such as female patients (OR\u0026thinsp;=\u0026thinsp;2.258, 95%CI\u0026thinsp;=\u0026thinsp;1.238\u0026ndash;4.119, P\u0026thinsp;=\u0026thinsp;0.007), patients who are 65\u0026ndash;79 years old (OR\u0026thinsp;=\u0026thinsp;2.796, 95%CI\u0026thinsp;=\u0026thinsp;1.360\u0026ndash;5.751, P\u0026thinsp;=\u0026thinsp;0.004), patients with hypertension (OR\u0026thinsp;=\u0026thinsp;2.237, 95%CI\u0026thinsp;=\u0026thinsp;1.016\u0026ndash;4.925, P\u0026thinsp;=\u0026thinsp;0.042), patients who underwent TKA (OR\u0026thinsp;=\u0026thinsp;2.091, 95%CI\u0026thinsp;=\u0026thinsp;1.172\u0026ndash;3.732, P\u0026thinsp;=\u0026thinsp;0.011), and patients who underwent combined spinal-epidural anesthesia (OR\u0026thinsp;=\u0026thinsp;2.490, 95%CI\u0026thinsp;=\u0026thinsp;1.352\u0026ndash;4.587, P\u0026thinsp;=\u0026thinsp;0.003). In other patients groups such as male patients, patients with diabetes mellitus, patients with coronary heart disease, patients who underwent THA, patients who underwent general anesthesia, there was no statistical significance between two drugs in the prevention of VTE. All statistics is illustrated in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\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\u003eSubgroup Analysis of DVT in hospital\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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=\"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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNadroparin (n\u0026thinsp;=\u0026thinsp;278)\u003c/p\u003e \u003cp\u003eno. (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFondaparinux Sodium\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;314)\u003c/p\u003e \u003cp\u003eno. (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003cp\u003e(95%CI)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFemale-no.(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17/175(9.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43/220(19.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.258(1.238\u0026ndash;4.119)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMale-no.(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6/103(5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4/94(4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.860\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge stratification\u003c/b\u003e\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 \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e\u0026ge;\u0026thinsp;80\u0026nbsp;year.-no. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4/35(11.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5/25(20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.582\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e65\u0026ndash;79\u0026nbsp;year.-no. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11/160(6.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32/187(17.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.796(1.360\u0026ndash;5.751)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e༜65\u0026nbsp;year.-no. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8/83(9.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10/102(9.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.970\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComorbidity\u003c/b\u003e\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 \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHypertension - no. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10/131(7.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22/141(15.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.042\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.237(1.016\u0026ndash;4.925)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eType 2 diabetes - no. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2/45(4.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7/45(15.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCoronary heart disease - no. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1/9(11.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0/2(0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eType of surgery\u003c/b\u003e\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 \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTHA- no. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1/108(0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2/98(2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.932\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTKA- no. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19/170(11.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45/216(20.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.091(1.172\u0026ndash;3.732)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eType of anesthesia\u003c/b\u003e\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 \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGeneral anesthesia- no. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6/96(6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8/123(6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.939\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCombined spinal-epidural anesthesia- no. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17/182(9.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39/191(20.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.490(1.352\u0026ndash;4.587)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eVTE prevalence in different type of surgery using the same anticoagulants\u003c/h2\u003e \u003cp\u003eMoreover, we also compared whether there was any difference in the prevalence of DVT after THA and TKA among patients using the same anticoagulants. The results showed that among patients using nadroparin, 3.7% of THA and 11.2% of TKA patients developed DVT. Meanwhile, among patients using fondaparinux, DVT occurred in 2.0% of THA patients and 20.8% of TKA patients. Statistical analysis showed there was statistical significance between the prevalence of DVT of two types of surgery, no matter using which anticoagulants. The statistics is illustrated in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\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\u003eVTE prevalence in different type of surgery using the same anticoagulants\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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=\"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=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eType of surgery\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDVT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eNadroparin\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTHA- no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4(3.