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Prediction of recurrent venous thrombosis in all patients with a first venous thrombotic event: The Leiden Thrombosis Recurrence Risk Prediction model (L-TRRiP)


Autoři: Jasmijn F. Timp aff001;  Sigrid K. Braekkan aff002;  Willem M. Lijfering aff001;  Astrid van Hylckama Vlieg aff001;  John-Bjarne Hansen aff002;  Frits R. Rosendaal aff001;  Saskia le Cessie aff004;  Suzanne C. Cannegieter aff001
Působiště autorů: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands aff001;  K. G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT–The Arctic University of Norway, Tromsø, Norway aff002;  Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway aff003;  Department of Medical Statistics, Leiden University Medical Center, Leiden, the Netherlands aff004;  Department of Internal Medicine, Section Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands aff005
Vyšlo v časopise: Prediction of recurrent venous thrombosis in all patients with a first venous thrombotic event: The Leiden Thrombosis Recurrence Risk Prediction model (L-TRRiP). PLoS Med 16(10): e32767. doi:10.1371/journal.pmed.1002883
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pmed.1002883

Souhrn

Background

Recurrent venous thromboembolism (VTE) is common. Current guidelines suggest that patients with unprovoked VTE should continue anticoagulants unless they have a high bleeding risk, whereas all others can stop. Prediction models may refine this dichotomous distinction, but existing models apply only to patients with unprovoked first thrombosis. We aimed to develop a prediction model for all patients with first VTE, either provoked or unprovoked.

Methods and findings

Data were used from two population-based cohorts of patients with first VTE from the Netherlands (Multiple Environment and Genetic Assessment of Risk Factors for Venous Thrombosis [MEGA] follow-up study, performed from 1994 to 2009; model derivation; n = 3,750) and from Norway (Tromsø study, performed from 1999 to 2016; model validation; n = 663). Four versions of a VTE prediction model were developed: model A (clinical, laboratory, and genetic variables), model B (clinical variables and fewer laboratory markers), model C (clinical and genetic factors), and model D (clinical variables only). The outcome measure was recurrent VTE. To determine the discriminatory power, Harrell’s C-statistic was calculated. A prognostic score was assessed for each patient. Kaplan-Meier plots for the observed recurrence risks were created in quintiles of the prognostic scores. For each patient, the 2-year predicted recurrence risk was calculated. Models C and D were validated in the Tromsø study.

During 19,201 person-years of follow-up (median duration 5.7 years) in the MEGA study, 507 recurrences occurred. Model A had the highest predictive capability, with a C-statistic of 0.73 (95% CI 0.71–0.76). The discriminative performance was somewhat lower in the other models, with C-statistics of 0.72 for model B, 0.70 for model C, and 0.69 for model D. Internal validation showed a minimal degree of optimism bias. Models C and D were externally validated, with C-statistics of 0.64 (95% CI 0.62–0.66) and 0.65 (95% CI 0.63–0.66), respectively. According to model C, in 2,592 patients with provoked first events, 367 (15%) patients had a predicted 2-year risk of >10%, whereas in 1,082 patients whose first event was unprovoked, 484 (45%) had a predicted 2-year risk of <10%. A limitation of both cohorts is that laboratory measurements were missing in a substantial proportion of patients, which therefore were imputed.

Conclusions

The prediction model we propose applies to patients with provoked or unprovoked first VTE—except for patients with (a history of) cancer—allows refined risk stratification, and is easily usable. For optimal individualized treatment, a management study in which bleeding risks are also taken into account is necessary.

Klíčová slova:

Cancer risk factors – Deep vein thrombosis – Human genetics – Obstetric procedures – Thrombosis – Venous thromboembolism


Zdroje

1. Hansson PO, Sörbo J, Eriksson H. Recurrent venous thromboembolism after deep vein thrombosis: incidence and risk factors. Arch Intern Med. 2000;160:769–74. doi: 10.1001/archinte.160.6.769 10737276

2. Prandoni P, Noventa F, Ghirarduzzi A, Pengo V, Bernardi E, Pesavento R, et al. The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica. 2007;92:199–205. doi: 10.3324/haematol.10516 17296569

3. Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149:315–352. doi: 10.1016/j.chest.2015.11.026 26867832

4. Boutitie F, Pinede L, Schulman S, Agnelli G, Raskob G, Julian J, et al. Influence of preceding length of anticoagulant treatment and initial presentation of venous thromboembolism on risk of recurrence after stopping treatment: analysis of individual participants’ data from seven trials. BMJ. 2011;342:d3036. doi: 10.1136/bmj.d3036 21610040

5. Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, et al.; EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363:2499–510. doi: 10.1056/NEJMoa1007903 21128814

6. Kyrle PA, Kammer M, Eischer L, Weltermann A, Minar E, Hirschl M, et al. The long-term recurrence risk of patients with unprovoked venous thromboembolism: an observational cohort study. J Thromb Haemost. 2016;14:2402–2409. doi: 10.1111/jth.13524 27696701

