Recurrent venous thromboembolism: current evidence on risk stratification and prediction models_West China Medical Journal

Authors：

LIU Hong ^1,2 , ZHANG Yonggang ^1,3 , LI Nian ⁴ , LIAO Xiaoyang ¹ ,  JIA Yu ¹

1. Department of General Practice, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Department of Cardiology, Chengdu Eighth People’s Hospital, Chengdu, Sichuan 610083, P. R. China;
3. Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
4. Medical Administration Department, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding?author：

JIA Yu, Email: jiayu@wchscu.cn

Keywords：

Venous thromboembolism; risk factor; anticoagulation; risk prediction model

DOI：

10.7507/1002-0179.202511115

Video：

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Abstract Full text Figures/Tables Video References Cited by

Venous thromboembolism (VTE) carries a high risk of recurrence, making precise identification of high risk individuals crucial for optimizing anticoagulation strategies. This review summarizes current evidence on risk factors and prediction models for recurrent VTE. Recurrence is driven by a combination of baseline characteristics (e.g., male sex, non-O blood group), acquired clinical factors (e.g., initial proximal deep vein thrombosis or pulmonary embolism), and laboratory markers (e.g., D-dimer). Although multiple prediction models have been developed across diverse populations, they vary considerably in variable composition, target cohorts, and extent of external validation, and generally lack dynamic predictive capabilities. Future efforts should prioritize enhancing model generalizability, dynamic risk assessment, and clinical utility to guide individualized anticoagulation decisions and ultimately reduce recurrence rates.

