Variable Rate of D-dimer Predicts Venous Thromboembolism in Postoperative Fracture Patients: A Single-Center Retrospective Cohort Study

Variable Rate of D-dimer Predicts Venous Thromboembolism in Postoperative Fracture Patients: A Single-Center Retrospective Cohort Study | 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 Variable Rate of D-dimer Predicts Venous Thromboembolism in Postoperative Fracture Patients: A Single-Center Retrospective Cohort Study Xin-Miao Chen, Hui Huang, Fen-Hua Jin, Hui-Ying Li, Sheng-Qiao Shi, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7878480/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 The correlation between plasma D-dimer levels and deep vein thrombosis (DVT) remains inconsistent across studies. This study aimed to investigate whether the variable rate of D-dimer is a more accurate predictor of venous thromboembolism (VTE) compared to D-dimer alone. Methods Demographic data, fracture classification, and D-dimer levels were collected. The variable rate of D-dimer was defined as the ratio of postoperative D-dimer to preoperative D-dimer. Duplex ultrasonography was used to evaluate DVT in the lower extremities, while computed tomography pulmonary angiography was conducted for patients suspected of having pulmonary thromboembolism (PTE). Results A total of 77,609 traumatic fracture patients without VTE (mean age: 51.36 ± 28.72 years) and 2,813 patients with VTE (mean age: 68.13 ± 26.65 years) were included. Among the VTE patients, 36 had upper limb fractures, 522 had spine fractures, 269 had pelvic fractures, 1,265 had lower extremity fractures, and 721 had compound or other types of fractures. Of these, 2,743 patients developed lower extremity venous thromboembolism, and 70 suffered from PTE. The variable rate of D-dimer was significantly higher in postoperative traumatic fracture patients with VTE (2.79 ± 1.77) compared to preoperative patients without VTE (1.35 ± 0.70). Using a cutoff point of 2.0 for the variable rate of D-dimer, sensitivity and specificity were 83.44% and 88.60%, respectively. Multivariate analysis revealed that age > 60 years, female sex, and lower extremity fractures were independent risk factors for VTE. Conclusions The variable rate of D-dimer is strongly correlated with VTE in postoperative traumatic fracture patients. It serves as a useful predictor of VTE, particularly in elderly patients, females, and those with lower extremity fractures. D-dimer Variable rate of D-dimer Traumatic fracture Venous thromboembolism Pulmonary embolism Figures Figure 1 Introduction Venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE), is a multifactorial condition arising from the interaction between acquired or inherited thrombophilic predispositions and transient clinical risk factors [ 1 ]. Patients undergoing orthopedic surgery are at increased risk of VTE, with reported incidence rates ranging from 6% to 61%, influenced by patient demographics, study duration, diagnostic methods, and the use of thromboprophylaxis [ 3 , 4 ]. Plasma D-dimer levels reflect fibrin formation and degradation, serving as a biomarker of active coagulation and fibrinolysis. Although a conventional threshold of 500 ng/mL is widely used in clinical practice, elevated D-dimer levels lack specificity for VTE and may also be observed in various non-thrombotic conditions, including traumatic fractures, malignancy, recent surgery, trauma, and infection [ 5 , 6 ]. Consequently, the utility of D-dimer as a standalone predictor of VTE remains limited. For early detection of VTE, identifying high-risk individuals through clinically relevant risk factors or laboratory biomarkers is both feasible and clinically meaningful. Substantial efforts have been made in orthopedics and other surgical disciplines to refine risk stratification, such as implementing age-adjusted D-dimer cutoffs to improve specificity and guide decision-making in patients with suspected VTE [ 7 ]. However, neither standard nor age-adjusted D-dimer thresholds have been adequately validated for predicting postoperative VTE in patients with traumatic fractures. Moreover, no established biomarker is currently recommended for assessing VTE risk or enhancing predictive accuracy in this population. Given these limitations, there is a pressing need to identify a reliable clinical indicator that can complement or surpass the performance of D-dimer in VTE prediction. Emerging evidence suggests that dynamic monitoring of D-dimer levels may enhance early detection of VTE [ 8 , 9 ]. Based on these findings, we hypothesized that the D-dimer variability rate—defined as the ratio of postoperative to preoperative D-dimer levels—may provide superior predictive value compared to absolute D-dimer concentrations alone. Our retrospective study demonstrates that the D-dimer variability rate serves as a novel and potentially robust predictor of VTE in patients with traumatic fractures following orthopedic surgery. Materials and Methods Patients and Methods This retrospective study was conducted at The Second Affiliated Hospital of Wenzhou Medical University in Wenzhou, China. A total of 80,422 patients with traumatic fractures (46,903 males and 33,519 females; mean age: 61.03 ± 25.19 years) were enrolled between January 2020 and June 2025. Inclusion criteria were: (1) diagnosis of lower extremity, pelvic, spinal, craniofacial, or multiple compound fractures; and (2) age ≥ 18 years. Exclusion criteria included: (1) pathological fractures; (2) pre-injury anticoagulation therapy; (3) prior history of venous thromboembolism; (4) active malignancy; (5) pregnancy; (6) acute systemic infection; (7) hepatic failure; and (8) coagulopathy or other blood disorders. Clinical characteristics of patients with and without VTE are summarized in Table 1 . Table 1 Demographic data Factors Traumatic fracture with VTE (n = 2813) Traumatic fracture without VTE (n = 77609) P Value DVT 2743 Preoperation stage Day 1–3 after operation Day 4–7 after operation Day > 8 after operation 323 655 1122 643 PTE 70 Gender < 0.01 Male 1180 45723 Female 1633 31886 No comorbidity 2293 65963 0.15 Comorbidity 520 11646 Hypertension 219 5615 0.32 Diabetes 95 2306 0.25 Coronary heart disease 33 336 0.23 Others with 2 diseases at least 173 3389 < 0.01 Types of traumatic fracture 77609 Upper limb 3 9977 1.00 Spine 422 9575 0.22 Pelvis 149 3480 0.06 Lower extremity 1485 39286 < 0.01 Compound fracture and others 721 15291 < 0.01 Surgical options 0.16 ORIF 2280 60503 CRIF 603 17106 D-dimer 5.26 ± 2.96 7.16 ± 5.19 < 0.01 Variable rate of D-dimer 1.35 ± 0.70 2.79 ± 1.77 < 0.01 Abbreviations: VTE, venous thromboembolism; PTE, pulmonary thromboembolism; ORIF, open reduction and internal fixation; CRIF, closed reduction and internal fixation. Plasma D-dimer Determination Plasma D-dimer levels were measured using a D-dimer assay kit (Dade Behring Co.) on the Sysmex CA-1500 automated coagulation analyzer employing the immunoturbidimetric method. Measurements were performed preoperatively (day 1) and postoperatively on days 1, 3, and 7. The variable rate of D-dimer was calculated as the ratio of postoperative to preoperative D-dimer levels. Diagnosis of DVT or PE All trauma patients underwent routine screening for deep vein thrombosis using duplex ultrasonography. Computed tomography pulmonary angiography (CTPA) was performed in patients with clinical suspicion of PTE. Statistical Analysis Data were analyzed using SigmaPlot version 13.0. Categorical variables are presented as frequencies and proportions, while continuous variables are expressed as mean ± standard deviation. Comparisons between groups were performed using the chi-square test or Fisher’s exact test for categorical data, and Student’s t-test or Wilcoxon rank-sum test for continuous variables, as appropriate. Multiple logistic regression analysis was conducted to identify independent risk factors for VTE in this patient cohort. Receiver operating characteristic (ROC) curve analysis was used to determine optimal cut-off values for the D-dimer variable rate, with the threshold selected based on the maximum Youden index. A two-sided p-value < 0.05 was considered statistically significant. Results Demographic Data The mean age of traumatic fracture patients without VTE was 51.36 ± 28.72 years, which was significantly lower than that of patients with VTE (68.13 ± 26.65 years). Among patients with VTE, fracture distribution included 269 pelvic fractures, 522 spinal fractures, 336 upper limb or craniofacial bone fractures, 1,265 lower extremity fractures, and 421 complex fractures. Distribution of VTE Patients and D-dimer Variability in Traumatic Fracture A total of 323 patients were diagnosed with VTE preoperatively, 755 during postoperative days 1–3, 1,292 between days 4–7, and 443 after day 8, indicating a peak incidence in the early postoperative period. As shown in Table 1 , D-dimer levels in non-VTE patients were 5.56 ± 3.08 mg/L preoperatively and 7.15 ± 5.18 mg/L postoperatively. In contrast, VTE patients exhibited D-dimer levels of 5.25 ± 2.96 mg/L preoperatively and 11.98 ± 5.54 mg/L postoperatively. Notably, the the variable rate of D-dimer was markedly elevated in postoperative VTE patients (2.79 ± 1.77) compared to preoperative non-VTE patients (1.35 ± 0.70), with a statistically significant difference ( P < 0.001). Risk Factors for Postoperative VTE in Traumatic Fracture Patients No significant association was found between the D-dimer variability rate and comorbidities such as hypertension, diabetes, or coronary heart disease in either the VTE or non-VTE groups. Age and gender distributions were compared using the Student’s t-test and chi-square test, respectively, revealing statistically significant differences between the two groups (P < 0.05). The D-dimer variability rate was higher in elderly patients than in younger individuals. Furthermore, the incidence of VTE was significantly greater among patients with pelvic or lower extremity fractures compared to those with other fracture