7. van Rein N, Lijfering WM, Bos MH, Herruer MH, Vermaas HW, van der Meer FJ, et al. Objectives and Design of BLEEDS: A Cohort Study to Identify New Risk Factors and Predictors for Major Bleeding during Treatment with Vitamin K Antagonists. PLoS ONE. 2016;11(12):e0164485. doi: 10.1371/journal.pone.0164485 27935941

8. Chong LY, Fenu E, Stansby G, Hodgkinson S; Guideline Development Group. Management of venous thromboembolic diseases and the role of thrombophilia testing: summary of NICE guidance. BMJ. 2012;344:e3979. doi: 10.1136/bmj.e3979 22740565

9. Lijfering WM, Timp JF, Cannegieter SC. Predicting the risk of recurrent venous thrombosis: what the future might bring. J Thromb Haemost. 2019;17(9):1522–1526. doi: 10.1111/jth.14534 31220398

10. Ensor J, Riley RD, Moore D, Snell KI, Bayliss S, Fitzmaurice D. Systematic review of prognostic models for recurrent venous thromboembolism (VTE) post-treatment of first unprovoked VTE. BMJ Open. 2016;6:e011190. doi: 10.1136/bmjopen-2016-011190 27154483

11. Kearon C, Ageno W, Cannegieter SC, Cosmi B, Geersing GJ, Kyrle PA; Subcommittees on Control of Anticoagulation, and Predictive and Diagnostic Variables in Thrombotic Disease. Categorization of patients as having provoked or unprovoked venous thromboembolism: guidance from the SSC of ISTH. J Thromb Haemost. 2016;14:1480–3. doi: 10.1111/jth.13336 27428935

12. Middeldorp S, Iorio A. Oral contraceptive use is a provoking factor for venous thromboembolism. BMJ. 2017;357:j2073. doi: 10.1136/bmj.j2073 28450404

13. Timp JF, Lijfering WM, le Cessie S, Rosendaal FR, Cannegieter SC. Risk prediction of recurrent venous thrombosis; where are we now and what can we add? J Thromb Haemost. 2019;17(9):1527–1534. doi: 10.1111/jth.14535 31188515

14. Zhu T, Martinez I, Emmerich J. Venous thromboembolism: risk factors for recurrence. Arterioscler Thromb Vasc Biol. 2009;29:298–310. doi: 10.1161/ATVBAHA.108.182428 19228602

15. Rodger MA, Kahn SR, Wells PS, Anderson DA, Chagnon I, Le Gal G, et al. Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy. CMAJ. 2008;179:417–26. doi: 10.1503/cmaj.080493 18725614

16. Eichinger S, Heinze G, Jandeck LM, Kyrle PA. Risk assessment of recurrence in patients with unprovoked deep vein thrombosis or pulmonary embolism: the Vienna prediction model. Circulation. 2010;121:1630–6. doi: 10.1161/CIRCULATIONAHA.109.925214 20351233

17. Tosetto A, Iorio A, Marcucci M, Baglin T, Cushman M, Eichinger S, et al. Predicting disease recurrence in patients with previous unprovoked venous thromboembolism: a proposed prediction score (DASH). J Thromb Haemost. 2012;10(6):1019–25. doi: 10.1111/j.1538-7836.2012.04735.x 22489957

18. Rodger MA, Le Gal G, Anderson DR, Schmidt J, Pernod G, Kahn SR, et al.; REVERSE II Study Investigators. Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: multinational prospective cohort management study. BMJ. 2017;356:j1065. doi: 10.1136/bmj.j1065 28314711

19. Marcucci M, Iorio A, Douketis JD, Eichinger S, Tosetto A, Baglin T, et al. Risk of recurrence after a first unprovoked venous thromboembolism: external validation of the Vienna Prediction Model with pooled individual patient data. J Thromb Haemost. 2015;13:775–81. doi: 10.1111/jth.12871 25660555

20. Tosetto A, Testa S, Martinelli I, Poli D, Cosmi B, Lodigiani C, et al. External validation of the DASH prediction rule: a retrospective cohort study. J Thromb Haemost. 2017;15:1963–1970. doi: 10.1111/jth.13781 28762665

21. Wang S, Wu W, Zhou X. App Store Analysis: Using Regression Model for App Downloads Prediction. In: Che W, et al., editors. Social Computing. ICYCSEE 2016: Communications in Computer and Information Science, vol 623; 2016 Aug 20–22; Harbin, China. Singapore: Springer; 2016.

22. Nemeth B, Timp JF, van Hylckama Vlieg A, Rosendaal FR, Cannegieter SC. High risk of recurrent venous thrombosis in patients with lower-leg cast immobilization. J Thromb Haemost. 2018;16:2218–2222. doi: 10.1111/jth.14278 30160361

23. Blom JW, Doggen CJ, Osanto S, Rosendaal FR. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA. 2005;293:715–22. doi: 10.1001/jama.293.6.715 15701913

24. Ocak G, Vossen CY, Verduijn M, Dekker FW, Rosendaal FR, Cannegieter SC, et al. Risk of venous thrombosis in patients with major illnesses: results from the MEGA study. J Thromb Haemost. 2013;11:116–23. doi: 10.1111/jth.12043 23106832

25. Flinterman LE, van Hylckama Vlieg A, Cannegieter SC, Rosendaal FR. Long-term survival in a large cohort of patients with venous thrombosis: incidence and predictors. PLoS Med. 2012;9(1):e1001155. doi: 10.1371/journal.pmed.1001155 22253578

26. Timp JF, Lijfering WM, Flinterman LE, van Hylckama Vlieg A, le Cessie S, Rosendaal FR, et al. Predictive value of factor VIII levels for recurrent venous thrombosis: results from the MEGA follow-up study. J Thromb Haemost. 2015;13:1823–32. doi: 10.1111/jth.13113 26270389

27. Konstantinides SV, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Galiè N, et al.; Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2014 Nov 14;35(43):3033–69, 3069a-3069k.