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7.	White RH, Dager WE, Zhou H, et al. Racial and gender differences in the incidence of recurrent venous thromboembolism. Thromb Haemost, 2006, 96(3): 267-273.
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9.	Roach RE, Lijfering WM, Tait RC, et al. Sex difference in the risk of recurrent venous thrombosis: a detailed analysis in four European cohorts. J Thromb Haemost, 2015, 13(10): 1815-1822.
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1. Becattini C, Agnelli G. Acute treatment of venous thromboembolism. Blood, 2020, 135(5): 305-316.
2. Martinez C, Cohen AT, Bamber L, et al. Epidemiology of first and recurrent venous thromboembolism: a population-based cohort study in patients without active cancer. Thromb Haemost, 2014, 112(2): 255-263.
3. Heit JA, Ashrani A, Crusan DJ, et al. Reasons for the persistent incidence of venous thromboembolism. Thromb Haemost, 2017, 117(2): 390-400.
4. Law Y, Chan YC, Cheng SWK. Epidemiological updates of venous thromboembolism in a Chinese population. Asian J Surg, 2018, 41(2): 176-182.
5. Scheres LJJ, van Hylckama Vlieg A, Cannegieter SC. Sex-specific aspects of venous thromboembolism: what is new and what is next?. Res Pract Thromb Haemost, 2022, 6(4): e12722.
6. Siegel RL, Miller KD, Wagle NS, et al. Cancer statistics, 2023. CA Cancer J Clin, 2023, 73(1): 17-48.
7. White RH, Dager WE, Zhou H, et al. Racial and gender differences in the incidence of recurrent venous thromboembolism. Thromb Haemost, 2006, 96(3): 267-273.
8. Khan F, Rahman A, Carrier M, et al. Long term risk of symptomatic recurrent venous thromboembolism after discontinuation of anticoagulant treatment for first unprovoked venous thromboembolism event: systematic review and Meta-analysis. BMJ, 2019, 366: l4363.
9. Roach RE, Lijfering WM, Tait RC, et al. Sex difference in the risk of recurrent venous thrombosis: a detailed analysis in four European cohorts. J Thromb Haemost, 2015, 13(10): 1815-1822.
10. 劉暢, 黎俊雅, 朱忠立, 等. 急性肺血栓栓塞癥患者復發靜脈血栓栓塞的危險因素研究. 實用心腦肺血管病雜志, 2023, 31(4):69-72.
11. 喬夢圓, 秦夢真, 王海燕, 等. 靜脈血栓栓塞癥復發風險預測模型的系統評價. 中國護理管理, 2024, 24(2): 237-244.
12. Lutsey PL, Zakai NA. Epidemiology and prevention of venous thromboembolism. Nat Rev Cardiol, 2023, 20(4): 248-262.
13. Lutsey PL, Folsom AR. Taller women are at greater risk of recurrent venous thromboembolism: the Iowa women’s health study. Am J Hematol, 2012, 87(7): 716-717.
14. Flinterman LE, van Hylckama Vlieg A, Rosendaal FR, et al. Body height, mobility, and risk of first and recurrent venous thrombosis. J Thromb Haemost, 2015, 13(4): 548-554.
15. Rejt? J, K?nigsbrügge O, Grilz E, et al. Influence of blood group, von Willebrand factor levels, and age on factor VIII levels in non-severe haemophilia A. J Thromb Haemost, 2020, 18(5): 1081-1086.
16. Gándara E, Kovacs MJ, Kahn SR, et al. Non-OO blood type influences the risk of recurrent venous thromboembolism. A cohort study. Thromb Haemost, 2013, 110(6): 1172-1179.
17. Baudouy D, Moceri P, Chiche O, et al. B blood group: a strong risk factor for venous thromboembolism recurrence. Thromb Res, 2015, 136(1): 107-111.
18. Dahlb?ck B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci U S A, 1993, 90(3): 1004-1008.
19. Weingarz L, Schindewolf M, Schwonberg J, et al. Thrombophilia and risk of VTE recurrence according to the age at the time of first VTE manifestation. Vasa, 2015, 44(4): 313-323.
20. Méan M, Limacher A, Stalder O, et al. Do factor V leiden and prothrombin G20210A mutations predict recurrent venous thromboembolism in older patients?. Am J Med, 2017, 130(10): 1220. e17-1220. e22.
21. Marchiori A, Mosena L, Prins MH, et al. The risk of recurrent venous thromboembolism among heterozygous carriers of factor V Leiden or prothrombin G20210A mutation. A systematic review of prospective studies. Haematologica, 2007, 92(8): 1107-1114.
22. Eppenberger D, Nilius H, Anagnostelis B, et al. Current knowledge on factor v leiden mutation as a risk factor for recurrent venous thromboembolism: a systematic review and meta-analysis. Front Cardiovasc Med, 2022, 9: 883986.
23. Wootton DM, Ku DN. Fluid mechanics of vascular systems, diseases, and thrombosis. Annu Rev Biomed Eng, 1999, 1: 299-329.
24. Stalker TJ, Traxler EA, Wu J, et al. Hierarchical organization in the hemostatic response and its relationship to the platelet-signaling network. Blood, 2013, 121(10): 1875-1885.
