Diagnostic Value of Serum S100B Protein in Anticoagulated Patients Admitted to the Emergency Department for Mild Traumatic Brain Injury

Diagnostic Value of Serum S100B Protein in Anticoagulated Patients Admitted to the Emergency Department for Mild Traumatic Brain Injury | 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 Diagnostic Value of Serum S100B Protein in Anticoagulated Patients Admitted to the Emergency Department for Mild Traumatic Brain Injury Laura Ortiger, Dorian Teissandier, Sebastien Cambier, Romain Durif, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7793527/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Mild traumatic brain injury (mTBI) is a common reason for emergency department visits. Its incidence is increasing, particularly among elderly individuals, who are often receiving anticoagulant therapy. Objective The aim of our study was to evaluate the diagnostic performance of serum S100B protein in anticoagulated patients admitted to the emergency department for mTBI. Methods We conducted a retrospective, single-center, observational study from January 1, 2014, to August 15, 2022, at the Emergency Department of Clermont-Ferrand University Hospital. We included all patients aged over 18 years who presented with mTBI, were on anticoagulant therapy, and underwent both S100B testing and a brain CT scan. Results Among the 46 patients included, 8 (17.4%) had an S100B level 0.10 µg/L. At a threshold of 0.10 µg/L, S100B showed a sensitivity of 100% (95% CI: 29.2–100), specificity of 93% (95% CI: 80.9–98.5), positive predictive value of 50% (95% CI: 11.8–88.2), and negative predictive value of 100% (95% CI: 91.2–100). The area under the ROC curve was 0.94 (95% CI: 86.67–100). Conclusion S100B protein shows promising and robust diagnostic value for evaluating the risk of intracranial bleeding in anticoagulated patients with mTBI. Further prospective studies with larger sample sizes are needed to confirm this hypothesis. Mild Traumatic Brain Injury S100B protein anticoagulants blood biomarkers Figures Figure 1 Figure 2 INTRODUCTION Traumatic brain injury (TBI) is a frequent reason for consultation in the Emergency Department (ED). In Europe, there are approximately 2.5 million cases of TBI annually, 90% of which are classified as mild (mTBI). [1] Following road accidents, falls are the second leading cause of TBIs, predominantly affecting the elderly population. [2] Indeed, mortality and morbidity following a fall increase with age [3], contributing to a rising number of mTBI-related hospital admissions among older adults. [4] In this aging population, the prescription rate of anticoagulants is steadily increasing, especially direct oral anticoagulants (DOACs) used for atrial fibrillation prevention [5]. Vitamin K antagonists (VKAs) are associated with an increased risk of intracranial hemorrhage following mTBI, [6] with an incidence of 9%.[7] DOACs present a comparatively lower risk of post-traumatic intracranial injury.[8] The current gold standard for detecting post-traumatic brain lesions is a non-contrast cranial CT scan.[9] However, over 90% of all CT scans performed—regardless of risk—return normal results. A meta-analysis by Easter et al. [10] estimates the prevalence of severe intracranial lesions to be 7.1% (95% CI: 6.8%–7.4%) in patients with mTBI. Approximately 8% of patients present with non-surgical intracranial hemorrhages, and 1% require neurosurgical intervention.[11] Serum S100B protein testing has been validated in patients with intermediate risk and has demonstrated a 33% reduction in CT scan use [12], resulting in financial savings [13,14], decreased ED wait times, and reduced radiation exposure [15]. To our knowledge, only one recent study has assessed the diagnostic performance of S100B in patients on anticoagulant therapy [16]. The aim of our study is to evaluate the diagnostic performance of S100B in anticoagulated patients admitted to the ED for mTBI. MATERIALS AND METHODS Study design and patients This was a retrospective, observational, single-center study conducted from January 1, 2014, to August 15, 2022, in the Emergency Department of Clermont-Ferrand University Hospital. During this period, we included all patients over 18 years old who presented to the emergency department with an mTBI, were receiving anticoagulant therapy, and underwent both a serum S100B test and a brain CT scan. Anticoagulated patients were retrospectively identified from the RATED database (Registry of patients with Antithrombotic agents admitted to an Emergency Department), maintained in our ED. This registry includes all patients admitted with antithrombotic treatments for any reason since January 2014, with over 40,000 entries. The study was approved by the institutional review board (CPP Sud-Est VI, IRB number: 00008526–2013/CE37) and was declared to the French Data Protection Authority and registered as a clinical trial (NCT02706080, Registered 01 September 2017). From the RATED database, patients on anticoagulants were selected. For patients with multiple entries, only one record was retained. These records were cross-referenced with those who underwent an S100B serum test during the study period. Patients who did not have a brain CT scan were excluded. Serum S100B measurement The decision whether to measure or not S100B was made by the physician in charge of the patient. As now recommended in emergency guidelins, S100B was normaly used for patient with a history of mTBIs defined as a GCS score of 15 with some risk factors such as loss of consciousness and/or amnesia as but not used in patient under anticoagulant agent.[9,17,18] Venous blood samples were collected and centrifuged after a coagulation step to obtain serum. S100B concentrations were determined by electrochemiluminescence immunoassay on a Modular Analytics E170 analyzer (Roche Diagnostics). Each measurement was performed according to the manufacturer’s recommendations.[19] Patients with serum concentrations 0.10 µg/L were considered S100B-positive (S100B + ), as previously well established [20]. Datas For anticoagulated patients who had an S100B measurement, data were collected from the RATED database. This included age, sex, medical history, details of anticoagulant and antithrombotic treatments (name, dose, and indication), and laboratory parameters related to coagulation or that could potentially affect it. The serum S100B values and sampling dates were recorded using the hospital's S100B testing registry from 2014 to 2023. Statistical analysis Statistical analysis was performed using STATA version 15. Given the exploratory nature of this analysis, no correction for multiple comparisons was made. A two-sided type I error rate of 5% was considered statistically significant. Categorical variables were described as frequencies and percentages, while quantitative variables were expressed as mean ± standard deviation or median with interquartile range, depending on distribution. Normality was assessed graphically. The intracranial hemorrhage rate and its 95% confidence interval (CI) were estimated. Groups were compared based on S100B levels, using the 0.1 µg/mL positivity threshold. Chi-square or Fisher's exact test was used for categorical variables, and Wilcoxon test for continuous variables. The relationship between S100B (for a cut-off at 0.10 µg/L) and intracranial hemorrhage was illustrated with a ROC curve and its area under the curve (AUC). RESULTS From January 1, 2014, to August 15, 2022, among the 26,852 patients in the RATED registry, 11,279 were receiving anticoagulants. Among them, 46 patients underwent both S100B testing and a brain CT scan ( Fig. 1 ) . The average age of the study population was 83.44 ± 12.52 years, with an equal gender ratio ( Table 1 ) . Patients in the S100B-negative group were younger than those in the S100B-positive group (78.41 ± 20.12 vs. 84.5 ± 10.37 years, p = 0.75), and the S100B-negative group had a higher proportion of males (62.5% vs. 47.37%, p = 0.70). Table 1 Population Characteristics According to S100B Levels Total Population (N = 46) S100B 0.1 µg/mL (N = 38) p-value Age (mean ± SD) 83.44 ± 12.52 78.41 ± 20.12 84.5 ± 10.37 0.75 Sex - Female, n (%) 23 (50.0) 3 (37.5) 20 (52.63) 0.70 Medical History - Myocardial infarction 6 (13.04) 3 (37.5) 3 (7.89) 0.66 - Hypertension 30 (65.22) 6 (75) 24 (63.16) 0.69 - Atrial fibrillation 34 (73.91) 5 (62.5) 29 (76.32) 0.41 - Diabetes mellitus 10 (21.74) 1 (12.5) 9 (23.68) 0.66 - Gastrointestinal ulcer 1 (2.17) 0 (0) 1 (2.63) 1.00 - Stroke 17 (36.96) 2 (25) 15 (39.47) 0.69 - Dementia 10 (21.74) 2 (25) 8 (21.05) 1.00 - Venous thromboembolism (VTE) 13 (28.26) 4 (50) 9 (23.68) 0.20 - Peripheral artery disease 11 (23.91) 3 (37.5) 8 (21.05) 0.37 - Cancer 15 (32.61) 2 (25) 13 (34.21) 1.00 - Gastrointestinal bleeding 2 (4.35) 0 (0) 2 (5.26) 1.00 - Alcohol use 6 (13.04) 0 (0) 6 (15.79) 0.57 Among the study population, 28 patients (60.87%) were on DOACs, 13 (28.26%) on VKAs, and 5 (10.87%) on LMWH. Table 2 summarizes the distribution of anticoagulants across S100B groups. In the S100B-negative group, 2 patients were also on