types. Female patients also demonstrated a higher prevalence of VTE relative to male patients. In univariate analysis, variables with P > 0.05 were excluded, and the remaining factors were entered into multivariate logistic regression analysis. Age, D-dimer variability rate, and gender were identified as significant independent predictors of postoperative VTE. Results from both univariate and multivariate analyses are summarized in Table 2 . Table 2 Multiple logistic regression analysis for traumatic fracture patients with or without VTE Risk factors Odds ratio 95% CI P -value Age > 60 1.28 1.24–1.32 < 0.01 Female 1.96 1.38–8.93 < 0.01 Upper limb and or craniofacial bone 1.03 1.00-1.09 0.29 Spinal fracture 1.21 0.77–3.01 0.41 Pelvis 1.19 0.66–3.06 0.51 Lower extremity fracture 1.78 1.03–4.89 0.04 Compound fracture 1.36 0.97–2.55 0.09 Variable rate of D-dimer 1.74 0.94–2.08 < 0.01 Abbreviations: CI, confidence interval. Receiver operating characteristic (ROC) curve analysis indicated that the D-dimer variability rate exhibited superior diagnostic performance compared to absolute D-dimer levels for detecting VTE in traumatic fracture patients. The area under the ROC curve (AUC) for the D-dimer variability rate was 0.82 (95% CI: 0.79–0.84, P < 0.01). The optimal cutoff value, determined by maximizing the Youden index, was 2.0, yielding a sensitivity of 83.44% and a specificity of 88.60%. The odds ratio (OR) for the D-dimer variability rate was 1.74, confirming its role as an independent risk factor for postoperative VTE. The peak incidence of VTE occurred between postoperative days 3 and 7. Discussion VTE is a potentially life-threatening complication following traumatic injury. Elevated D-dimer levels are commonly observed in patients with traumatic fractures and are associated with an increased risk of VTE or PTE. However, D-dimer lacks specificity for the diagnosis of DVT and/or PTE. To the best of our knowledge, no previous studies have evaluated the variable rate of D-dimer as a predictor of VTE in postoperative orthopedic trauma patients. In this retrospective case-control study, we demonstrate that the variable rate of D-dimer has superior predictive value for VTE compared to absolute D-dimer levels alone. Numerous studies have established that patients with traumatic fractures are at significantly increased risk of developing VTE [ 10 ]. Moreover, VTE remains a leading cause of morbidity and mortality among post-traumatic patients undergoing orthopedic surgery [ 11 , 12 ]. Traumatic fractures are associated with elevated D-dimer concentrations and a pronounced increase in VTE incidence [ 13 ]. Plasma D-dimer levels rise systematically after surgery, and significant differences have been observed between patients with and without VTE [ 14 ]. Hansen ES et al. reported that elevated plasma D-dimer levels correlate with a higher risk of incidental VTE [15]. Furthermore, the modified IMPROVE VTE score, when combined with elevated D-dimer, identified a nearly threefold increase in VTE risk among medically ill patients [ 16 ]. Our study confirms that D-dimer levels are elevated in traumatic fracture patients; however, not all such patients develop VTE complications. The utility of D-dimer as a diagnostic marker for VTE is limited. While it exhibits high negative predictive value for ruling out VTE, its positive predictive value is poor due to low specificity [ 17 ]. Notably, our findings indicate that the variable rate of D-dimer—defined as the ratio of postoperative to preoperative D-dimer—is more strongly correlated with VTE than D-dimer alone. Additionally, ROC analysis revealed a significantly greater discriminatory capacity for the variable rate of D-dimer in predicting postoperative VTE, whereas absolute D-dimer levels showed limited diagnostic accuracy. The optimal cutoff value for the variable rate of D-dimer was determined to be 2.0 after injury. These results suggest that monitoring the variable rate of D-dimer following trauma may improve VTE detection. Therefore, ultrasonography duplex and/or CTPA should be routinely considered in traumatic fracture patients when the variable rate of D-dimer exceeds 2.0. Importantly, our data also show that the peak incidence of VTE occurs between postoperative days 3 and 7. The association between age and VTE in fracture patients remains controversial. Some studies report that advanced age is an independent risk factor for thrombosis in adult trauma patients [ 18 , 19 ]. Conversely, Lapner et al. found no significant relationship between age and VTE incidence [ 20 ]. Despite these discrepancies, older age is generally recognized as a contributing factor to VTE development and is closely linked to age-adjusted D-dimer levels [ 21 ]. In our cohort, the incidence of VTE was significantly higher in elderly patients (age > 60 years) compared to younger individuals (age < 60 years). Multivariate logistic regression analysis confirmed that age is an independent risk factor for VTE in traumatic fracture patients over 60 years of age. Furthermore, the variable rate of D-dimer was markedly higher in elderly patients with VTE than in younger patients without VTE. Interestingly, however, we observed no significant increase in the variable rate of D-dimer in patients over 60 years of age regardless of VTE status, compared to those under 60. This suggests that, unlike conventional age-adjusted D-dimer thresholds, the variable rate of D-dimer does not appear to be influenced by age and may serve as a non-age-dependent screening tool for VTE in traumatic fracture patients. Gender is another debated independent risk factor for VTE [ 22 – 25 ]. Berndtson et al. found no difference in VTE incidence between male and female trauma patients, even after adjusting for menopausal status [ 26 ]. In contrast, Arnesen et al. suggested that men may have a higher intrinsic risk of VTE than women across all age groups [ 27 ]. Nevertheless, most epidemiological studies report a 2- to 3-fold higher incidence of first-time VTE in women during their reproductive years compared to age-matched men [ 28 , 29 ]. In our retrospective analysis, female traumatic fracture patients exhibited a higher risk of VTE than their male counterparts. Multivariate analysis further confirmed female sex as an independent predictor of VTE in this population. Notably, among female patients, the incidence of VTE was higher in postmenopausal women than in premenopausal women, which aligns with findings from Beyer-Westendorf et al. [ 30 ]. Data from the COMMAND VTE Registry indicate that the use of sex hormones, including combined oral contraceptives or hormone replacement therapy, substantially increases the risk of VTE, particularly in patients with an elevated intrinsic predisposition for thromboembolic complications [ 30 ]. Importantly, three large studies—the MEGA study, the Hokusai-VTE study, and the RIETE registry—have consistently demonstrated sex-related differences in the anatomical presentation of VTE, with PTE more frequently presenting as the initial manifestation in women compared to men [ 31 ]. Differences in D-dimer levels between males and females are diagnosis-dependent. However, no significant difference has been reported in the optimal D-dimer cutoff values for excluding PTE or DVT between the two sexes [ 22 , 25 ]. Notably, our retrospective analysis revealed that the variable rate of D-dimer was significantly higher in female traumatic fracture patients with VTE compared to those without VTE, which may partially explain the increased incidence of VTE observed in female fracture patients. In summary, age and sex are independent risk factors for VTE in traumatic fracture patients. Advanced age and female sex are associated with a higher variable rate of D-dimer. The variable rate of D-dimer appears to be a more effective diagnostic indicator for VTE than absolute D-dimer levels alone. Further studies are needed to validate the clinical utility of measuring the variable rate of D-dimer in this population. Abbreviations DVT deep vein thrombosis VTE venous thromboembolism PTE pulmonary thromboembolism CTPA computed tomography pulmonary angiography ROC receiver operating characteristic AUC area under the ROC curve OR odds ratio Declarations Ethics approval and consent to participate This retrospective study was performed in accordance with the Declaration of Helsinki and the study protocol was approved by ethical standards of the Institutional Review Board of Ethics Committee of The Second Affiliated Hospital of Wenzhou medical University. Informed consent was obtained from each participant. Consent for publication Not applicable. Data Availability The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Availability of data and materials We have no research data outside the submitted manuscript file. Competing Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Funding The author(s) received no financial support for the research, authorship, and/or publication of this article. Authors' contributions Conceptualization was led by X.-M.C. and X.-D.X. The methodology was designed by X.-M.C. and S.-Q.S. Data collection and investigation were performed by H.H., F.-H.J., and H.-Y.L. Formal analysis was conducted by X.-M.C. The original draft was written by X.-M.C. The manuscript was reviewed and edited by S.-Q.S. and X.-D.X. Supervision and project administration were the responsibility of X.-D.X. Acknowledgements None declared. References Heit JA, Spencer FA, White RH. The epidemiology of venous thromboembolism. J Thromb Thrombolysis. 2016.;41(1):3–14. Kahn SR, Shivakumar S. What's new in VTE risk and prevention in orthopedic surgery. Res Pract Thromb Haemost. 2020;4(3):366–376. Crous-Bou M, Harrington LB, Kabrhel C. Environmental and Genetic Risk Factors Associated with Venous Thromboembolism. Semin Thromb Hemost. 2016;42(8):808–820. Fisher W. Managing hip fracture and lower limb surgery in the emergency setting: Potential role of non-vitamin K antagonist oral anticoagulants. J Trauma Acute Care Surg. 2017;82(6):1112–1121. Linkins LA, Takach Lapner S. Review of D-dimer testing: Good, Bad, and Ugly. Int J Lab Hematol. 