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e3.272\u003c/p\u003e \u003cp\u003e(1.082\u0026ndash;9.895)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTKA- no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19(11.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eFondaparinux sodium\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTHA- no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2(2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e༜0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e12.632\u003c/p\u003e \u003cp\u003e(2.998\u0026ndash;53.221)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTKA- no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e45(20.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eDVT is common after major surgery or severe trauma, long-term bedridden, limb immobilization and so on[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Previous study suggests that the prevalence of DVT after orthopedic surgery varies from 42\u0026ndash;57% after THA and from 41\u0026ndash;85% after TKA without thromboprophylaxis[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. In our study, the prevalence of thrombosis was 11.8% with thromboprophylaxis. Although no study has been reported on nadroparin and fondaparinux sodium for the prevention of lower extremity DVT after orthopedic joint replacement surgery, previously. Nevertheless, our results show that the administration of 4100AxaIU nadroparin significantly reduced the prevalence of postoperative DVT compared with the administration of 2.5 mg fondaparinux in patients undergoing THA and TKA.\u003c/p\u003e \u003cp\u003eA number of randomized controlled clinical trials have shown fondaparinux sodium to be superior to enoxaparin in the prevention of VTE following hip fracture, hip replacement, and major knee surgery[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. A real-world study conducted in China retrospectively analyzed the prevention of VTE in patients undergoing major orthopedic surgery and trauma, suggesting that fondaparinux sodium may show better thromboprophylaxis effect in hospitalized patients undergoing major orthopedic surgery or trauma than LMWHs, especially in some special patient populations such as elderly patients, patients with renal impairment, patients with hypertension, etc.[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. However, the LMWHs used in this study did not limit the types of anticoagulants (nadroparin or fondaparinux sodium), which may affect the accuracy of the results. Currently, there still lack studies that systematically review the efficacy and safety of enoxaparin and nadroparin in the prevention of VTE after major orthopedic surgery.\u003c/p\u003e \u003cp\u003eThe American College of Chest Physicians (ACCP) guidelines recommend the use of LMWH, low-dose unfractionated heparin (UFH), vitamin K antagonist (VKA), fondaparinux, apixaban, dabigatran, rivaroxaban, or aspirin for patients who undergo TKA or THA to prevent VTE[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. LMWHs are derived from UFH by chemical or enzymatic depolymerization. Enoxaparin is derived from UFH by benzylation followed by alkaline depolymerization, has an average molecular weight of 3500-5500Da, and contains 10000 International Unit (IU) of anti-Xa factor (AxaIU, WHO compendial units) per ml[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Nadroparin is derived from UFH by nitrous acid depolymerization, has an average molecular weight of 3600-5000Da, and contains 10250 AxaIU per ml[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. LMWHs exert their primary anticoagulant effect by catalyzing AT-mediated inhibition of coagulation factors. The thromboprophylaxis efficacy of LMWHs is equivalent to that of low-dose subcutaneous UFH, with a lower risk of bleeding complications and fewer heparin-related side effects[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Fondaparinux sodium is an artificially isolated natural high-affinity pentasaccharide, synthesized after modification, with a molecular weight of 1728Da[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. UFH and LMWHs bind to antithrombin III (AT III) and enhance its affinity for thrombin and factor Xa, whereas fondaparinux only enhances the affinity of AT III and factor Xa[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Although fondaparinux sodium has been reported to have higher specific anti-Xa activity than LMWHs (approximately 700 units/mg and 100 units/mg, respectively) and a longer half-life after subcutaneous injection than LMWHs (approximately 17h and 4h, respectively), Garcia et al. considered that the validity of low molecular weight heparin as a reference preparation to determine fondaparinux sodium anti-Xa activity is doubtful[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe ACCP recommends LMWHs as optimal pharmacological agents for VTE prophylaxis in patients undergoing THA, TKA, or hip fracture surgery[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. According to Yngve et al., based on moderate-quality evidence, the use of fondaparinux sodium compared with LMWHs does not appear to reduce patient-important VTE events but may increase major bleeding events by nine per 1,000[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Besides, The ACCP advised to use fondaparinux sodium cautiously in patients weighing less than 50 kg and elderly and frail patients because bleeding complications may be increased[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSubgroup analyses identified a lower prevalence of DVT in the nadroparin group than that in the fondaparinux sodium group in some special patients groups, including female patients, patients who are 65\u0026ndash;79 years old, patients with hypertension, patients who underwent TKA, and patients who underwent