antiplatelet therapy, compared to 15 patients in the S100B-positive group (25% vs. 39.47%, p = 0.69). Table 2 Distribution of Anticoagulant Therapies According to S100B Levels Total Population (N = 46) S100B 0.1 µg/mL (N = 38) p-value DOACs, n (%) 28 (60.87) 4 (50.0) 24 (63.16) 0.69 - Apixaban 14 (30.43) 4 (50.0) 10 (26.32) 0.22 • Full dose 2 (4.35) 3 (37.5) 0 (0.0) – • Low dose 12 (26.09) 2 (25.0) 10 (26.32) – - Rivaroxaban 9 (19.57) 0 (0.0) 9 (23.68) 0.32 • Full dose 4 (8.70) 0 (0.0) 4 (10.53) – • Low dose 5 (10.87) 0 (0.0) 5 (13.16) – - Dabigatran 5 (10.87) 0 (0.0) 5 (13.16) 0.57 • Full dose 2 (4.35) 0 (0.0) 2 (5.26) – • Low dose 3 (6.52) 0 (0.0) 3 (7.89) – VKA, n (%) 13 (28.26) 3 (37.5) 10 (26.32) 0.67 - Warfarin 5 (10.87) 2 (25.0) 3 (7.89) 0.20 - Fluindione 8 (17.39) 1 (12.5) 7 (18.42) 1.00 LMWH, n (%) 5 (10.87) 1 (12.5) 4 (10.53) 1.00 - Enoxaparin 4 (8.70) 0 (0.0) 4 (10.53) 1.00 • Preventive dose 4 (8.70) 0 (0.0) 4 (10.53) – • Curative dose 0 (0.0) 0 (0.0) 0 (0.0) – - Tinzaparin 1 (2.17) 1 (12.5) 0 (0.0) 0.17 • Preventive dose 0 (0.0) 0 (0.0) 0 (0.0) – • Curative dose 1 (2.17) 1 (12.5) 0 (0.0) – Coagulation-related biological parameters (INR, prothrombin time, and platelet count) were similar between groups ( Table 3 ) . Table 3 Biological Characteristics According to S100B Groups Total (N = 46) S100B 0.1 µg/mL (N = 38) p-value INR (mean ± SD) 1.55 ± 0.57 1.61 ± 0.63 1.54 ± 0.57 0.89 Prothrombin time (%) 62.85 ± 23.21 61 ± 26.80 63.24 ± 22.85 0.84 aPTT (mean ± SD) 1.18 ± 0.22 1.16 ± 0.21 1.19 ± 0.22 0.61 Creatinine (µmol/L) 103.44 ± 85.44 84.26 ± 22.75 106.97 ± 92.27 0.51 Urea (mmol/L) 8.91 ± 5.12 7.1 ± 3.09 9.24 ± 5.38 0.25 CRP (mg/L) 18.99 ± 38.19 30.83 ± 69.81 17.02 ± 31.37 0.52 Fibrinogen (g/L) 4.18 ± 1.33 3.86 ± 1.54 4.24 ± 1.29 0.17 Platelet count (G/L) 230.23 ± 70.06 227.29 ± 93.95 230.78 ± 66.25 0.91 Hemoglobin (g/dL) 13.25 ± 1.34 12.66 ± 1.10 13.37 ± 1.37 0.25 A total of 17 patients (37%) were hospitalized, while 29 (63%) were discharged home ( Table 4 ) . Discharge rates were lower in the S100B-negative group compared to the S100B-positive group (50% vs. 65.8%, p = 0.44). No deaths were reported. Table 4 Clinical Outcomes According to S100B Groups Total (N = 46) S100B 0.1 µg/mL (N = 38) p-value Discharged home, n (%) 29 (63.04%) 4 (50%) 25 (65.79%) 0.44 Hospitalized, n (%) 17 (36.96%) 4 (50%) 13 (34.21%) 0.44 Death, n (%) 0 (0%) 0 (0%) 0 (0%) — Hospital stay (days, mean ± SD) 2.57 ± 4.45 4.63 ± 5.29 2.11 ± 4.19 0.19 Intracranial hemorrhage, n (%) 3 (6.52%) 0 (0%) 3 (7.89%) 1.00 At the threshold of 0.1 µg/L, the S100B test showed a sensitivity of 100% (95% CI: 29.2–100), specificity of 93% (95% CI: 80.9–98.5), positive predictive value of 50% (95% CI: 11.8–88.2), and negative predictive value of 100% (95% CI: 91.2–100) for detecting intracranial hemorrhage in anticoagulated patients with mTBI. The AUC was 0.94 (95% CI: 86.67–100) (Fig. 2 ). Of the 46 patients, 8 (17.4%) had a negative S100B result with no hemorrhage, suggesting a potential CT scan reduction rate of 17.4%. DISCUSSION To our knowledge, this is the second published study evaluating the relevance of serum S100B protein measurement in elderly patients on anticoagulants with mild traumatic brain injury (mTBI). We demonstrated that a serum S100B value below 0.10 µg/L allows for excluding intracranial hemorrhage in this population, with an area under the curve (AUC) of 0.94 and a negative predictive value (NPV) of 100% (95% CI: 91.2–100). The clinical performance observed in our study is similar to that reported by Poislane et al. [16] in terms of sensitivity and NPV, and even superior in terms of specificity (93% vs. 25%). This difference may be explained by variations in the study designs. Furthermore, the use of S100B in our study population could have led to a 17.4% reduction in CT scans. These results contrast with the findings of Wania et al., who did not identify S100B concentration or anticoagulant therapy as a factor for forgoing brain imaging in elderly patients.[21] The patients in our study were overall homogeneous and comparable in terms of demographic and biological characteristics. However, the average age in our cohort (83.4 years) was higher than in studies on patients with intermediate risk of intracranial bleeding after mTBI, such as the study by Allouchery et al. [22] where the mean age was 51 years. In that study, patients aged 65 years or older had significantly higher plasma levels and positivity rates of S100B. They found 82.3% of positive S100B results, implying 17.7% were negative corresponding to the percentage of avoidable CT scans in that age group. This figure is in line with our findings, which showed 17.4% of patients with negative S100B, suggesting potential for imaging reduction. The idea of using a higher threshold tailored to older populations has been proposed [23] as in Poislane et al.’s study.[24] But in the absence of a validated consensus, we adhered to the currently established cutoff of 0.10 µg/L. In our study, 3 patients (6.5%) on anticoagulants (1 on rivaroxaban, 1 on apixaban and aspirin, and 1 on fluindione and aspirin) with mTBI had intracranial hemorrhages. Their mean age was 85.6 years, and all had a history of hypertension and atrial fibrillation. None had a prior history of anticoagulant-related bleeding. All were hospitalized, and none died. In the literature, the rate of intracranial hemorrhage after mTBI ranges from 2.8% to 9.8% for patients on DOACs and from 9% to 17.3% for those on VKAs [25–30]. Our hemorrhage rate appears consistent with published data. Notably, 2 of the 3 patients were on a combination of anticoagulants and antiplatelets, which is known to significantly increase the risk of major bleeding, including intracranial hemorrhage. For example, the meta-analysis by Testa et al. [31] showed that warfarin plus aspirin reduced major cardiovascular events but doubled the risk of major bleeding compared to aspirin alone. Similarly, Costa et al. [32] found that in patients with peripheral artery disease, the combination of a DOAC and aspirin significantly reduced limb-related events (OR 0.70 [0.61–0.83], p < 0.001), but increased major bleeding risk (OR 1.46 [1.16–1.84], p = 0.001). Despite our patients being anticoagulated, the diagnostic performance of S100B in mild traumatic brain injury remained high: 100% sensitivity, 93% specificity, 50% positive predictive value (PPV), and 100% NPV for the detection of brain lesions. Our findings are consistent with the meta-analysis by Karamian A et al. which pooled 32 studies assessing S100B levels measured within 3 hours of mTBI to predict CT findings.[33] In our study, the AUC for S100B reached 0.94 in anticoagulated patients. It may be valuable to investigate, in this elderly and anticoagulated population, the diagnostic performance of combined biomarkers such as GFAP and UCH-L1, which are currently validated for use in patients presenting to the ED after mTBI. [9] Our study has several limitations. First, only 46 patients were included, resulting in limited statistical power. This small sample size is primarily due to the fact that S100B measurement is not routinely recommended in anticoagulated patients. Therefore, the sample reflects good adherence by the Triage Nurse (IOA) to the current sampling protocol in place at the Emergency Department of Clermont-Ferrand University Hospital. In most cases, S100B testing in these patients was likely performed due to a lack of awareness of their anticoagulation status by the triage nurse at the time of admission. Nonetheless, the S100B result did not impact the quality of care, as a brain CT scan was systematically ordered by the treating physician regardless of the S100B result, including in S100B-negative cases. The physicians managing these patients demonstrated appropriate knowledge of the clinical guidelines concerning the use of S100B protein. Moreover, the small sample size is not necessarily a major concern in evaluating the diagnostic performance of S100B, given the strong reliability of this biomarker in the context of mild traumatic brain injury (mTBI). Second, our study was monocentric and conducted in a single hospital, which may limit the generalizability of the findings. However, it ensured consistency in patient management protocols for those presenting with anticoagulant-related head trauma. Finally, as this was a retrospective study, we can only propose hypotheses regarding the validity of S100B measurement in anticoagulated patients with mTBI. Nevertheless, to our knowledge, this is the second published study specifically focusing on the role of S100B protein in this growing patient population. The number of anticoagulated individuals continues to increase (39), particularly among the elderly, who are highly susceptible to falls—a major public health concern affecting an estimated 26.5% of older adults worldwide (95% CI: 23.4–29.8%).