2017;39 Suppl 1:98–103. Singer AJ, Zheng H, Francis S, Fermann GJ, Chang AM, Parry BA, Giordano N, Kabrhel C. D-dimer levels in VTE patients with distal and proximal clots. Am J Emerg Med. 2019;37(1):33–37. Riva N, Righini M, Camporese G, Iotti M, Bucherini E, Kamphuisen PW, Verhamme P, Douketis JD, Tonello C, Prandoni P, Ageno W, PALLADIO Study Investigators. Accuracy of age-adjusted D-dimer to rule out deep vein thrombosis in the elderly. Thromb Res. 2019;174:148–150. Riva N, Camporese G, Iotti M, Bucherini E, Righini M, Kamphuisen PW, Verhamme P, Douketis J D, Tonello C, Prandoni P, Ageno W, PALLADIO Study Investigators. Age-adjusted D-dimer to rule out deep vein thrombosis: findings from the PALLADIO algorithm. J Thromb Haemost. 2018;16:271–278. Johnson ED, Schell JC, Rodgers GM. The D-dimer assay. Am J Hematol. 2019;94(7):833–839. MacDonald DRW, Neilly D, Schneider PS, Bzovsky S, Sprague S, Axelrod D, Poolman RW, Frihagen F, Bhandari M, Swiontkowski M, Schemitsch EH, Stevenson IM; FAITH Investigators; HEALTH Investigators. Venous Thromboembolism in Hip Fracture Patients: A Subanalysis of the FAITH and HEALTH Trials. J Orthop Trauma. 2020;34 Suppl 3:S70-S75. Yoon JY, Kim S, Chang JS, Yoon PW, Kim JW. Venous thromboembolism after delayed surgery for a hip fracture: A retrospective cohort study. Geriatr Gerontol Int. 2020;20(12):1151–1156 Flevas DA, Megaloikonomos PD, Dimopoulos L, Mitsiokapa E, Koulouvaris P, Mavrogenis AF. Thromboembolism prophylaxis in orthopaedics: an update. EFORT Open Rev. 2018;3(4):136–148. Whiting PS, Jahangir AA. Thromboembolic Disease After Orthopedic Trauma. Orthop Clin North Am. 2016;47(2):335–344. Yang Y, Zan P, Gong J, Cai M. d-Dimer as a Screening Marker for Venous Thromboembolism After Surgery Among Patients Younger Than 50 With Lower Limb Fractures. Clin Appl Thromb Hemost. 2017;23(1):78–83. 5 Hansen ES, Rinde FB, Edvardsen MS, Hindberg K, Latysheva N, Aukrust P, Ueland T, Michelsen AE, Hansen JB, Brækkan SK, Morelli VM. Elevated plasma D-dimer levels are associated with risk of future incident venous thromboembolism. Thromb Res. 2021;208:121–126. Spyropoulos AC, Lipardi C, Xu J, Peluso C, Spiro TE, De Sanctis Y, Barnathan ES, Raskob GE. Modified IMPROVE VTE Risk Score and Elevated D-Dimer Identify a High Venous Thromboembolism Risk in Acutely Ill Medical Population for Extended Thromboprophylaxis. TH Open. 2020;4(1):e59-e65. Niikura T, Sakai Y, Lee SY, Iwakura T, Nishida K, Kuroda R, Kurosaka M. D-dimer levels to screen for venous thromboembolism in patients with fractures caused by high-energy injuries. J Orthop Sci. 2015;20(4):682–688. Huang CH, Wang WH, Kor CT, Hsiao CH, Chang CC. Risk of venous thromboembolism in elderly patients with vertebral compression fracture: A population-based case-control study. Medicine (Baltimore). 2020;99(18):e20072. Nastasi AJ, Canner JK, Lau BD, Streiff MB, Aboagye JK, Kraus PS, Hobson DB, Van Arendonk KJ, Haut ER. Characterizing the relationship between age and venous thromboembolism in adult trauma patients: findings from the National Trauma Data Bank and the National Inpatient Sample. J Surg Res. 2017;216:115–122. Takach Lapner S, Julian JA, Linkins L-A, Bates SM, Kearon C. Questioning the use of an age-adjusted D-dimer threshold to exclude venous thromboembolism: analysis of individual patient data from two diagnostic studies. J Thromb Haemost 2016; 14(10): 1953–1959. Haase C, Joergensen M, Ellervik C, Joergensen MK, Bathum L. Age- and sex-dependent reference intervals for D-dimer: evidence for a marked increase by age. Thromb Res. 2013;132(6):676–680. Reagh JJ, Zheng H, Stolz U, Parry BA, Chang AM, House SL, Giordano NJ, Cohen J, Singer AJ, Francis S, Prochaska JH, Zeserson E, Wild PS, Limkakeng AT Jr, Walters EL, LoVecchio F, Theodoro D, Hollander JE, Kabrhel C, Fermann GJ. Sex-related differences in D-dimer levels for venous thromboembolism screening. Acad Emerg Med. 2021;28(8):873–881. Legnani C, Cini M, Cosmi B, Carraro P, Tripodi A, Erba N, Palareti G. Age and gender specific cut-off values to improve the performance of D-dimer assays to predict the risk of venous thromboembolism recurrence. Intern Emerg Med. 2013;8(3):229–236. Giustozzi M, Valerio L, Agnelli G, Becattini C, Fronk EM, Klok FA, Konstantinides SV, Vedovati MC, Cohen AT, Barco S. Sex-specific differences in the presentation, clinical course, and quality of life of patients with acute venous thromboembolism according to baseline risk factors. Insights from the PREFER in VTE. Eur J Intern Med. 2021;88:43–51. Yoshikawa Y, Yamashita Y, Morimoto T, Amano H, Takase T, Hiramori S, Kim K, Oi M, Akao M, Kobayashi Y, Toyofuku M, Izumi T, Tada T, Chen PM, Murata K, Tsuyuki Y, Saga S, Sasa T, Sakamoto J, Kinoshita M, Togi K, Mabuchi H, Takabayashi K, Shiomi H, Kato T, Makiyama T, Ono K, Kimura T; COMMAND VTE Registry Investigators. Sex Differences in Clinical Characteristics and Outcomes of Patients With Venous Thromboembolism-From the COMMAND VTE Registry. Circ J. 2019;83(7):1581–1589. Berndtson AE, Costantini TW, Smith AM, Kobayashi L, Coimbra R.Does sex matter? Effects on venous thromboembolism risk in screened trauma patients. J Trauma Acute Care Surg. 2016;81(3):493–499. Arnesen CAL, Veres K, Horváth-Puhó E, Hansen J-B, Sørensen HT, Brækkan SK. Estimated lifetime risk of venous thromboembolism in men and women in a Danish nationwide cohort: impact of competing risk of death. Eur J Epidemiol. 2022; 37(2): 195–203. Sex-specific aspects of venous thromboembolism: What is new and what is next? Scheres LJJ, van Hylckama Vlieg A, Cannegieter SC. Res Pract Thromb Haemost. 2022;6(4):e12722. Marshall AL, Bartley AC, Ashrani AA, Pruthi RK, Durani U, Gonsalves WI, Kapoor P, Hashmi SK, Siddiqui MA, Go RS. Sex-based disparities in venous thromboembolism outcomes: A National Inpatient Sample (NIS)-based analysis. Vasc Med. 2017;22(2):121–127. Beyer-Westendorf J, Bauersachs R, Hach-Wunderle V, Zotz RB, Rott H. Sex hormones and venous thromboembolism - from contraception to hormone replacement therapy. Vasa. 2018;47(6):441–450. Scheres LJJ, Brekelmans MPA, Beenen LFM, Büller HR, Cannegieter SC, Middeldorp S. Sex-specific differences in the presenting location of a first venous thromboembolism. J Thromb Haemost. 2017;15(7):1344–1350. Additional Declarations No competing interests reported. Supplementary Files 20200112.xlsx 20200112.xlsx 20210112.xlsx 20210112.xlsx 20220112.xlsx 20220112.xlsx 20230112.xlsx 20230112.xlsx 20240112.xlsx 20240112.xlsx 20250106.xlsx 20250106.xlsx StatisticalAnalysis.xlsx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7878480","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":556565887,"identity":"de14f4f4-9770-4af5-8133-b1adcc7203eb","order_by":0,"name":"Xin-Miao Chen","email":"","orcid":"","institution":"Yuying Children's Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xin-Miao","middleName":"","lastName":"Chen","suffix":""},{"id":556565888,"identity":"c7610c34-7f61-47af-80eb-73cfa156ddcf","order_by":1,"name":"Hui Huang","email":"","orcid":"","institution":"Yuying Children's Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hui","middleName":"","lastName":"Huang","suffix":""},{"id":556565891,"identity":"6e7cd072-d76a-4ac5-9fd5-32c83e98166d","order_by":2,"name":"Fen-Hua Jin","email":"","orcid":"","institution":"Yuying Children's Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Fen-Hua","middleName":"","lastName":"Jin","suffix":""},{"id":556565892,"identity":"b14b20db-98ff-456d-bfc2-2af3a607f5ab","order_by":3,"name":"Hui-Ying Li","email":"","orcid":"","institution":"Yuying Children's Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hui-Ying","middleName":"","lastName":"Li","suffix":""},{"id":556565893,"identity":"930f76fc-ebaa-4915-a62e-1a181d4da70a","order_by":4,"name":"Sheng-Qiao Shi","email":"","orcid":"","institution":"Yuying Children's Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Sheng-Qiao","middleName":"","lastName":"Shi","suffix":""},{"id":556565894,"identity":"d80334be-9742-43e8-ad5d-a02d2d2ad2d1","order_by":5,"name":"Xiao-Dong Xia","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAklEQVRIiWNgGAWjYDACZhBhACISgLjiAFjwwAPitZw5wMAD0pJAnH1AZYxtEC0M+LQYHGd+wMxTYCfHwJ587OHXeXfk7MUOPwTaYien24Bdi2QzmwHjDINkYwaeZ+nGstueGfNIpxkAtSQbmx3AroWfGeiRDwbMiQ0SOWbSktsOJ/ZIJ4C0HEjchkMLGzP7B4YEg3qoljkgLekf8GrhZ+YB2XIYrEXyYwNISw5+WySbeQqAfjkO8kuaNMOxw8Y8t3MKDiQY4PaLwfnjG5h5/lSDQ0zyR81hOfbZ6Zs/fKiwk8OlBQjYf4BIe6ACZh6EUTiVowLGH0QqHAWjYBSMgpEFAHBrWRF/dYCZAAAAAElFTkSuQmCC","orcid":"","institution":"Yuying Children's Hospital of Wenzhou Medical University","correspondingAuthor":true,"prefix":"","firstName":"Xiao-Dong","middleName":"","lastName":"Xia","suffix":""}],"badges":[],"createdAt":"2025-10-16 13:54:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7878480/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7878480/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":97745133,"identity":"7843bef2-371d-49a4-9f55-eb6a81c2a74e","added_by":"auto","created_at":"2025-12-09 00:23:43","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":38702,"visible":true,"origin":"","legend":"","description":"","filename":"2025.10.13VRDdimer.docx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/47543994701d8cf31bf9158b.docx"},{"id":97745136,"identity":"7e692d62-9881-43f0-8596-f702cfd57bc1","added_by":"auto","created_at":"2025-12-09 00:23:43","extension":"tif","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":23128,"visible":true,"origin":"","legend":"","description":"","filename":"figure1.tif","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/5a56727faebee39ff9de7eba.tif"},{"id":97897077,"identity":"a16dfb21-b056-44da-931d-d772bb7ca791","added_by":"auto","created_at":"2025-12-10 15:37:25","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":21481,"visible":true,"origin":"","legend":"","description":"","filename":"table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/453156723abafd8d6dcb8819.docx"},{"id":97745138,"identity":"3ab37014-7ef4-49cc-8891-e10c9c24ed7e","added_by":"auto","created_at":"2025-12-09 00:23:43","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":19193,"visible":true,"origin":"","legend":"","description":"","filename":"table2.docx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/298d06a2acc4366adc54f932.docx"},{"id":97745139,"identity":"b5cfb2a4-8d38-43ff-a4fc-05dc0c018feb","added_by":"auto","created_at":"2025-12-09 00:23:43","extension":"json","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":7784,"visible":true,"origin":"","legend":"","description":"","filename":"5dafd540a29f49fda37dac8686294d77.json","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/2e07fb53c85fee2a4bc1b9b1.json"},{"id":97894543,"identity":"748ec7c6-4034-4a8f-980b-6937e3814ac9","added_by":"auto","created_at":"2025-12-10 15:32:41","extension":"xlsx","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":38508,"visible":true,"origin":"","legend":"","description":"","filename":"20200112.