25. Douketis JD, Crowther MA, Foster GA, et al. Does the location of thrombosis determine the risk of disease recurrence in patients with proximal deep vein thrombosis?. Am J Med, 2001, 110(7): 515-519.
26. Law JP, Pickup L, Townend JN, et al. Anticoagulant strategies for the patient with chronic kidney disease. Clin Med (Lond), 2020, 20(2): 151-155.
27. Goto S, Haas S, Ageno W, et al. Assessment of outcomes among patients with venous thromboembolism with and without chronic kidney disease. JAMA Netw Open, 2020, 3(10): e2022886.
28. Jenkins EO, Schiff D, Mackman N, et al. Venous thromboembolism in malignant gliomas. J Thromb Haemost, 2010, 8(2): 221-227.
29. Streiff MB. Thrombosis in the setting of cancer. Hematology am soc hematol educ program, 2016, 2016(1): 196-205.
30. Nishimoto Y, Yamashita Y, Morimoto T, et al. Risk factors of recurrence in patients with cancer-associated venous thromboembolism. Eur J Intern Med, 2021, 91: 98-101.
31. Heit JA, Lahr BD, Ashrani AA, et al. Predictors of venous thromboembolism recurrence, adjusted for treatments and interim exposures: a population-based case-cohort study. Thromb Res, 2015, 136(2): 298-307.
32. Nemeth B, Lijfering WM, Nelissen RGHH, et al. Risk and risk factors associated with recurrent venous thromboembolism following surgery in patients with history of venous thromboembolism. JAMA Netw Open, 2019, 2(5): e193690.
33. Gouzoulis MJ, Joo PY, Kammien AJ, et al. Risk factors for venous thromboembolism following fractures isolated to the foot and ankle fracture. PLoS One, 2022, 17(10): e0276548.
34. Sun L, Zhang B. The digestive system and autoimmunity. BMC Immunol, 2023, 24(1): 36.
35. Borjas-Howard JF, Leeuw K, Rutgers A, et al. Risk of recurrent venous thromboembolism in autoimmune diseases: a systematic review of the literature. Semin Thromb Hemost, 2019, 45(2):141-149.
36. Borjas Howard JF, Ruiz-Sada P, de Leeuw K, et al. Risk of recurrent venous thromboembolism in patients with autoimmune diseases: data from the registro informatizado de enfermedad tromboembólica (RIETE) registry. Br J Haematol, 2021, 194(1): 195-199.
37. Wilkowska A, Kujawska-Danecka H, Hajduk A. Risk and prophylaxis of venous thromboembolism in hospitalized psychiatric patients. A review. Psychiatr Pol, 2018, 52(3): 421-435.
38. Hajjiah A, Maadarani O, Bitar Z, et al. Antipsychotic drugs may contribute to venous thromboembolism - a case report and review literature. JRSM Open, 2023, 14(1): 20542704221132142.
39. Nakamura M, Yamada N, Oda E, et al. Predictors of venous thromboembolism recurrence and the bleeding events identified using a Japanese healthcare database. J Cardiol, 2017, 70(2):155-162.
40. von K?nel R, Margani A, Stauber S, et al. Depressive symptoms as a novel risk factor for recurrent venous thromboembolism: a longitudinal observational study in patients referred for thrombophilia investigation. PLoS One, 2015, 10(5): e0125858.
41. Yoon HJ. Coagulation abnormalities and bleeding in pregnancy: an anesthesiologist’s perspective. Anesth Pain Med (Seoul), 2019, 14(4): 371-379.
42. Algahtani H, Bazaid A, Shirah B, et al. Cerebral venous sinus thrombosis in pregnancy and puerperium: a comprehensive review. Brain Circ, 2022, 8(4): 180-187.
43. Galambosi PJ, Ulander VM, Kaaja RJ. The incidence and risk factors of recurrent venous thromboembolism during pregnancy. Thromb Res, 2014, 134(2): 240-245.
44. Palareti G, Cosmi B, Legnani C, et al. D-dimer testing to determine the duration of anticoagulation therapy. N Engl J Med, 2006, 355(17): 1780-1789.
45. 王勇, 趙亞丹, 張洪亮, 等. N 末端 B 型利鈉肽原與急性肺血栓栓塞癥后血栓復發的相關性分析. 中國心血管雜志, 2020, 25(2): 116-120.
46. Zhao Y, Cheng Y, Luo Y, et al. International normalized ratio predicts recurrence and bleeding in patients with acute venous thromboembolism who undergo direct oral anticoagulants. Clin Appl Thromb Hemost, 2024, 30: 10760296241246004.
47. Aleidan FAS. The cumulative incidence and risk factors of recurrent venous thromboembolism in the elderly. Vasc Health Risk Manag, 2020, 16: 437-443.
48. Eichinger S, Hron G, Bialonczyk C, et al. Overweight, obesity, and the risk of recurrent venous thromboembolism. Arch Intern Med, 2008, 168(15): 1678-1683.
49. Davidson BL, Büller HR, Decousus H, et al. Effect of obesity on outcomes after fondaparinux, enoxaparin, or heparin treatment for acute venous thromboembolism in the Matisse trials. J Thromb Haemost, 2007, 5(6): 1191-1194.
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