[34] CONCLUSION Our study is one of the first to evaluate the diagnostic value of serum S100B protein in elderly patients receiving anticoagulant therapy and admitted to the emergency department for mild traumatic brain injury. At the established threshold of 0.10 µg/L, S100B protein demonstrated excellent diagnostic accuracy for assessing the risk of intracranial bleeding, with a negative predictive value of 100% and an area under the curve (AUC) of 0.94. Abbreviations • mTBI: Mild Traumatic Brain Injury • CT: Computed Tomography • OR: Odds Ratio • ED: Emergency Department • NPV: Negative Predictive Value • IQR: Interquartile Range • SD: Standard Deviation • DOAC: Direct Oral Anticoagulant • VKA: Vitamin K Antagonist • GCS: Glasgow Coma Scale • LMWH: Low Molecular Weight Heparin • ICH: Intracranial Hemorrhage • INR: International Normalized Ratio • WHO: World Health Organization • S100B: S100β Protein • TBI: Traumatic Brain Injury • AUC: Area Under the Curve • PPV: Positive Predictive Value Declarations Ethics approval and consent to participate The RATED Registry was approved by the institutional review board (CPP Sud-Est VI, IRB number: 00008526–2013/CE37) and was declared to the French Data Protection Authority and registered as a clinical trial (NCT02706080, Registered 01 September 2017). Consent for publication Not Applicable Availability of data and materials The datasets generated and analyzed during this study are not publicly available but may be obtained from the corresponding author upon reasonable request. Competing Interests FM has served as a consultant for Bayer HealthCare Pharmaceuticals and Sanofi, been a speaker for Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim, Daiichi-Sankyo, Leo-pharma, Pfizer, Sanofi, and Abbott, and has received grants from Sanofi, Bayer HealthCare, and LFB VS has served as consultant for Roche Diagnostics, Abbott Diagnostics, Biomérieux, Diasorin, and Snibe. Authors authors declare that they have no competing interests Funding This research did not receive any specific funding from public, commercial, or not-for-profit sectors. Authors' contributions LO, FM: study design, data analysis and interpretation, data collection, manuscript drafting DT: data interpretation, data collection, manuscript approval SC: statistical analysis, data interpretation, manuscript approval RD, DR: data collection, data interpretation, manuscript approval JS, DB, VS: study design, data analysis and interpretation, manuscript approval Acknowledgements All authors had full access to all the data (including statistical reports and tables) and take full responsibility for data integrity and accuracy. All authors critically revised and approved the final version of the manuscript submitted for publication. References Maas AIR, Menon DK, David Adelson PD, Andelic N, Bell MJ, Belli A, et al. Traumatic brain injury: Integrated approaches to improve prevention, clinical care, and research. Lancet Neurol. 2017;16:987–1048. https://doi.org/10.1016/S1474-4422(17)30371-X Tagliaferri F, Compagnone C, Korsic M, Servadei F, Kraus J. 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Diagnostic performance of S100B assay for intracranial hemorrhage detection in patients with mild traumatic brain injury under antiplatelet or anticoagulant therapy. Sci Rep. 2025;15:5741. https://doi.org/10.1038/s41598-025-89927-9 Riccardi A, Spinola B, Minuto P, Ghinatti M, Guiddo G, Malerba M, et al. Intracranial complications after minor head injury (MHI) in patients taking vitamin K antagonists (VKA) or direct oral anticoagulants (DOACs). Am J Emerg Med. Elsevier Inc; 2017;35:1317–9. https://doi.org/10.1016/j.ajem.2017.03.072 Turcato G, Zannoni M, Zaboli A, Zorzi E, Ricci G, Pfeifer N, et al. Direct Oral Anticoagulant Treatment and Mild Traumatic Brain Injury: Risk of Early and Delayed Bleeding and the Severity of Injuries Compared with Vitamin K Antagonists. J Emerg Med. Elsevier USA; 2019;57:817–24. https://doi.org/10.1016/j.jemermed.2019.09.007 Turcato G, Zaboli A, Zannoni M, Ricci G, Zorzi E, Ciccariello L, et al. Risk factors associated with intracranial bleeding and neurosurgery in patients with mild traumatic brain injury who are receiving direct oral anticoagulants. Am J Emerg Med. W.B. Saunders; 2021;43:180–5. https://doi.org/10.1016/j.ajem.2020.02.046 Cipriano A, Pecori A, Bionda AE, Bardini M, Frassi F, Leoli F, et al. Intracranial hemorrhage in anticoagulated patients with mild traumatic brain injury: significant differences between direct oral anticoagulants and vitamin K antagonists. Intern Emerg Med. Springer-Verlag Italia s.r.l.; 2018;13:1077–87. https://doi.org/10.1007/S11739-018-1806-1/METRICS Santing JAL, Hopman JH, Verheul RJ, van der Naalt J, van den Brand CL, Jellema K. Clinical value of S100B in detecting intracranial injury in elderly patients with mild traumatic brain injury. Injury. Elsevier; 2024;55:111313. https://doi.org/10.1016/J.INJURY.2024.111313 Alrajhi KN, Perry JJ, Forster AJ. Intracranial bleeds after minor and minimal head injury in patients on warfarin. J Emerg Med. Elsevier USA; 2015;48:137–42. https://doi.org/10.1016/j.jemermed.2014.08.016 Testa L, Zoccai GB, Porto I, Trotta G, Agostoni P, Andreotti F, et al. Adjusted Indirect Meta-Analysis of Aspirin Plus Warfarin at International Normalized Ratios 2 to 3 Versus Aspirin Plus Clopidogrel After Acute Coronary Syndromes. Am J Cardiol. 2007;99:1637–42. https://doi.org/10.1016/j.amjcard.2007.01.052 Costa G, Gonçalves L, Teixeira R. The efficacy and safety of direct oral anticoagulants plus aspirin in symptomatic lower extremity peripheral arterial disease: a systematic review and meta-analysis of randomized controlled trials. J Thromb Thrombolysis. J Thromb Thrombolysis; 2021;52:904–13. https://doi.org/10.1007/S11239-021-02417-3 Karamian A, Farzaneh H, Khoshnoodi M, Maleki N, Karamian A, Stufflebeam S, et al. Diagnostic Accuracy of S100B in Predicting Intracranial Abnormalities on CT Imaging Following Mild Traumatic Brain Injury: A Systematic Review and Meta-analysis. Neurocrit Care. 2025;42:1025–42. https://doi.org/10.1007/s12028-024-02189-7 Salari N, Darvishi N, Ahmadipanah M, Shohaimi S, Mohammadi M. Global prevalence of falls in the older adults: a comprehensive systematic review and meta-analysis. J Orthop Surg. BioMed Central Ltd; 2022;17. https://doi.org/10.1186/s13018-022-03222-1 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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1","display":"","copyAsset":false,"role":"figure","size":57764,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlow Chart\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7793527/v1/750bc343674322e15b752b0e.png"},{"id":94397629,"identity":"e5b96fe3-afbe-45b9-b138-6dccd9788cc0","added_by":"auto","created_at":"2025-10-27 13:56:44","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":68209,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eROC Curve\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7793527/v1/df2edb2b794dd787ab5788f9.png"},{"id":103488954,"identity":"1e6bf2b3-5713-4539-9657-e8bc26f2df06","added_by":"auto","created_at":"2026-02-26 09:28:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":916468,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7793527/v1/24a8cff4-22ec-4ce6-926b-bbc892854da4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Diagnostic Value of Serum S100B Protein in Anticoagulated Patients Admitted to the Emergency Department for Mild Traumatic Brain Injury","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eTraumatic brain injury (TBI) is a frequent reason for consultation in the Emergency Department (ED). In Europe, there are approximately 2.5\u0026nbsp;million cases of TBI annually, 90% of which are classified as mild (mTBI). [1] Following road accidents, falls are the second leading cause of TBIs, predominantly affecting the elderly population. [2] Indeed, mortality and morbidity following a fall increase with age [3], contributing to a rising number of mTBI-related hospital admissions among older adults. [4]\u003c/p\u003e\u003cp\u003eIn this aging population, the prescription rate of anticoagulants is steadily increasing, especially direct oral anticoagulants (DOACs) used for atrial fibrillation prevention [5]. Vitamin K antagonists (VKAs) are associated with an increased risk of intracranial hemorrhage following mTBI, [6] with an incidence of 9%.[7] DOACs present a comparatively lower risk of post-traumatic intracranial injury.[8]\u003c/p\u003e\u003cp\u003eThe current gold standard for detecting post-traumatic brain lesions is a non-contrast cranial CT scan.[9] However, over 90% of all CT scans performed\u0026mdash;regardless of risk\u0026mdash;return normal results. A meta-analysis by Easter et al. [10] estimates the prevalence of severe intracranial lesions to be 7.1% (95% CI: 6.8%\u0026ndash;7.4%) in patients with mTBI. Approximately 8% of patients present with non-surgical intracranial hemorrhages, and 1% require neurosurgical intervention.[11]\u003c/p\u003e\u003cp\u003eSerum S100B protein testing has been validated in patients with intermediate risk and has demonstrated a 33% reduction in CT scan use [12], resulting in financial savings [13,14], decreased ED wait times, and reduced radiation exposure [15]. To our knowledge, only one recent study has assessed the diagnostic performance of S100B in patients on anticoagulant therapy [16].