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/f24db72f34ed8b745922f069.xlsx"},{"id":97745158,"identity":"b039b8ec-5439-45d9-9ce2-1bb3e47cca8e","added_by":"auto","created_at":"2025-12-09 00:23:44","extension":"xlsx","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1541372,"visible":true,"origin":"","legend":"","description":"","filename":"20200112.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/17c800bcc56b91e0dd2bd317.xlsx"},{"id":97745142,"identity":"576cdd20-675e-4cc6-8c4c-6cd0c8edc2b1","added_by":"auto","created_at":"2025-12-09 00:23:43","extension":"xlsx","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":65566,"visible":true,"origin":"","legend":"","description":"","filename":"20210112.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/ef4f2c7a513d7de76c47b431.xlsx"},{"id":97896899,"identity":"501e4474-3d06-4aca-a4a6-ff4dec21a2ec","added_by":"auto","created_at":"2025-12-10 15:37:11","extension":"xlsx","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1651257,"visible":true,"origin":"","legend":"","description":"","filename":"20210112.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/e590b017e5c7a45040f015dc.xlsx"},{"id":97896953,"identity":"039195c0-6306-49b6-ad3b-6d51993e4b07","added_by":"auto","created_at":"2025-12-10 15:37:16","extension":"xlsx","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":100650,"visible":true,"origin":"","legend":"","description":"","filename":"20220112.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/58d76bd4a9aed8bd97395ba5.xlsx"},{"id":97745151,"identity":"c6fe9647-95ed-4f02-b539-c3f0bdcc5e02","added_by":"auto","created_at":"2025-12-09 00:23:44","extension":"xlsx","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1893362,"visible":true,"origin":"","legend":"","description":"","filename":"20220112.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/f149a0274026d5194a978ee4.xlsx"},{"id":97745165,"identity":"c9cd5d76-a6be-4d07-b86d-64ad61929d1d","added_by":"auto","created_at":"2025-12-09 00:23:44","extension":"xlsx","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":141120,"visible":true,"origin":"","legend":"","description":"","filename":"20230112.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/aa9cf04613edd3202c3d1d55.xlsx"},{"id":97896312,"identity":"bb9bce41-8c81-4627-b879-b9d4fcb02f34","added_by":"auto","created_at":"2025-12-10 15:36:19","extension":"xlsx","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2160004,"visible":true,"origin":"","legend":"","description":"","filename":"20230112.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/e27c860bd5753dacbb1e6018.xlsx"},{"id":97745156,"identity":"4c94f2fb-de77-4dd7-92bc-9e7e798743e9","added_by":"auto","created_at":"2025-12-09 00:23:44","extension":"xlsx","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":124621,"visible":true,"origin":"","legend":"","description":"","filename":"20240112.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/c287afaa449050f1c30cf432.xlsx"},{"id":97745157,"identity":"d9542aa2-528c-478b-8706-615de82dc995","added_by":"auto","created_at":"2025-12-09 00:23:44","extension":"xlsx","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2253629,"visible":true,"origin":"","legend":"","description":"","filename":"20240112.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/1ff9a952691f53bc0b27078b.xlsx"},{"id":97745166,"identity":"69b86102-0fb2-451e-a372-a65b8aec80ca","added_by":"auto","created_at":"2025-12-09 00:23:44","extension":"xlsx","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":78385,"visible":true,"origin":"","legend":"","description":"","filename":"20250106.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/88b53b52fd3c3ccd081461fa.xlsx"},{"id":97896328,"identity":"8b7ff49a-b244-4d80-9160-90ce96a729d6","added_by":"auto","created_at":"2025-12-10 15:36:21","extension":"xlsx","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1305740,"visible":true,"origin":"","legend":"","description":"","filename":"20250106.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/46d689d55ddf9b1a8d41ca4a.xlsx"},{"id":97745161,"identity":"e4799505-0583-4218-9d43-03206d20fa45","added_by":"auto","created_at":"2025-12-09 00:23:44","extension":"xlsx","order_by":17,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":170781,"visible":true,"origin":"","legend":"","description":"","filename":"StatisticalAnalysis.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/80655726d3d73c7e26f0879e.xlsx"},{"id":97745169,"identity":"0e01c611-9548-4f73-b5ba-ee87207127cd","added_by":"auto","created_at":"2025-12-09 00:23:44","extension":"xml","order_by":18,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":94658,"visible":true,"origin":"","legend":"","description":"","filename":"5dafd540a29f49fda37dac8686294d771enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/d9528d7c744bd87c771ed9f9.xml"},{"id":97745160,"identity":"4989612a-ca06-4f01-a4dd-50c5fc189bc5","added_by":"auto","created_at":"2025-12-09 00:23:44","extension":"tif","order_by":19,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":23128,"visible":true,"origin":"","legend":"","description":"","filename":"figure1.tif","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/e377f3e425b12d5a9290e4d5.tif"},{"id":97745152,"identity":"8d3a9727-91eb-43b0-997d-d12ce2afe594","added_by":"auto","created_at":"2025-12-09 00:23:44","extension":"png","order_by":20,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":8565,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/144a9efd132912dbb6371930.png"},{"id":97745167,"identity":"3411c1a0-0b27-4b59-bef8-a5c36f5178cc","added_by":"auto","created_at":"2025-12-09 00:23:44","extension":"xml","order_by":21,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":93004,"visible":true,"origin":"","legend":"","description":"","filename":"5dafd540a29f49fda37dac8686294d771structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/c250c25ee0e3781614582851.xml"},{"id":97896680,"identity":"99300380-87c5-4fbc-b79c-dab13fd46e84","added_by":"auto","created_at":"2025-12-10 15:36:52","extension":"html","order_by":22,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":100896,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/227c883cef8e73ae98d377d8.html"},{"id":97745134,"identity":"ce3f3677-206d-4975-a4d2-6e3ee91ffd77","added_by":"auto","created_at":"2025-12-09 00:23:43","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":13140,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve for comparisons of variable rate of D-dimer in traumatic patients with VTE.\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/aa3eda47ddc3d7f9617f584c.png"},{"id":100359843,"identity":"f540a63b-7d88-460e-b5af-5a2e87e5db9a","added_by":"auto","created_at":"2026-01-16 07:26:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":720803,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/4a617594-6ff1-4716-a4f3-631b1ce7343f.pdf"},{"id":97897210,"identity":"d2199627-2d95-4430-8c11-38e9d8183444","added_by":"auto","created_at":"2025-12-10 15:37:34","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":38508,"visible":true,"origin":"","legend":"","description":"","filename":"20200112.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/ce340e96ea762e4b40669681.xlsx"},{"id":97745141,"identity":"d12d5cc9-97b8-4523-8fe8-70a3556fa83e","added_by":"auto","created_at":"2025-12-09 00:23:43","extension":"xlsx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":1541372,"visible":true,"origin":"","legend":"","description":"","filename":"20200112.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/5aa5922d52cc77e17c0d9869.xlsx"},{"id":97895433,"identity":"7cce1813-d04a-4430-be34-c9687fa7069e","added_by":"auto","created_at":"2025-12-10 15:34:12","extension":"xlsx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":65566,"visible":true,"origin":"","legend":"","description":"","filename":"20210112.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/86240d440b9964e2777c8cd8.xlsx"},{"id":97745146,"identity":"ac098a55-4355-4ac5-85af-ede8eb71c275","added_by":"auto","created_at":"2025-12-09 00:23:43","extension":"xlsx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":1651257,"visible":true,"origin":"","legend":"","description":"","filename":"20210112.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/fdbb6a763e79612e517eb82b.xlsx"},{"id":97745149,"identity":"304995d7-884e-4375-860a-af969e979a31","added_by":"auto","created_at":"2025-12-09 00:23:44","extension":"xlsx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":100650,"visible":true,"origin":"","legend":"","description":"","filename":"20220112.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/945660d9bbb6b1e730d67cff.xlsx"},{"id":97897176,"identity":"c8693a5e-7344-4ad5-8d50-907f3b042a88","added_by":"auto","created_at":"2025-12-10 15:37:32","extension":"xlsx","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":1893362,"visible":true,"origin":"","legend":"","description":"","filename":"20220112.