combined spinal-epidural anesthesia. This may provide an idea for individualized and precise prevention of DVT after THA and TKA. Our results showed that TKA was associated with a higher prevalence of DVT than THA, which is consistent with the results of Senay et al[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In their study, the DVT prevalence rates was 2.2% after TKA and 0.4% after THA during hospitalization. Bedsides, a meta-analysis of 47 studies performed by Januel et al reported that the pooled prevalence rates of VTE for patients treated with LMWHs were 1.4% (95% CI: 1.0\u0026ndash;1.8%) in TKA studies and 0.6% (95% CI: 0.4\u0026ndash;0.8%) in THA studies[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The above studies collected symptomatic VTE, whereas we routinely screened and included many asymptomatic patients with thrombosis, so the prevalence of VTE in our study was higher than the above studies. At the same time, our study found that the prevalence of lower limb intermuscular venous plexus thrombosis was very high, and most of them were asymptomatic. Therefore, attention should be paid to the screening and prevention of lower limb intermuscular venous plexus thrombosis.\u003c/p\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eThe Limitations of This Study\u003c/h2\u003e \u003cp\u003eOur study has several limitations and shortcomings. Firstly, it was a single-center retrospective study and selection bias was unavoidable. Secondly, the sample size included in the study was limited, but it is quite enough for the study. Finally, there is a lack of comparison of the efficacy of different types of LMWHs.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, the use of 4100AxaIU nadroparin may demonstrate better prevention of DVT in the lower extremities after THA and TKA than 2.5 mg fondaparinux sodium, especially in certain populations such as female patients, patients aged 65\u0026ndash;79 years, patients with hypertension, patients underwent TKA, and patients underwent combined spinal-epidural anesthesia. We call for multicenter, large-sample clinical investigations or randomized controlled trials to further elucidate the preventive effects of different anticoagulants on DVT in the lower extremities.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe protocol of this retrospective study was approved by the ethics committees of the Second Affiliated Hospital of Wenzhou Medical University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudy conception and design: XG and PF. Collection and assembly of data: XG, XWJ, RH, ZXL, HLZ and PF. SPSS statistical analysis: XG and PF. Analysis and interpretation of data: XG and PF. Manuscript: XG and PF. All authors reviewed the manuscript and approved the final version to be published.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKhan F, Tritschler T, Kahn SR, Rodger MA. Venous thromboembolism. Lancet. 2021;398:64\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChinese Orthopaedic Association. Prevention of venous thromboembolism after major orthopaedic surgery. Orthop Surg. 2010;2:81\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYu HT, Dylan ML, Lin J, Dubois RW. Hospitals' compliance with prophylaxis guidelines for venous thromboembolism. Am J Health Syst Pharm. 2007;64:69\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHeit JA. Epidemiology of venous thromboembolism. Nat Rev Cardiol. 2015;12:464\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStreiff MB, Haut ER. The CMS ruling on venous thromboembolism after total knee or hip arthroplasty: weighing risks and benefits. JAMA. 2009;301:1063\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFlevas DA, Megaloikonomos PD, Dimopoulos L, Mitsiokapa E, Koulouvaris P, Mavrogenis AF. Thromboembolism prophylaxis in orthopaedics: an update. EFORT Open Rev. 2018;3:136\u0026ndash;48.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFisher WD. Impact of venous thromboembolism on clinical management and therapy after hip and knee arthroplasty. Can J Surg. 2011;54:344\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Oosterom N, Barras M, Bird R, Nusem I, Cottrell N. A Narrative Review of Aspirin Resistance in VTE Prophylaxis for Orthopaedic Surgery. Drugs. 2020;80:1889\u0026ndash;99.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThirugnanam S, Pinto R, Cook DJ, Geerts WH, Fowler RA. Economic analyses of venous thromboembolism prevention strategies in hospitalized patients: a systematic review. Crit Care. 2012;16:R43.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDi Nisio M, van Es N, B\u0026uuml;ller HR. Deep vein thrombosis and pulmonary embolism. Lancet. 2016;388:3060\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\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:e24S\u0026ndash;e43S.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBauer KA, Eriksson BI, Lassen MR, Turpie AG. Steering Committee of the Pentasaccharide in Major Knee Surgery Study. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery. N Engl J Med. 2001;345:1305\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLassen MR, Bauer KA, Eriksson BI, Turpie AG, European Pentasaccharide Elective Surgery Study (EPHESUS) Steering Committee. Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: a randomised double-blind comparison. Lancet. 2002;359:1715\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFu D, Li L, Li Y, Liu X, Chen H, Wu N, et al. Fondaparinux sodium and low molecular weight heparin for venous thromboembolism prophylaxis in Chinese patients with major orthopedic surgery or trauma: a real-world study. BMC Surg. 2022;22:243.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSong J, Xuan L, Wu W, Shen Y, Tan L, Zhong M. Fondaparinux versus nadroparin for thromboprophylaxis following minimally invasive esophagectomy: A randomized controlled trial. Thromb Res. 2018;166:22\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFraser JD, Anderson DR. Venous protocols, techniques, and interpretations of the upper and lower extremities. Radiol Clin North Am. 2004;42:279\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRighini M, Le Gal G, Bounameaux H. Venous thromboembolism diagnosis: unresolved issues. Thromb Haemost. 2015;113:1184\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEriksson BI, Bauer KA, Lassen MR, Turpie AG. Steering Committee of the Pentasaccharide in Hip-Fracture Surgery Study. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery. N Engl J Med. 2001;345:1298\u0026ndash;304.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThiengwittayaporn S, Budhiparama N, Tanavalee C, Tantavisut S, Sorial RM, Li C, et al. Asia-Pacific venous thromboembolism consensus in knee and hip arthroplasty and hip fracture surgery: Part 3. Pharmacological venous thromboembolism prophylaxis. Knee Surg Relat Res. 2021;33:24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBergqvist D. Low-molecular-weight heparin for the prevention of postoperative venous thromboembolism after abdominal surgery: a review. Curr Opin Pulm Med. 2005;11:392\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFalck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S, et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e278S\u0026ndash;e325S.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSenay A, Trottier M, Delisle J, Banica A, Benoit B, Laflamme GY, et al. Incidence of symptomatic venous thromboembolism in 2372 knee and hip replacement patients after discharge: data from a thromboprophylaxis registry in Montreal, Canada. Vasc Health Risk Manag. 2018;14:81\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJanuel JM, Chen G, Ruffieux C, Quan H, Douketis JD, Crowther MA, et al. Symptomatic in-hospital deep vein thrombosis and pulmonary embolism following hip and knee arthroplasty among patients receiving recommended prophylaxis: a systematic review. JAMA. 2012;307:294\u0026ndash;303.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bsur","sideBox":"Learn more about [BMC Surgery](http://bmcsurg.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bsur/default.aspx","title":"BMC Surgery","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Deep Vein Thromboembolism, Nadroparin, Fondaparinux Sodium, Total Hip Arthroplasty, Total Knee Arthroplasty","lastPublishedDoi":"10.21203/rs.3.rs-3825170/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3825170/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjectives: \u003c/strong\u003eTo compare the efficacy of nadroparin and fondaparinux sodium for prevention of deep vein thromboembolism (DVT) in lower extremities after total hip arthroplasty (THA) and total knee arthroplasty (TKA).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods：\u003c/strong\u003eA total of 592 patients were enrolled in the study. Clinical data of patients who underwent total hip arthroplasty (THA) and total knee arthroplasty (TKA) in our hospital from December 2021 to September 2022 were retrospectively collected, which mainly included patients' general information, surgery-related information, and DVT-related information. The patients were categorized into the nadroparin group(n=278) and the fondaparinux sodium group(n=314) according to the types of anticoagulants used. Anticoagulant therapy began 12-24 hours after operation and continued until discharge. DVT prevalence between two groups was compared. The Statistical Package for Social Sciences (SPSS) software version 25 (SPSS, Armonk, NY, USA) was used for statistical analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults：\u003c/strong\u003eThe prevalence of DVT in the nadroparin group and the fondaparinux sodium group was 8.3% (23/278) and 15.0% (47/314), respectively(p=0.012). Statistical analysis showed that nadroparin group showed a lower prevalence of thrombosis than fondaparinux group (OR=1.952, P=0.012). Subgroup analyses showed that nadroparin group had a lower prevalence of DVT than fondaparinux group in some special patients groups such as female patients (OR=2.258, P= 0.007), patients who are 65-79 years old (OR=2.796, P = 0.004), patients with hypertension (OR=2.237, P=0.042), patients who underwent TKA (OR = 2.091, P=0.011), and patients who underwent combined spinal-epidural anesthesia (OR=2.490, P=0.003) (P\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eNadroparinmay have an advantage over fondaparinux sodium in preventing DVT in lower extremities after THA and TKA.\u003c/p\u003e","manuscriptTitle":"Comparison of Efficacy of Nadroparin and Fondaparinux sodium for Prevention of Deep Vein Thromboembolism in lower extremities after Total Hip Arthroplasty and Total Knee Arthroplasty: a retrospective study of 592 patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-03 15:14:32","doi":"10.21203/rs.3.rs-3825170/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-04-17T18:07:57+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-04-08T15:17:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"0003a3d2-115e-4fad-ae8d-07492d9fd194","date":"2024-03-17T18:42:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"d2297d28-a780-4bce-821a-e931d6580e77","date":"2024-02-22T11:57:37+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-02-15T09:36:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"89ef6305-d88c-4a6f-9f77-1ca57dc5fc52","date":"2024-02-07T11:56:49+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-01-16T17:11:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"5d0cebc8-6602-44e7-bc6f-5ff291f23b73","date":"2024-01-02T14:04:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"02a0852b-9cd0-40cf-ad7f-9a6b23071660","date":"2024-01-01T16:05:22+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-01-01T16:03:39+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-01-01T16:01:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2023-12-31T15:00:26+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-12-31T14:58:15+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Surgery","date":"2023-12-31T04:49:23+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bsur","sideBox":"Learn more about [BMC Surgery](http://bmcsurg.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bsur/default.aspx","title":"BMC Surgery","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"30b8c255-c9b0-4495-87df-96a2da84841a","owner":[],"postedDate":"January 3rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-05-06T15:08:19+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-03 15:14:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3825170","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3825170","identity":"rs-3825170","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}