\u003c/p\u003e\u003cp\u003eThe aim of our study is to evaluate the diagnostic performance of S100B in anticoagulated patients admitted to the ED for mTBI.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy design and patients\u003c/h2\u003e\u003cp\u003eThis was a retrospective, observational, single-center study conducted from January 1, 2014, to August 15, 2022, in the Emergency Department of Clermont-Ferrand University Hospital.\u003c/p\u003e\u003cp\u003eDuring this period, we included all patients over 18 years old who presented to the emergency department with an mTBI, were receiving anticoagulant therapy, and underwent both a serum S100B test and a brain CT scan.\u003c/p\u003e\u003cp\u003eAnticoagulated patients were retrospectively identified from the RATED database (Registry of patients with Antithrombotic agents admitted to an Emergency Department), maintained in our ED. This registry includes all patients admitted with antithrombotic treatments for any reason since January 2014, with over 40,000 entries. The study was approved by the institutional review board (CPP Sud-Est VI, IRB number: 00008526\u0026ndash;2013/CE37) and was declared to the French Data Protection Authority and registered as a clinical trial (NCT02706080, Registered 01 September 2017).\u003c/p\u003e\u003cp\u003eFrom the RATED database, patients on anticoagulants were selected. For patients with multiple entries, only one record was retained. These records were cross-referenced with those who underwent an S100B serum test during the study period. Patients who did not have a brain CT scan were excluded.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eSerum S100B measurement\u003c/h3\u003e\n\u003cp\u003eThe decision whether to measure or not S100B was made by the physician in charge of the patient. As now recommended in emergency guidelins, S100B was normaly used for patient with a history of mTBIs defined as a GCS score of 15 with some risk factors such as loss of consciousness and/or amnesia as but not used in patient under anticoagulant agent.[9,17,18]\u003c/p\u003e\u003cp\u003eVenous blood samples were collected and centrifuged after a coagulation step to obtain serum. S100B concentrations were determined by electrochemiluminescence immunoassay on a Modular Analytics E170 analyzer (Roche Diagnostics). Each measurement was performed according to the manufacturer\u0026rsquo;s recommendations.[19] Patients with serum concentrations\u0026thinsp;\u0026lt;\u0026thinsp;0.10 \u0026micro;g/L were considered S100B-negative (S100B\u003csup\u003e\u0026minus;\u003c/sup\u003e) and those with serum concentrations\u0026thinsp;\u0026gt;\u0026thinsp;0.10 \u0026micro;g/L were considered S100B-positive (S100B\u003csup\u003e+\u003c/sup\u003e), as previously well established [20].\u003c/p\u003e\n\u003ch3\u003eDatas\u003c/h3\u003e\n\u003cp\u003eFor anticoagulated patients who had an S100B measurement, data were collected from the RATED database. This included age, sex, medical history, details of anticoagulant and antithrombotic treatments (name, dose, and indication), and laboratory parameters related to coagulation or that could potentially affect it.\u003c/p\u003e\u003cp\u003eThe serum S100B values and sampling dates were recorded using the hospital's S100B testing registry from 2014 to 2023.\u003c/p\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eStatistical analysis was performed using STATA version 15. Given the exploratory nature of this analysis, no correction for multiple comparisons was made. A two-sided type I error rate of 5% was considered statistically significant.\u003c/p\u003e\u003cp\u003eCategorical variables were described as frequencies and percentages, while quantitative variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median with interquartile range, depending on distribution. Normality was assessed graphically. The intracranial hemorrhage rate and its 95% confidence interval (CI) were estimated.\u003c/p\u003e\u003cp\u003eGroups were compared based on S100B levels, using the 0.1 \u0026micro;g/mL positivity threshold. Chi-square or Fisher's exact test was used for categorical variables, and Wilcoxon test for continuous variables. The relationship between S100B (for a cut-off at 0.10 \u0026micro;g/L) and intracranial hemorrhage was illustrated with a ROC curve and its area under the curve (AUC).\u003c/p\u003e\u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eFrom January 1, 2014, to August 15, 2022, among the 26,852 patients in the RATED registry, 11,279 were receiving anticoagulants. Among them, 46 patients underwent both S100B testing and a brain CT scan \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe average age of the study population was 83.44\u0026thinsp;\u0026plusmn;\u0026thinsp;12.52 years, with an equal gender ratio \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. Patients in the S100B-negative group were younger than those in the S100B-positive group (78.41\u0026thinsp;\u0026plusmn;\u0026thinsp;20.12 vs. 84.5\u0026thinsp;\u0026plusmn;\u0026thinsp;10.37 years, p\u0026thinsp;=\u0026thinsp;0.75), and the S100B-negative group had a higher proportion of males (62.5% vs. 47.37%, p\u0026thinsp;=\u0026thinsp;0.70).\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\u003ePopulation Characteristics According to S100B Levels\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=\"char\" char=\".\" 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\u003eTotal Population (N\u0026thinsp;=\u0026thinsp;46)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eS100B\u0026thinsp;\u0026lt;\u0026thinsp;0.1 \u0026micro;g/mL (N\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eS100B\u0026thinsp;\u0026gt;\u0026thinsp;0.1 \u0026micro;g/mL (N\u0026thinsp;=\u0026thinsp;38)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\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\u003eAge (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e83.44\u0026thinsp;\u0026plusmn;\u0026thinsp;12.52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e78.41\u0026thinsp;\u0026plusmn;\u0026thinsp;20.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e84.5\u0026thinsp;\u0026plusmn;\u0026thinsp;10.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.75\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSex\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- Female, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23 (50.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (37.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e20 (52.63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.70\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMedical History\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- Myocardial infarction\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (13.04)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (37.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (7.89)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.66\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Hypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30 (65.22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e24 (63.16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.69\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Atrial fibrillation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e34 (73.91)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (62.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e29 (76.32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.41\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Diabetes mellitus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (21.74)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (12.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9 (23.68)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.66\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Gastrointestinal ulcer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (2.17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (2.63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Stroke\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (36.96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15 (39.47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.69\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Dementia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (21.74)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (21.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Venous thromboembolism (VTE)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (28.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9 (23.68)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.20\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Peripheral artery disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (23.91)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (37.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (21.