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/9929fdf86a947cf728db2c75.xlsx"},{"id":97896580,"identity":"911d8b43-3d44-4ba4-8771-56f4c654a7f7","added_by":"auto","created_at":"2025-12-10 15:36:47","extension":"xlsx","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":141120,"visible":true,"origin":"","legend":"","description":"","filename":"20230112.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/0ba76cd2c7bb8e929e230ad9.xlsx"},{"id":97745144,"identity":"d13a3a46-0e6a-4898-a6dd-ec4c7b208fcc","added_by":"auto","created_at":"2025-12-09 00:23:43","extension":"xlsx","order_by":9,"title":"","display":"","copyAsset":false,"role":"supplement","size":2160004,"visible":true,"origin":"","legend":"","description":"","filename":"20230112.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/f6481fd68641cd6a3ac3e0b9.xlsx"},{"id":97745154,"identity":"26c30adf-99f5-41b5-adbb-59d7d654f059","added_by":"auto","created_at":"2025-12-09 00:23:44","extension":"xlsx","order_by":10,"title":"","display":"","copyAsset":false,"role":"supplement","size":124621,"visible":true,"origin":"","legend":"","description":"","filename":"20240112.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/7ae13f91e19ff69a303494cd.xlsx"},{"id":97896965,"identity":"c81f3b64-9918-48eb-8eb8-cc23c10342a2","added_by":"auto","created_at":"2025-12-10 15:37:17","extension":"xlsx","order_by":11,"title":"","display":"","copyAsset":false,"role":"supplement","size":2253629,"visible":true,"origin":"","legend":"","description":"","filename":"20240112.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/c193bae0935f04318117b839.xlsx"},{"id":97745147,"identity":"806f7756-d7bc-456c-a781-44d0817520a7","added_by":"auto","created_at":"2025-12-09 00:23:44","extension":"xlsx","order_by":12,"title":"","display":"","copyAsset":false,"role":"supplement","size":78385,"visible":true,"origin":"","legend":"","description":"","filename":"20250106.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/1669e49f78fad702265aa561.xlsx"},{"id":97896915,"identity":"8228f441-4aed-4cc1-a74e-efd34ef43684","added_by":"auto","created_at":"2025-12-10 15:37:12","extension":"xlsx","order_by":13,"title":"","display":"","copyAsset":false,"role":"supplement","size":1305740,"visible":true,"origin":"","legend":"","description":"","filename":"20250106.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/dfc375ba212aa1a8685663f1.xlsx"},{"id":97894428,"identity":"b964f482-11db-4b6c-919b-c72dbd903494","added_by":"auto","created_at":"2025-12-10 15:32:29","extension":"xlsx","order_by":14,"title":"","display":"","copyAsset":false,"role":"supplement","size":170781,"visible":true,"origin":"","legend":"","description":"","filename":"StatisticalAnalysis.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7878480/v1/c9113da926ac57ee9c022299.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Variable Rate of D-dimer Predicts Venous Thromboembolism in Postoperative Fracture Patients: A Single-Center Retrospective Cohort Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eVenous thromboembolism (VTE), encompassing deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE), is a multifactorial condition arising from the interaction between acquired or inherited thrombophilic predispositions and transient clinical risk factors [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Patients undergoing orthopedic surgery are at increased risk of VTE, with reported incidence rates ranging from 6% to 61%, influenced by patient demographics, study duration, diagnostic methods, and the use of thromboprophylaxis [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePlasma D-dimer levels reflect fibrin formation and degradation, serving as a biomarker of active coagulation and fibrinolysis. Although a conventional threshold of 500 ng/mL is widely used in clinical practice, elevated D-dimer levels lack specificity for VTE and may also be observed in various non-thrombotic conditions, including traumatic fractures, malignancy, recent surgery, trauma, and infection [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Consequently, the utility of D-dimer as a standalone predictor of VTE remains limited.\u003c/p\u003e\u003cp\u003eFor early detection of VTE, identifying high-risk individuals through clinically relevant risk factors or laboratory biomarkers is both feasible and clinically meaningful. Substantial efforts have been made in orthopedics and other surgical disciplines to refine risk stratification, such as implementing age-adjusted D-dimer cutoffs to improve specificity and guide decision-making in patients with suspected VTE [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, neither standard nor age-adjusted D-dimer thresholds have been adequately validated for predicting postoperative VTE in patients with traumatic fractures. Moreover, no established biomarker is currently recommended for assessing VTE risk or enhancing predictive accuracy in this population.\u003c/p\u003e\u003cp\u003eGiven these limitations, there is a pressing need to identify a reliable clinical indicator that can complement or surpass the performance of D-dimer in VTE prediction. Emerging evidence suggests that dynamic monitoring of D-dimer levels may enhance early detection of VTE [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Based on these findings, we hypothesized that the D-dimer variability rate\u0026mdash;defined as the ratio of postoperative to preoperative D-dimer levels\u0026mdash;may provide superior predictive value compared to absolute D-dimer concentrations alone. Our retrospective study demonstrates that the D-dimer variability rate serves as a novel and potentially robust predictor of VTE in patients with traumatic fractures following orthopedic surgery.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003ePatients and Methods\u003c/h2\u003e\u003cp\u003eThis retrospective study was conducted at The Second Affiliated Hospital of Wenzhou Medical University in Wenzhou, China. A total of 80,422 patients with traumatic fractures (46,903 males and 33,519 females; mean age: 61.03\u0026thinsp;\u0026plusmn;\u0026thinsp;25.19 years) were enrolled between January 2020 and June 2025. Inclusion criteria were: (1) diagnosis of lower extremity, pelvic, spinal, craniofacial, or multiple compound fractures; and (2) age\u0026thinsp;\u0026ge;\u0026thinsp;18 years. Exclusion criteria included: (1) pathological fractures; (2) pre-injury anticoagulation therapy; (3) prior history of venous thromboembolism; (4) active malignancy; (5) pregnancy; (6) acute systemic infection; (7) hepatic failure; and (8) coagulopathy or other blood disorders. Clinical characteristics of patients with and without VTE are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic data\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\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eFactors\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTraumatic fracture\u003c/p\u003e\u003cp\u003ewith VTE (n\u0026thinsp;=\u0026thinsp;2813)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTraumatic fracture without VTE (n\u0026thinsp;=\u0026thinsp;77609)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e Value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eDVT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2743\u003c/p\u003e\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\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePreoperation stage\u003c/p\u003e\u003cp\u003eDay 1\u0026ndash;3 after operation\u003c/p\u003e\u003cp\u003eDay 4\u0026ndash;7 after operation\u003c/p\u003e\u003cp\u003eDay\u0026thinsp;\u0026gt;\u0026thinsp;8 after operation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e323\u003c/p\u003e\u003cp\u003e655\u003c/p\u003e\u003cp\u003e1122\u003c/p\u003e\u003cp\u003e643\u003c/p\u003e\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\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003ePTE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e70\u003c/p\u003e\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\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eGender\u003c/p\u003e\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\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1180\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e45723\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1633\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e31886\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eNo comorbidity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2293\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e65963\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.15\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eComorbidity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e520\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11646\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e219\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5615\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\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eDiabetes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2306\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.25\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eCoronary heart disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e336\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.23\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eOthers with 2 diseases at least\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e173\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3389\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eTypes of traumatic fracture\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e77609\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eUpper limb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9977\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\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eSpine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e422\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9575\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\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003ePelvis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e149\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3480\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eLower extremity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1485\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e39286\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eCompound fracture and others\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e721\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15291\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eSurgical options\u003c/p\u003e\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\u003cp\u003e0.16\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eORIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2280\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e60503\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eCRIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e603\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17106\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eD-dimer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.26\u0026thinsp;\u0026plusmn;\u0026thinsp;2.