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.37\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (32.61)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13 (34.21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Gastrointestinal bleeding\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (4.35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (5.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Alcohol use\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (13.04)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (15.79)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.57\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\u003eAmong the study population, 28 patients (60.87%) were on DOACs, 13 (28.26%) on VKAs, and 5 (10.87%) on LMWH. Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e summarizes the distribution of anticoagulants across S100B groups. In the S100B-negative group, 2 patients were also on antiplatelet therapy, compared to 15 patients in the S100B-positive group (25% vs. 39.47%, p\u0026thinsp;=\u0026thinsp;0.69).\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\u003eDistribution of Anticoagulant Therapies According to S100B Levels\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=\"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\u003eTotal Population (N\u0026thinsp;=\u0026thinsp;46)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eS100B\u0026thinsp;\u0026lt;\u0026thinsp;0.1 \u0026micro;g/mL (N\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eS100B\u0026thinsp;\u0026gt;\u0026thinsp;0.1 \u0026micro;g/mL (N\u0026thinsp;=\u0026thinsp;38)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\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\u003eDOACs, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e28 (60.87)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4 (50.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e24 (63.16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.69\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Apixaban\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e14 (30.43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4 (50.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e10 (26.32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.22\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026bull; Full dose\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2 (4.35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3 (37.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026bull; Low dose\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e12 (26.09)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2 (25.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e10 (26.32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Rivaroxaban\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e9 (19.57)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9 (23.68)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.32\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026bull; Full dose\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4 (8.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4 (10.53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026bull; Low dose\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5 (10.87)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5 (13.16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Dabigatran\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5 (10.87)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5 (13.16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.57\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026bull; Full dose\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2 (4.35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2 (5.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026bull; Low dose\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3 (6.52)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3 (7.89)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eVKA, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e13 (28.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3 (37.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e10 (26.32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.67\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Warfarin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5 (10.87)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2 (25.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3 (7.89)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.20\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Fluindione\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e8 (17.39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1 (12.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e7 (18.42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLMWH, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5 (10.87)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1 (12.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4 (10.53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Enoxaparin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4 (8.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4 (10.53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026bull; Preventive dose\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4 (8.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4 (10.53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026bull; Curative dose\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Tinzaparin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1 (2.17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1 (12.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.17\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026bull; Preventive dose\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026bull; Curative dose\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1 (2.17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1 (12.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026ndash;\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\u003eCoagulation-related biological parameters (INR, prothrombin time, and platelet count) were similar between groups \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e)\u003c/b\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\u003eBiological Characteristics According to S100B Groups\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=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" 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\u003eTotal\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;46)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eS100B\u0026thinsp;\u0026lt;\u0026thinsp;0.1 \u0026micro;g/mL\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eS100B\u0026thinsp;\u0026gt;\u0026thinsp;0.1 \u0026micro;g/mL\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;38)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\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\u003eINR (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e1.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e1.61\u0026thinsp;\u0026plusmn;\u0026thinsp;0.63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e1.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.89\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eProthrombin time (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e62.85\u0026thinsp;\u0026plusmn;\u0026thinsp;23.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e61\u0026thinsp;\u0026plusmn;\u0026thinsp;26.80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e63.24\u0026thinsp;\u0026plusmn;\u0026thinsp;22.85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.84\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eaPTT (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e1.18\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e1.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e1.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.61\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCreatinine (\u0026micro;mol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e103.44\u0026thinsp;\u0026plusmn;\u0026thinsp;85.44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e84.26\u0026thinsp;\u0026plusmn;\u0026thinsp;22.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e106.97\u0026thinsp;\u0026plusmn;\u0026thinsp;92.27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.51\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUrea (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e8.91\u0026thinsp;\u0026plusmn;\u0026thinsp;5.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e7.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e9.24\u0026thinsp;\u0026plusmn;\u0026thinsp;5.38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.25\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCRP (mg/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e18.99\u0026thinsp;\u0026plusmn;\u0026thinsp;38.19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e30.83\u0026thinsp;\u0026plusmn;\u0026thinsp;69.81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e17.02\u0026thinsp;\u0026plusmn;\u0026thinsp;31.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.52\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFibrinogen (g/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e4.18\u0026thinsp;\u0026plusmn;\u0026thinsp;1.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e3.86\u0026thinsp;\u0026plusmn;\u0026thinsp;1.54\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e4.24\u0026thinsp;\u0026plusmn;\u0026thinsp;1.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.17\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlatelet count (G/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e230.23\u0026thinsp;\u0026plusmn;\u0026thinsp;70.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e227.29\u0026thinsp;\u0026plusmn;\u0026thinsp;93.95\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e230.78\u0026thinsp;\u0026plusmn;\u0026thinsp;66.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.91\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemoglobin (g/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e13.25\u0026thinsp;\u0026plusmn;\u0026thinsp;1.34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e12.66\u0026thinsp;\u0026plusmn;\u0026thinsp;1.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e13.37\u0026thinsp;\u0026plusmn;\u0026thinsp;1.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.25\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\u003eA total of 17 patients (37%) were hospitalized, while 29 (63%) were discharged home \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. Discharge rates were lower in the S100B-negative group compared to the S100B-positive group (50% vs. 65.8%, p\u0026thinsp;=\u0026thinsp;0.44). No deaths were reported.\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\u003eClinical Outcomes According to S100B Groups\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\u003eTotal (N\u0026thinsp;=\u0026thinsp;46)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eS100B\u0026thinsp;\u0026lt;\u0026thinsp;0.1 \u0026micro;g/mL (N\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eS100B\u0026thinsp;\u0026gt;\u0026thinsp;0.1 \u0026micro;g/mL (N\u0026thinsp;=\u0026thinsp;38)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\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\u003eDischarged home, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29 (63.04%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (50%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e25 (65.79%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.44\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHospitalized, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (36.96%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (50%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13 (34.21%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.44\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDeath, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHospital stay (days, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.57\u0026thinsp;\u0026plusmn;\u0026thinsp;4.45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.63\u0026thinsp;\u0026plusmn;\u0026thinsp;5.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.11\u0026thinsp;\u0026plusmn;\u0026thinsp;4.19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.19\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntracranial hemorrhage, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (6.52%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (7.89%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.00\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\u003eAt the threshold of 0.1 \u0026micro;g/L, the S100B test showed a sensitivity of 100% (95% CI: 29.2\u0026ndash;100), specificity of 93% (95% CI: 80.9\u0026ndash;98.5), positive predictive value of 50% (95% CI: 11.8\u0026ndash;88.2), and negative predictive value of 100% (95% CI: 91.2\u0026ndash;100) for detecting intracranial hemorrhage in anticoagulated patients with mTBI. The AUC was 0.94 (95% CI: 86.67\u0026ndash;100) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Of the 46 patients, 8 (17.4%) had a negative S100B result with no hemorrhage, suggesting a potential CT scan reduction rate of 17.4%.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eTo our knowledge, this is the second published study evaluating the relevance of serum S100B protein measurement in elderly patients on anticoagulants with mild traumatic brain injury (mTBI). We demonstrated that a serum S100B value below 0.10 \u0026micro;g/L allows for excluding intracranial hemorrhage in this population, with an area under the curve (AUC) of 0.94 and a negative predictive value (NPV) of 100% (95% CI: 91.2\u0026ndash;100).\u003c/p\u003e\u003cp\u003eThe clinical performance observed in our study is similar to that reported by Poislane et al. [16] in terms of sensitivity and NPV, and even superior in terms of specificity (93% vs. 25%). This difference may be explained by variations in the study designs. Furthermore, the use of S100B in our study population could have led to a 17.4% reduction in CT scans. These results contrast with the findings of Wania et al., who did not identify S100B concentration or anticoagulant therapy as a factor for forgoing brain imaging in elderly patients.[21]\u003c/p\u003e\u003cp\u003eThe patients in our study were overall homogeneous and comparable in terms of demographic and biological characteristics. However, the average age in our cohort (83.4 years) was higher than in studies on patients with intermediate risk of intracranial bleeding after mTBI, such as the study by Allouchery et al. [22] where the mean age was 51 years. In that study, patients aged 65 years or older had significantly higher plasma levels and positivity rates of S100B. They found 82.3% of positive S100B results, implying 17.7% were negative corresponding to the percentage of avoidable CT scans in that age group. This figure is in line with our findings, which showed 17.4% of patients with negative S100B, suggesting potential for imaging reduction. The idea of using a higher threshold tailored to older populations has been proposed [23] as in Poislane et al.\u0026rsquo;s study.[24] But in the absence of a validated consensus, we adhered to the currently established cutoff of 0.10 \u0026micro;g/L.\u003c/p\u003e\u003cp\u003eIn our study, 3 patients (6.5%) on anticoagulants (1 on rivaroxaban, 1 on apixaban and aspirin, and 1 on fluindione and aspirin) with mTBI had intracranial hemorrhages. Their mean age was 85.6 years, and all had a history of hypertension and atrial fibrillation. None had a prior history of anticoagulant-related bleeding. All were hospitalized, and none died. In the literature, the rate of intracranial hemorrhage after mTBI ranges from 2.8% to 9.8% for patients on DOACs and from 9% to 17.3% for those on VKAs [25\u0026ndash;30]. Our hemorrhage rate appears consistent with published data. Notably, 2 of the 3 patients were on a combination of anticoagulants and antiplatelets, which is known to significantly increase the risk of major bleeding, including intracranial hemorrhage. For example, the meta-analysis by Testa et al. [31] showed that warfarin plus aspirin reduced major cardiovascular events but doubled the risk of major bleeding compared to aspirin alone. Similarly, Costa et al. [32] found that in patients with peripheral artery disease, the combination of a DOAC and aspirin significantly reduced limb-related events (OR 0.70 [0.61\u0026ndash;0.83], p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), but increased major bleeding risk (OR 1.46 [1.16\u0026ndash;1.84], p\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003eDespite our patients being anticoagulated, the diagnostic performance of S100B in mild traumatic brain injury remained high: 100% sensitivity, 93% specificity, 50% positive predictive value (PPV), and 100% NPV for the detection of brain lesions. Our findings are consistent with the meta-analysis by Karamian A et al. which pooled 32 studies assessing S100B levels measured within 3 hours of mTBI to predict CT findings.