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.16\u0026thinsp;\u0026plusmn;\u0026thinsp;5.19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eVariable rate of D-dimer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.35\u0026thinsp;\u0026plusmn;\u0026thinsp;0.70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.79\u0026thinsp;\u0026plusmn;\u0026thinsp;1.77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eAbbreviations: VTE, venous thromboembolism; PTE, pulmonary thromboembolism; ORIF, open reduction and internal fixation; CRIF, closed reduction and internal fixation.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003ePlasma D-dimer Determination\u003c/h3\u003e\n\u003cp\u003ePlasma D-dimer levels were measured using a D-dimer assay kit (Dade Behring Co.) on the Sysmex CA-1500 automated coagulation analyzer employing the immunoturbidimetric method. Measurements were performed preoperatively (day 1) and postoperatively on days 1, 3, and 7. The variable rate of D-dimer was calculated as the ratio of postoperative to preoperative D-dimer levels.\u003c/p\u003e\n\u003ch3\u003eDiagnosis of DVT or PE\u003c/h3\u003e\n\u003cp\u003eAll trauma patients underwent routine screening for deep vein thrombosis using duplex ultrasonography. Computed tomography pulmonary angiography (CTPA) was performed in patients with clinical suspicion of PTE.\u003c/p\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eData were analyzed using SigmaPlot version 13.0. Categorical variables are presented as frequencies and proportions, while continuous variables are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. Comparisons between groups were performed using the chi-square test or Fisher\u0026rsquo;s exact test for categorical data, and Student\u0026rsquo;s t-test or Wilcoxon rank-sum test for continuous variables, as appropriate. Multiple logistic regression analysis was conducted to identify independent risk factors for VTE in this patient cohort. Receiver operating characteristic (ROC) curve analysis was used to determine optimal cut-off values for the D-dimer variable rate, with the threshold selected based on the maximum Youden index. A two-sided p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eDemographic Data\u003c/h2\u003e\u003cp\u003eThe mean age of traumatic fracture patients without VTE was 51.36\u0026thinsp;\u0026plusmn;\u0026thinsp;28.72 years, which was significantly lower than that of patients with VTE (68.13\u0026thinsp;\u0026plusmn;\u0026thinsp;26.65 years). Among patients with VTE, fracture distribution included 269 pelvic fractures, 522 spinal fractures, 336 upper limb or craniofacial bone fractures, 1,265 lower extremity fractures, and 421 complex fractures.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eDistribution of VTE Patients and D-dimer Variability in Traumatic Fracture\u003c/h3\u003e\n\u003cp\u003eA total of 323 patients were diagnosed with VTE preoperatively, 755 during postoperative days 1\u0026ndash;3, 1,292 between days 4\u0026ndash;7, and 443 after day 8, indicating a peak incidence in the early postoperative period. As shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, D-dimer levels in non-VTE patients were 5.56\u0026thinsp;\u0026plusmn;\u0026thinsp;3.08 mg/L preoperatively and 7.15\u0026thinsp;\u0026plusmn;\u0026thinsp;5.18 mg/L postoperatively. In contrast, VTE patients exhibited D-dimer levels of 5.25\u0026thinsp;\u0026plusmn;\u0026thinsp;2.96 mg/L preoperatively and 11.98\u0026thinsp;\u0026plusmn;\u0026thinsp;5.54 mg/L postoperatively. Notably, the the variable rate of D-dimer was markedly elevated in postoperative VTE patients (2.79\u0026thinsp;\u0026plusmn;\u0026thinsp;1.77) compared to preoperative non-VTE patients (1.35\u0026thinsp;\u0026plusmn;\u0026thinsp;0.70), with a statistically significant difference (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\n\u003ch3\u003eRisk Factors for Postoperative VTE in Traumatic Fracture Patients\u003c/h3\u003e\n\u003cp\u003eNo significant association was found between the D-dimer variability rate and comorbidities such as hypertension, diabetes, or coronary heart disease in either the VTE or non-VTE groups. Age and gender distributions were compared using the Student\u0026rsquo;s t-test and chi-square test, respectively, revealing statistically significant differences between the two groups (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The D-dimer variability rate was higher in elderly patients than in younger individuals. Furthermore, the incidence of VTE was significantly greater among patients with pelvic or lower extremity fractures compared to those with other fracture types. Female patients also demonstrated a higher prevalence of VTE relative to male patients.\u003c/p\u003e\u003cp\u003eIn univariate analysis, variables with \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05 were excluded, and the remaining factors were entered into multivariate logistic regression analysis. Age, D-dimer variability rate, and gender were identified as significant independent predictors of postoperative VTE. Results from both univariate and multivariate analyses are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMultiple logistic regression analysis for traumatic fracture patients with or without VTE\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRisk factors\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOdds ratio\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u0026thinsp;\u0026gt;\u0026thinsp;60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.24\u0026ndash;1.32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.38\u0026ndash;8.93\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUpper limb and or craniofacial bone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.00-1.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.29\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSpinal fracture\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.77\u0026ndash;3.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.41\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePelvis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.66\u0026ndash;3.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.51\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLower extremity fracture\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.03\u0026ndash;4.89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCompound fracture\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.97\u0026ndash;2.55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.09\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable rate of D-dimer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.94\u0026ndash;2.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eAbbreviations: CI, confidence interval.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eReceiver operating characteristic (ROC) curve analysis indicated that the D-dimer variability rate exhibited superior diagnostic performance compared to absolute D-dimer levels for detecting VTE in traumatic fracture patients. The area under the ROC curve (AUC) for the D-dimer variability rate was 0.82 (95% CI: 0.79\u0026ndash;0.84, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01). The optimal cutoff value, determined by maximizing the Youden index, was 2.0, yielding a sensitivity of 83.44% and a specificity of 88.60%.\u003c/p\u003e\u003cp\u003eThe odds ratio (OR) for the D-dimer variability rate was 1.74, confirming its role as an independent risk factor for postoperative VTE. The peak incidence of VTE occurred between postoperative days 3 and 7.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eVTE is a potentially life-threatening complication following traumatic injury. Elevated D-dimer levels are commonly observed in patients with traumatic fractures and are associated with an increased risk of VTE or PTE. However, D-dimer lacks specificity for the diagnosis of DVT and/or PTE. To the best of our knowledge, no previous studies have evaluated the variable rate of D-dimer as a predictor of VTE in postoperative orthopedic trauma patients. In this retrospective case-control study, we demonstrate that the variable rate of D-dimer has superior predictive value for VTE compared to absolute D-dimer levels alone.