[33] In our study, the AUC for S100B reached 0.94 in anticoagulated patients. It may be valuable to investigate, in this elderly and anticoagulated population, the diagnostic performance of combined biomarkers such as GFAP and UCH-L1, which are currently validated for use in patients presenting to the ED after mTBI. [9]\u003c/p\u003e\u003cp\u003eOur study has several limitations. First, only 46 patients were included, resulting in limited statistical power. This small sample size is primarily due to the fact that S100B measurement is not routinely recommended in anticoagulated patients. Therefore, the sample reflects good adherence by the Triage Nurse (IOA) to the current sampling protocol in place at the Emergency Department of Clermont-Ferrand University Hospital. In most cases, S100B testing in these patients was likely performed due to a lack of awareness of their anticoagulation status by the triage nurse at the time of admission. Nonetheless, the S100B result did not impact the quality of care, as a brain CT scan was systematically ordered by the treating physician regardless of the S100B result, including in S100B-negative cases. The physicians managing these patients demonstrated appropriate knowledge of the clinical guidelines concerning the use of S100B protein. Moreover, the small sample size is not necessarily a major concern in evaluating the diagnostic performance of S100B, given the strong reliability of this biomarker in the context of mild traumatic brain injury (mTBI). Second, our study was monocentric and conducted in a single hospital, which may limit the generalizability of the findings. However, it ensured consistency in patient management protocols for those presenting with anticoagulant-related head trauma. Finally, as this was a retrospective study, we can only propose hypotheses regarding the validity of S100B measurement in anticoagulated patients with mTBI. Nevertheless, to our knowledge, this is the second published study specifically focusing on the role of S100B protein in this growing patient population. The number of anticoagulated individuals continues to increase (39), particularly among the elderly, who are highly susceptible to falls\u0026mdash;a major public health concern affecting an estimated 26.5% of older adults worldwide (95% CI: 23.4\u0026ndash;29.8%).[34]\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eOur study is one of the first to evaluate the diagnostic value of serum S100B protein in elderly patients receiving anticoagulant therapy and admitted to the emergency department for mild traumatic brain injury. At the established threshold of 0.10 \u0026micro;g/L, S100B protein demonstrated excellent diagnostic accuracy for assessing the risk of intracranial bleeding, with a negative predictive value of 100% and an area under the curve (AUC) of 0.94.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u0026bull; mTBI: Mild Traumatic Brain Injury\u003c/p\u003e\n\u003cp\u003e\u0026bull; CT: Computed Tomography\u003c/p\u003e\n\u003cp\u003e\u0026bull;\u0026nbsp;OR: Odds Ratio\u003c/p\u003e\n\u003cp\u003e\u0026bull;\u0026nbsp;ED: Emergency Department\u003c/p\u003e\n\u003cp\u003e\u0026bull;\u0026nbsp;NPV: Negative Predictive Value\u003c/p\u003e\n\u003cp\u003e\u0026bull;\u0026nbsp;IQR: Interquartile Range\u003c/p\u003e\n\u003cp\u003e\u0026bull;\u0026nbsp;SD: Standard Deviation\u003c/p\u003e\n\u003cp\u003e\u0026bull;\u0026nbsp;DOAC: Direct Oral Anticoagulant\u003c/p\u003e\n\u003cp\u003e\u0026bull;\u0026nbsp;VKA: Vitamin K Antagonist\u003c/p\u003e\n\u003cp\u003e\u0026bull;\u0026nbsp;GCS: Glasgow Coma Scale\u003c/p\u003e\n\u003cp\u003e\u0026bull;\u0026nbsp;LMWH: Low Molecular Weight Heparin\u003c/p\u003e\n\u003cp\u003e\u0026bull;\u0026nbsp;ICH: Intracranial Hemorrhage\u003c/p\u003e\n\u003cp\u003e\u0026bull;\u0026nbsp;INR: International Normalized Ratio\u003c/p\u003e\n\u003cp\u003e\u0026bull;\u0026nbsp;WHO: World Health Organization\u003c/p\u003e\n\u003cp\u003e\u0026bull;\u0026nbsp;S100B: S100\u0026beta; Protein\u003c/p\u003e\n\u003cp\u003e\u0026bull;\u0026nbsp;TBI: Traumatic Brain Injury\u003c/p\u003e\n\u003cp\u003e\u0026bull;\u0026nbsp;AUC: Area Under the Curve\u003c/p\u003e\n\u003cp\u003e\u0026bull; PPV: Positive Predictive Value\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe RATED Registry\u0026nbsp;was approved by the institutional review board (CPP Sud-Est VI, IRB number: 00008526–2013/CE37) and was declared to the French Data Protection Authority and registered as a clinical trial (NCT02706080, Registered 01 September 2017).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed during this study are not publicly available but may be obtained from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFM \u0026nbsp;has served as a consultant for Bayer HealthCare Pharmaceuticals and Sanofi, been a speaker for Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim, Daiichi-Sankyo, Leo-pharma, Pfizer, Sanofi, and Abbott, and has received grants from Sanofi, Bayer HealthCare, and LFB\u003c/p\u003e\n\u003cp\u003eVS has served as consultant for Roche Diagnostics, Abbott Diagnostics, Biomérieux, Diasorin, and Snibe.\u003c/p\u003e\n\u003cp\u003eAuthors authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific funding from public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLO, FM: study design, data analysis and interpretation, data collection, manuscript drafting\u003c/p\u003e\n\u003cp\u003eDT: data interpretation, data collection, manuscript approval\u003c/p\u003e\n\u003cp\u003eSC: statistical analysis, data interpretation, manuscript approval\u003c/p\u003e\n\u003cp\u003eRD, DR: data collection, data interpretation, manuscript approval\u003c/p\u003e\n\u003cp\u003eJS, DB, VS: study design, data analysis and interpretation, manuscript approval\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors had full access to all the data (including statistical reports and tables) and take full responsibility for data integrity and accuracy. All authors critically revised and approved the final version of the manuscript submitted for publication.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMaas AIR, Menon DK, David Adelson PD, Andelic N, Bell MJ, Belli A, et al. Traumatic brain injury: Integrated approaches to improve prevention, clinical care, and research. Lancet Neurol. 2017;16:987\u0026ndash;1048. https://doi.org/10.1016/S1474-4422(17)30371-X\u003c/li\u003e\n\u003cli\u003eTagliaferri F, Compagnone C, Korsic M, Servadei F, Kraus J. A systematic review of brain injury epidemiology in Europe. Acta Neurochir (Wien). 2006;148:255\u0026ndash;67. https://doi.org/10.1007/s00701-005-0651-y\u003c/li\u003e\n\u003cli\u003eSpaniolas K, Cheng JD, Gestring ML, Sangosanya A, Stassen NA, Bankey PE. Ground level falls are associated with significant mortality in elderly patients. J Trauma - Inj Infect Crit Care. 2010;69:821\u0026ndash;4. https://doi.org/10.1097/TA.0b013e3181efc6c6\u003c/li\u003e\n\u003cli\u003eFu TS, Jing R, McFaull SR, Cusimano MD. Recent trends in hospitalization and in-hospital mortality associated with traumatic brain injury in Canada: A nationwide, population-based study. J Trauma Acute Care Surg. 2015;79:449\u0026ndash;54. https://doi.org/10.1097/ta.0000000000000733\u003c/li\u003e\n\u003cli\u003eXu Y, Holbrook AM, Simpson CS, Dowlatshahi D, Johnson AP. Prescribing patterns of novel oral anticoagulants following regulatory approval for atrial fibrillation in Ontario, Canada: a population-based descriptive analysis. CMAJ Open. Joule Inc.; 2013;1:E115\u0026ndash;9. https://doi.org/10.9778/cmajo.20130032\u003c/li\u003e\n\u003cli\u003eCipriano A, Park N, Pecori A, Bionda A, Bardini M, Frassi F, et al. Predictors of post-traumatic complication of mild brain injury in anticoagulated patients: DOACs are safer than VKAs. Intern Emerg Med. 2021;16:1061\u0026ndash;70. https://doi.org/10.1007/s11739-020-02576-w\u003c/li\u003e\n\u003cli\u003eMinhas H, Welsher A, Turcotte M, Eventov M, Mason S, Nishijima DK, et al. Incidence of intracranial bleeding in anticoagulated patients with minor head injury: a systematic review and meta-analysis of prospective studies. Br J Haematol. Blackwell Publishing Ltd; 2018;183:119\u0026ndash;26. https://doi.org/10.1111/bjh.15509\u003c/li\u003e\n\u003cli\u003eSardar P, Chatterjee S, Wu WC, Lichstein E, Ghosh J, Aikat S, et al. New Oral Anticoagulants Are Not Superior to Warfarin in Secondary Prevention of Stroke or Transient Ischemic Attacks, but Lower the Risk of Intracranial Bleeding: Insights from a Meta-Analysis and Indirect Treatment Comparisons. PLoS ONE. 2013;8. https://doi.org/10.1371/journal.pone.0077694\u003c/li\u003e\n\u003cli\u003eGil-Jardin\u0026eacute; C, Payen JF, Bernard R, Bobbia X, Bouzat P, Catoire P, et al. Management of patients suffering from mild traumatic brain injury 2023. Anaesth Crit Care Pain Med [Internet]. Anaesth Crit Care Pain Med; 2023 [cited 2024 Jan 30];42. https://doi.org/10.1016/J.ACCPM.2023.101260\u003c/li\u003e\n\u003cli\u003eEaster JS, Haukoos JS, Meehan WP, Novack V, Edlow JA. Will Neuroimaging Reveal a Severe Intracranial Injury in This Adult With Minor Head Trauma?: The Rational Clinical Examination Systematic Review. JAMA. American Medical Association; 2015;314:2672\u0026ndash;81. https://doi.org/10.1001/JAMA.2015.16316\u003c/li\u003e\n\u003cli\u003eStiell IG, Lesiuk H, Wells GA, McKnight RD, Brison R, Clement C, et al. The Canadian CT head rule study for patients with minor head injury: Rationale, objectives, and methodology for phase I (derivation). Ann Emerg Med. Mosby Inc.; 2001;38:160\u0026ndash;9. https://doi.org/10.1067/mem.2001.116796\u003c/li\u003e\n\u003cli\u003eUnd\u0026eacute;n J, Romner B. 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[Interest of S100B protein blood level determination for the management of patients with minor head trauma]. Ann Biol Clin Paris. 