\u003c/p\u003e\u003cp\u003eNumerous studies have established that patients with traumatic fractures are at significantly increased risk of developing VTE [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Moreover, VTE remains a leading cause of morbidity and mortality among post-traumatic patients undergoing orthopedic surgery [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Traumatic fractures are associated with elevated D-dimer concentrations and a pronounced increase in VTE incidence [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Plasma D-dimer levels rise systematically after surgery, and significant differences have been observed between patients with and without VTE [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Hansen ES et al. reported that elevated plasma D-dimer levels correlate with a higher risk of incidental VTE [15]. Furthermore, the modified IMPROVE VTE score, when combined with elevated D-dimer, identified a nearly threefold increase in VTE risk among medically ill patients [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Our study confirms that D-dimer levels are elevated in traumatic fracture patients; however, not all such patients develop VTE complications.\u003c/p\u003e\u003cp\u003eThe utility of D-dimer as a diagnostic marker for VTE is limited. While it exhibits high negative predictive value for ruling out VTE, its positive predictive value is poor due to low specificity [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Notably, our findings indicate that the variable rate of D-dimer\u0026mdash;defined as the ratio of postoperative to preoperative D-dimer\u0026mdash;is more strongly correlated with VTE than D-dimer alone. Additionally, ROC analysis revealed a significantly greater discriminatory capacity for the variable rate of D-dimer in predicting postoperative VTE, whereas absolute D-dimer levels showed limited diagnostic accuracy. The optimal cutoff value for the variable rate of D-dimer was determined to be 2.0 after injury. These results suggest that monitoring the variable rate of D-dimer following trauma may improve VTE detection. Therefore, ultrasonography duplex and/or CTPA should be routinely considered in traumatic fracture patients when the variable rate of D-dimer exceeds 2.0. Importantly, our data also show that the peak incidence of VTE occurs between postoperative days 3 and 7.\u003c/p\u003e\u003cp\u003eThe association between age and VTE in fracture patients remains controversial. Some studies report that advanced age is an independent risk factor for thrombosis in adult trauma patients [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Conversely, Lapner et al. found no significant relationship between age and VTE incidence [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Despite these discrepancies, older age is generally recognized as a contributing factor to VTE development and is closely linked to age-adjusted D-dimer levels [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In our cohort, the incidence of VTE was significantly higher in elderly patients (age\u0026thinsp;\u0026gt;\u0026thinsp;60 years) compared to younger individuals (age\u0026thinsp;\u0026lt;\u0026thinsp;60 years). Multivariate logistic regression analysis confirmed that age is an independent risk factor for VTE in traumatic fracture patients over 60 years of age. Furthermore, the variable rate of D-dimer was markedly higher in elderly patients with VTE than in younger patients without VTE. Interestingly, however, we observed no significant increase in the variable rate of D-dimer in patients over 60 years of age regardless of VTE status, compared to those under 60. This suggests that, unlike conventional age-adjusted D-dimer thresholds, the variable rate of D-dimer does not appear to be influenced by age and may serve as a non-age-dependent screening tool for VTE in traumatic fracture patients.\u003c/p\u003e\u003cp\u003eGender is another debated independent risk factor for VTE [\u003cspan additionalcitationids=\"CR23 CR24\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Berndtson et al. found no difference in VTE incidence between male and female trauma patients, even after adjusting for menopausal status [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. In contrast, Arnesen et al. suggested that men may have a higher intrinsic risk of VTE than women across all age groups [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Nevertheless, most epidemiological studies report a 2- to 3-fold higher incidence of first-time VTE in women during their reproductive years compared to age-matched men [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. In our retrospective analysis, female traumatic fracture patients exhibited a higher risk of VTE than their male counterparts. Multivariate analysis further confirmed female sex as an independent predictor of VTE in this population. Notably, among female patients, the incidence of VTE was higher in postmenopausal women than in premenopausal women, which aligns with findings from Beyer-Westendorf et al. [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eData from the COMMAND VTE Registry indicate that the use of sex hormones, including combined oral contraceptives or hormone replacement therapy, substantially increases the risk of VTE, particularly in patients with an elevated intrinsic predisposition for thromboembolic complications [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Importantly, three large studies\u0026mdash;the MEGA study, the Hokusai-VTE study, and the RIETE registry\u0026mdash;have consistently demonstrated sex-related differences in the anatomical presentation of VTE, with PTE more frequently presenting as the initial manifestation in women compared to men [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Differences in D-dimer levels between males and females are diagnosis-dependent. However, no significant difference has been reported in the optimal D-dimer cutoff values for excluding PTE or DVT between the two sexes [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Notably, our retrospective analysis revealed that the variable rate of D-dimer was significantly higher in female traumatic fracture patients with VTE compared to those without VTE, which may partially explain the increased incidence of VTE observed in female fracture patients.\u003c/p\u003e\u003cp\u003eIn summary, age and sex are independent risk factors for VTE in traumatic fracture patients. Advanced age and female sex are associated with a higher variable rate of D-dimer. The variable rate of D-dimer appears to be a more effective diagnostic indicator for VTE than absolute D-dimer levels alone. Further studies are needed to validate the clinical utility of measuring the variable rate of D-dimer in this population.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eDVT deep vein thrombosis\u003c/p\u003e\u003cp\u003eVTE venous thromboembolism\u003c/p\u003e\u003cp\u003ePTE pulmonary thromboembolism\u003c/p\u003e\u003cp\u003eCTPA computed tomography pulmonary angiography\u003c/p\u003e\u003cp\u003eROC receiver operating characteristic\u003c/p\u003e\u003cp\u003eAUC area under the ROC curve\u003c/p\u003e\u003cp\u003eOR odds ratio\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective study was performed in accordance with the Declaration of Helsinki and the study protocol was approved by ethical standards of the Institutional Review Board of Ethics Committee of The Second Affiliated Hospital of Wenzhou medical University. Informed consent was obtained from each participant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe have no research data outside the submitted manuscript file.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author(s) received no financial support for the research, authorship, and/or publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization was led by X.-M.C. and X.-D.X.\u003c/p\u003e\n\u003cp\u003eThe methodology was designed by X.-M.C. and S.-Q.S.\u003c/p\u003e\n\u003cp\u003eData collection and investigation were performed by H.H., F.-H.J., and H.-Y.L.\u003c/p\u003e\n\u003cp\u003eFormal analysis was conducted by X.-M.C.\u003c/p\u003e\n\u003cp\u003eThe original draft was written by X.-M.C.\u003c/p\u003e\n\u003cp\u003eThe manuscript was reviewed and edited by S.-Q.S. and X.-D.X.\u003c/p\u003e\n\u003cp\u003eSupervision and project administration were the responsibility of X.-D.X.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone declared.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHeit JA, Spencer FA, White RH. The epidemiology of venous thromboembolism. J Thromb Thrombolysis. 2016.;41(1):3\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKahn SR, Shivakumar S. What's new in VTE risk and prevention in orthopedic surgery. Res Pract Thromb Haemost. 2020;4(3):366\u0026ndash;376.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCrous-Bou M, Harrington LB, Kabrhel C. Environmental and Genetic Risk Factors Associated with Venous Thromboembolism. Semin Thromb Hemost. 2016;42(8):808\u0026ndash;820.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFisher W. Managing hip fracture and lower limb surgery in the emergency setting: Potential role of non-vitamin K antagonist oral anticoagulants. J Trauma Acute Care Surg. 2017;82(6):1112\u0026ndash;1121.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLinkins LA, Takach Lapner S. Review of D-dimer testing: Good, Bad, and Ugly. Int J Lab Hematol. 2017;39 Suppl 1:98\u0026ndash;103.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSinger AJ, Zheng H, Francis S, Fermann GJ, Chang AM, Parry BA, Giordano N, Kabrhel C. D-dimer levels in VTE patients with distal and proximal clots. Am J Emerg Med. 2019;37(1):33\u0026ndash;37.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRiva N, Righini M, Camporese G, Iotti M, Bucherini E, Kamphuisen PW, Verhamme P, Douketis JD, Tonello C, Prandoni P, Ageno W, PALLADIO Study Investigators. Accuracy of age-adjusted D-dimer to rule out deep vein thrombosis in the elderly. Thromb Res. 2019;174:148\u0026ndash;150.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRiva N, Camporese G, Iotti M, Bucherini E, Righini M, Kamphuisen PW, Verhamme P, Douketis J D, Tonello C, Prandoni P, Ageno W, PALLADIO Study Investigators. Age-adjusted D-dimer to rule out deep vein thrombosis: findings from the PALLADIO algorithm. J Thromb Haemost. 2018;16:271\u0026ndash;278.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJohnson ED, Schell JC, Rodgers GM. The D-dimer assay. Am J Hematol. 