2009;67:425\u0026ndash;31. https://doi.org/10.1684/abc.2009.0347\u003c/li\u003e\n\u003cli\u003ePoislane P-A, Papin M, Masson D, Goffinet N, David A, Le Bastard Q, et al. Diagnostic performance of S100B assay for intracranial hemorrhage detection in patients with mild traumatic brain injury under antiplatelet or anticoagulant therapy. Sci Rep. 2025;15:5741. https://doi.org/10.1038/s41598-025-89927-9\u003c/li\u003e\n\u003cli\u003eBackus BE, Moustafa F, Skogen K, Sapin V, Rane N, Moya-Torrecilla F, et al. Consensus paper on the assessment of adult patients with traumatic brain injury with Glasgow Coma Scale 13\u0026ndash;15 at the emergency department: A multidisciplinary overview. Eur J Emerg Med. 2024;31:240\u0026ndash;9. https://doi.org/10.1097/MEJ.0000000000001140\u003c/li\u003e\n\u003cli\u003eUnd\u0026eacute;n J, Ingebrigtsen T, Romner B, Committee N. Scandinavian guidelines for initial management of minimal , mild and moderate head injuries in adults : an evidence and consensus-based update Scandinavian guidelines for initial management of minimal , mild and moderate head injuries in adults : an evide. BMC Med. BioMed Central Ltd; 2013;11:50. https://doi.org/10.1186/1741-7015-11-50\u003c/li\u003e\n\u003cli\u003eAlber B, Hein R, Grabe C, Caroli U, Luppa PB. Multicenter evaluation of the analytical and clinical performance of the Elecsys\u0026reg; S100 immunoassay in patients with malignant melanoma. Clin Chem Lab Med. 2005;43:557\u0026ndash;63. https://doi.org/10.1515/CCLM.2005.097\u003c/li\u003e\n\u003cli\u003eBiberthaler P, Linsenmeier U, Pfeifer KJ, Kroetz M, Mussack T, Kanz KG, et al. Serum S-100B concentration provides additional information for the indication of computed tomography in patients after minor head injury a prospective multicenter study. Shock. 2006;25:446\u0026ndash;53. https://doi.org/10.1097/01.shk.0000209534.61058.35\u003c/li\u003e\n\u003cli\u003eWania R, Lampart A, Niedermeier S, Stahl R, Trumm C, Reidler P, et al. Diagnostic value of protein S100b as predictor of traumatic intracranial haemorrhage in elderly adults with low-energy falls: results from a retrospective observational study. Eur J Trauma Emerg Surg Off Publ Eur Trauma Soc. 2024;50:205\u0026ndash;13. https://doi.org/10.1007/s00068-023-02324-7\u003c/li\u003e\n\u003cli\u003eAllouchery G, Moustafa F, Roubin J, Pereira B, Schmidt J, Raconnat J, et al. Clinical validation of S100B in the management of a mild traumatic brain injury: issues from an interventional cohort of 1449 adult patients. Clin Chem Lab Med. 2018;56:1897\u0026ndash;904. https://doi.org/10.1515/cclm-2018-0471\u003c/li\u003e\n\u003cli\u003eOris C, Bouillon-Minois J-B, Pinguet J, Kahouadji S, Durif J, Mesl\u0026eacute; V, et al. Predictive Performance of Blood S100B in the Management of Patients Over 65 Years Old With Mild Traumatic Brain Injury. J Gerontol A Biol Sci Med Sci. 2021;76:1471\u0026ndash;9. https://doi.org/10.1093/gerona/glab055\u003c/li\u003e\n\u003cli\u003ePoislane P-A, Papin M, Masson D, Goffinet N, David A, Le Bastard Q, et al. Diagnostic performance of S100B assay for intracranial hemorrhage detection in patients with mild traumatic brain injury under antiplatelet or anticoagulant therapy. Sci Rep. 2025;15:5741. https://doi.org/10.1038/s41598-025-89927-9\u003c/li\u003e\n\u003cli\u003eRiccardi A, Spinola B, Minuto P, Ghinatti M, Guiddo G, Malerba M, et al. Intracranial complications after minor head injury (MHI) in patients taking vitamin K antagonists (VKA) or direct oral anticoagulants (DOACs). Am J Emerg Med. Elsevier Inc; 2017;35:1317\u0026ndash;9. https://doi.org/10.1016/j.ajem.2017.03.072\u003c/li\u003e\n\u003cli\u003eTurcato G, Zannoni M, Zaboli A, Zorzi E, Ricci G, Pfeifer N, et al. Direct Oral Anticoagulant Treatment and Mild Traumatic Brain Injury: Risk of Early and Delayed Bleeding and the Severity of Injuries Compared with Vitamin K Antagonists. J Emerg Med. Elsevier USA; 2019;57:817\u0026ndash;24. https://doi.org/10.1016/j.jemermed.2019.09.007\u003c/li\u003e\n\u003cli\u003eTurcato G, Zaboli A, Zannoni M, Ricci G, Zorzi E, Ciccariello L, et al. Risk factors associated with intracranial bleeding and neurosurgery in patients with mild traumatic brain injury who are receiving direct oral anticoagulants. Am J Emerg Med. W.B. Saunders; 2021;43:180\u0026ndash;5. https://doi.org/10.1016/j.ajem.2020.02.046\u003c/li\u003e\n\u003cli\u003eCipriano A, Pecori A, Bionda AE, Bardini M, Frassi F, Leoli F, et al. Intracranial hemorrhage in anticoagulated patients with mild traumatic brain injury: significant differences between direct oral anticoagulants and vitamin K antagonists. Intern Emerg Med. Springer-Verlag Italia s.r.l.; 2018;13:1077\u0026ndash;87. https://doi.org/10.1007/S11739-018-1806-1/METRICS\u003c/li\u003e\n\u003cli\u003eSanting JAL, Hopman JH, Verheul RJ, van der Naalt J, van den Brand CL, Jellema K. Clinical value of S100B in detecting intracranial injury in elderly patients with mild traumatic brain injury. Injury. Elsevier; 2024;55:111313. https://doi.org/10.1016/J.INJURY.2024.111313\u003c/li\u003e\n\u003cli\u003eAlrajhi KN, Perry JJ, Forster AJ. Intracranial bleeds after minor and minimal head injury in patients on warfarin. J Emerg Med. Elsevier USA; 2015;48:137\u0026ndash;42. https://doi.org/10.1016/j.jemermed.2014.08.016\u003c/li\u003e\n\u003cli\u003eTesta L, Zoccai GB, Porto I, Trotta G, Agostoni P, Andreotti F, et al. Adjusted Indirect Meta-Analysis of Aspirin Plus Warfarin at International Normalized Ratios 2 to 3 Versus Aspirin Plus Clopidogrel After Acute Coronary Syndromes. Am J Cardiol. 2007;99:1637\u0026ndash;42. https://doi.org/10.1016/j.amjcard.2007.01.052\u003c/li\u003e\n\u003cli\u003eCosta G, Gon\u0026ccedil;alves L, Teixeira R. The efficacy and safety of direct oral anticoagulants plus aspirin in symptomatic lower extremity peripheral arterial disease: a systematic review and meta-analysis of randomized controlled trials. J Thromb Thrombolysis. J Thromb Thrombolysis; 2021;52:904\u0026ndash;13. https://doi.org/10.1007/S11239-021-02417-3\u003c/li\u003e\n\u003cli\u003eKaramian A, Farzaneh H, Khoshnoodi M, Maleki N, Karamian A, Stufflebeam S, et al. Diagnostic Accuracy of S100B in Predicting Intracranial Abnormalities on CT Imaging Following Mild Traumatic Brain Injury: A Systematic Review and Meta-analysis. Neurocrit Care. 2025;42:1025\u0026ndash;42. https://doi.org/10.1007/s12028-024-02189-7\u003c/li\u003e\n\u003cli\u003eSalari N, Darvishi N, Ahmadipanah M, Shohaimi S, Mohammadi M. Global prevalence of falls in the older adults: a comprehensive systematic review and meta-analysis. J Orthop Surg. BioMed Central Ltd; 2022;17. https://doi.org/10.1186/s13018-022-03222-1\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Mild Traumatic Brain Injury, S100B protein, anticoagulants, blood biomarkers","lastPublishedDoi":"10.21203/rs.3.rs-7793527/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7793527/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eMild traumatic brain injury (mTBI) is a common reason for emergency department visits. Its incidence is increasing, particularly among elderly individuals, who are often receiving anticoagulant therapy.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eThe aim of our study was to evaluate the diagnostic performance of serum S100B protein in anticoagulated patients admitted to the emergency department for mTBI.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eWe conducted a retrospective, single-center, observational study from January 1, 2014, to August 15, 2022, at the Emergency Department of Clermont-Ferrand University Hospital. We included all patients aged over 18 years who presented with mTBI, were on anticoagulant therapy, and underwent both S100B testing and a brain CT scan.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eAmong the 46 patients included, 8 (17.4%) had an S100B level\u0026thinsp;\u0026lt;\u0026thinsp;0.10 \u0026micro;g/L. Three patients (6.5%) experienced an intracranial hemorrhagic event; all had S100B levels\u0026thinsp;\u0026gt;\u0026thinsp;0.10 \u0026micro;g/L. At a threshold of 0.10 \u0026micro;g/L, S100B showed a sensitivity of 100% (95% CI: 29.2\u0026ndash;100), specificity of 93% (95% CI: 80.9\u0026ndash;98.5), positive predictive value of 50% (95% CI: 11.8\u0026ndash;88.2), and negative predictive value of 100% (95% CI: 91.2\u0026ndash;100). The area under the ROC curve was 0.94 (95% CI: 86.67\u0026ndash;100).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eS100B protein shows promising and robust diagnostic value for evaluating the risk of intracranial bleeding in anticoagulated patients with mTBI. Further prospective studies with larger sample sizes are needed to confirm this hypothesis.\u003c/p\u003e","manuscriptTitle":"Diagnostic Value of Serum S100B Protein in Anticoagulated Patients Admitted to the Emergency Department for Mild Traumatic Brain Injury","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-26 01:05:26","doi":"10.21203/rs.3.rs-7793527/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"36bbe6c7-86a4-4021-9221-058ba2a1df44","owner":[],"postedDate":"October 26th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-26T09:26:29+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-26 01:05:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7793527","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7793527","identity":"rs-7793527","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}