2019;94(7):833\u0026ndash;839.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMacDonald DRW, Neilly D, Schneider PS, Bzovsky S, Sprague S, Axelrod D, Poolman RW, Frihagen F, Bhandari M, Swiontkowski M, Schemitsch EH, Stevenson IM; FAITH Investigators; HEALTH Investigators. Venous Thromboembolism in Hip Fracture Patients: A Subanalysis of the FAITH and HEALTH Trials. J Orthop Trauma. 2020;34 Suppl 3:S70-S75.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYoon JY, Kim S, Chang JS, Yoon PW, Kim JW. Venous thromboembolism after delayed surgery for a hip fracture: A retrospective cohort study. Geriatr Gerontol Int. 2020;20(12):1151\u0026ndash;1156\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFlevas DA, Megaloikonomos PD, Dimopoulos L, Mitsiokapa E, Koulouvaris P, Mavrogenis AF. Thromboembolism prophylaxis in orthopaedics: an update. EFORT Open Rev. 2018;3(4):136\u0026ndash;148.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWhiting PS, Jahangir AA. Thromboembolic Disease After Orthopedic Trauma. Orthop Clin North Am. 2016;47(2):335\u0026ndash;344.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYang Y, Zan P, Gong J, Cai M. d-Dimer as a Screening Marker for Venous Thromboembolism After Surgery Among Patients Younger Than 50 With Lower Limb Fractures. Clin Appl Thromb Hemost. 2017;23(1):78\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e5 Hansen ES, Rinde FB, Edvardsen MS, Hindberg K, Latysheva N, Aukrust P, Ueland T, Michelsen AE, Hansen JB, Br\u0026aelig;kkan SK, Morelli VM. Elevated plasma D-dimer levels are associated with risk of future incident venous thromboembolism. Thromb Res. 2021;208:121\u0026ndash;126.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSpyropoulos AC, Lipardi C, Xu J, Peluso C, Spiro TE, De Sanctis Y, Barnathan ES, Raskob GE. Modified IMPROVE VTE Risk Score and Elevated D-Dimer Identify a High Venous Thromboembolism Risk in Acutely Ill Medical Population for Extended Thromboprophylaxis. TH Open. 2020;4(1):e59-e65.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNiikura T, Sakai Y, Lee SY, Iwakura T, Nishida K, Kuroda R, Kurosaka M. D-dimer levels to screen for venous thromboembolism in patients with fractures caused by high-energy injuries. J Orthop Sci. 2015;20(4):682\u0026ndash;688.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHuang CH, Wang WH, Kor CT, Hsiao CH, Chang CC. Risk of venous thromboembolism in elderly patients with vertebral compression fracture: A population-based case-control study. Medicine (Baltimore). 2020;99(18):e20072.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNastasi AJ, Canner JK, Lau BD, Streiff MB, Aboagye JK, Kraus PS, Hobson DB, Van Arendonk KJ, Haut ER. Characterizing the relationship between age and venous thromboembolism in adult trauma patients: findings from the National Trauma Data Bank and the National Inpatient Sample. J Surg Res. 2017;216:115\u0026ndash;122.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTakach Lapner S, Julian JA, Linkins L-A, Bates SM, Kearon C. Questioning the use of an age-adjusted D-dimer threshold to exclude venous thromboembolism: analysis of individual patient data from two diagnostic studies. \u003cem\u003eJ Thromb Haemost\u003c/em\u003e 2016; 14(10): 1953\u0026ndash;1959.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHaase C, Joergensen M, Ellervik C, Joergensen MK, Bathum L. Age- and sex-dependent reference intervals for D-dimer: evidence for a marked increase by age. Thromb Res. 2013;132(6):676\u0026ndash;680.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eReagh JJ, Zheng H, Stolz U, Parry BA, Chang AM, House SL, Giordano NJ, Cohen J, Singer AJ, Francis S, Prochaska JH, Zeserson E, Wild PS, Limkakeng AT Jr, Walters EL, LoVecchio F, Theodoro D, Hollander JE, Kabrhel C, Fermann GJ. Sex-related differences in D-dimer levels for venous thromboembolism screening. Acad Emerg Med. 2021;28(8):873\u0026ndash;881.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLegnani C, Cini M, Cosmi B, Carraro P, Tripodi A, Erba N, Palareti G. Age and gender specific cut-off values to improve the performance of D-dimer assays to predict the risk of venous thromboembolism recurrence. Intern Emerg Med. 2013;8(3):229\u0026ndash;236.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGiustozzi M, Valerio L, Agnelli G, Becattini C, Fronk EM, Klok FA, Konstantinides SV, Vedovati MC, Cohen AT, Barco S. Sex-specific differences in the presentation, clinical course, and quality of life of patients with acute venous thromboembolism according to baseline risk factors. Insights from the PREFER in VTE. Eur J Intern Med. 2021;88:43\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYoshikawa Y, Yamashita Y, Morimoto T, Amano H, Takase T, Hiramori S, Kim K, Oi M, Akao M, Kobayashi Y, Toyofuku M, Izumi T, Tada T, Chen PM, Murata K, Tsuyuki Y, Saga S, Sasa T, Sakamoto J, Kinoshita M, Togi K, Mabuchi H, Takabayashi K, Shiomi H, Kato T, Makiyama T, Ono K, Kimura T; COMMAND VTE Registry Investigators. Sex Differences in Clinical Characteristics and Outcomes of Patients With Venous Thromboembolism-From the COMMAND VTE Registry. Circ J. 2019;83(7):1581\u0026ndash;1589.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBerndtson AE, Costantini TW, Smith AM, Kobayashi L, Coimbra R.Does sex matter? Effects on venous thromboembolism risk in screened trauma patients. J Trauma Acute Care Surg. 2016;81(3):493\u0026ndash;499.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eArnesen CAL, Veres K, Horv\u0026aacute;th-Puh\u0026oacute; E, Hansen J-B, S\u0026oslash;rensen HT, Br\u0026aelig;kkan SK. Estimated lifetime risk of venous thromboembolism in men and women in a Danish nationwide cohort: impact of competing risk of death. Eur J Epidemiol. 2022; 37(2): 195\u0026ndash;203.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSex-specific aspects of venous thromboembolism: What is new and what is next? Scheres LJJ, van Hylckama Vlieg A, Cannegieter SC. Res Pract Thromb Haemost. 2022;6(4):e12722.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMarshall AL, Bartley AC, Ashrani AA, Pruthi RK, Durani U, Gonsalves WI, Kapoor P, Hashmi SK, Siddiqui MA, Go RS. Sex-based disparities in venous thromboembolism outcomes: A National Inpatient Sample (NIS)-based analysis. Vasc Med. 2017;22(2):121\u0026ndash;127.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBeyer-Westendorf J, Bauersachs R, Hach-Wunderle V, Zotz RB, Rott H. Sex hormones and venous thromboembolism - from contraception to hormone replacement therapy. Vasa. 2018;47(6):441\u0026ndash;450.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eScheres LJJ, Brekelmans MPA, Beenen LFM, B\u0026uuml;ller HR, Cannegieter SC, Middeldorp S. Sex-specific differences in the presenting location of a first venous thromboembolism. J Thromb Haemost. 2017;15(7):1344\u0026ndash;1350.\u003c/span\u003e\u003c/li\u003e\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":"D-dimer, Variable rate of D-dimer, Traumatic fracture, Venous thromboembolism, Pulmonary embolism","lastPublishedDoi":"10.21203/rs.3.rs-7878480/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7878480/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eThe correlation between plasma D-dimer levels and deep vein thrombosis (DVT) remains inconsistent across studies. This study aimed to investigate whether the variable rate of D-dimer is a more accurate predictor of venous thromboembolism (VTE) compared to D-dimer alone.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eDemographic data, fracture classification, and D-dimer levels were collected. The variable rate of D-dimer was defined as the ratio of postoperative D-dimer to preoperative D-dimer. Duplex ultrasonography was used to evaluate DVT in the lower extremities, while computed tomography pulmonary angiography was conducted for patients suspected of having pulmonary thromboembolism (PTE).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA total of 77,609 traumatic fracture patients without VTE (mean age: 51.36\u0026thinsp;\u0026plusmn;\u0026thinsp;28.72 years) and 2,813 patients with VTE (mean age: 68.13\u0026thinsp;\u0026plusmn;\u0026thinsp;26.65 years) were included. Among the VTE patients, 36 had upper limb fractures, 522 had spine fractures, 269 had pelvic fractures, 1,265 had lower extremity fractures, and 721 had compound or other types of fractures. Of these, 2,743 patients developed lower extremity venous thromboembolism, and 70 suffered from PTE. The variable rate of D-dimer was significantly higher in postoperative traumatic fracture patients with VTE (2.79\u0026thinsp;\u0026plusmn;\u0026thinsp;1.77) compared to preoperative patients without VTE (1.35\u0026thinsp;\u0026plusmn;\u0026thinsp;0.70). Using a cutoff point of 2.0 for the variable rate of D-dimer, sensitivity and specificity were 83.44% and 88.60%, respectively. Multivariate analysis revealed that age\u0026thinsp;\u0026gt;\u0026thinsp;60 years, female sex, and lower extremity fractures were independent risk factors for VTE.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThe variable rate of D-dimer is strongly correlated with VTE in postoperative traumatic fracture patients. It serves as a useful predictor of VTE, particularly in elderly patients, females, and those with lower extremity fractures.\u003c/p\u003e","manuscriptTitle":"Variable Rate of D-dimer Predicts Venous Thromboembolism in Postoperative Fracture Patients: A Single-Center Retrospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-09 00:23:38","doi":"10.21203/rs.3.rs-7878480/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":"d6210196-4c3a-4e04-aeb6-8db9e9201ba5","owner":[],"postedDate":"December 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-10T10:39:16+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-09 00:23:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7878480","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7878480","identity":"rs-7878480","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}