28. van Hylckama Vlieg A, Flinterman LE, Bare LA, Cannegieter SC, Reitsma PH, Arellano AR, et al. Genetic variations associated with recurrent venous thrombosis. Circ Cardiovasc Genet. 2014;7:806–13. doi: 10.1161/CIRCGENETICS.114.000682 25210051

29. Rubin DB. Multiple imputation for nonresponse in surveys. New York: Wiley; 1987.

30. Kearon C, Iorio A, Palareti G; Subcommittee on Control of Anticoagulation of the SSC of the ISTH. Risk of recurrent venous thromboembolism after stopping treatment in cohort studies: recommendation for acceptable rates and standardized reporting. J Thromb Haemost. 2010;8:2313–5. doi: 10.1111/j.1538-7836.2010.03991.x 20738761

31. Jacobsen BK, Eggen AE, Mathiesen EB, Wilsgaard T, Njolstad I. Cohort profile: the Tromsø Study. Int J Epidemiol. 2012;41:961–7. doi: 10.1093/ije/dyr049 21422063

32. Arshad N, Isaksen T, Hansen JB, Brækkan SK. Time trends in incidence rates of venous thromboembolism in a large cohort recruited from the general population. Eur J Epidemiol. 2017;32:299–305. doi: 10.1007/s10654-017-0238-y 28314981

33. Arshad N, Bjori E, Hindberg K, Isaksen T, Hansen JB, Braekkan SK. Recurrence and mortality after first venous thromboembolism in a large population-based cohort. J Thromb Haemost. 2017;15:295–303. doi: 10.1111/jth.13587 27943560

34. Palareti G, Cosmi B, Legnani C, Tosetto A, Brusi C, Iorio A, et al.; PROLONG Investigators. D-dimer testing to determine the duration of anticoagulation therapy. N Engl J Med. 2006;355:1780–9. doi: 10.1056/NEJMoa054444 17065639

35. Franco Moreno AI, García Navarro MJ, Ortiz Sánchez J, Martín Díaz RM, Madroñal Cerezo E, de Ancos Aracil CL, et al. A risk score for prediction of recurrence in patients with unprovoked venous thromboembolism (DAMOVES). Eur J Intern Med. 2016;29:59–64. doi: 10.1016/j.ejim.2015.12.010 26775136

36. Huang W, Goldberg RJ, Anderson FA, Cohen AT, Spencer FA. Occurrence and predictors of recurrence after a first episode of acute venous thromboembolism: population-based Worcester Venous Thromboembolism Study. J Thromb Thrombolysis. 2016;41:525–38. doi: 10.1007/s11239-015-1301-8 26847621

37. Tritschler T, Méan M, Limacher A, Rodondi N, Aujesky D. Predicting recurrence after unprovoked venous thromboembolism: prospective validation of the updated Vienna Prediction Model. Blood. 2015;126:1949–51. doi: 10.1182/blood-2015-04-641225 26341256

38. Altman DG. Prognostic models: a methodological framework and review of models for breast cancer. Cancer Invest 2009;27:235–43. doi: 10.1080/07357900802572110 19291527

39. Peduzzi P, Concato J, Feinstein AR, Holford TR. Importance of events per independent variable in proportional hazards regression analysis. II. Accuracy and precision of regression estimates. J Clin Epidemiol 1995;48:1503–10. doi: 10.1016/0895-4356(95)00048-8 8543964

40. Peduzzi P, Concato J, Kemper E, Holford TR, Feinstein AR. A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol. 1996;49:1373–9. doi: 10.1016/s0895-4356(96)00236-3 8970487

41. Tichelaar V, Mulder A, Kluin-Nelemans H, Meijer K. The acute phase reaction explains only a part of initially elevated factor VIII:C levels: a prospective cohort study in patients with venous thrombosis. Thromb Res. 2012;129:183–6. doi: 10.1016/j.thromres.2011.09.024 21992898

42. O'Donnell J, Mumford AD, Manning RA, Laffan M. Elevation of FVIII:C in venous thromboembolism is persistent and independent of the acute phase response. Thromb Haemost. 2000; 83:10–13. 10669146

43. Klok FA, Hösel V, Clemens A, Yollo WD, Tilke C, Schulman S, et al. Prediction of bleeding events in patients with venous thromboembolism on stable anticoagulation treatment. Eur Respir J. 2016;48:1369–1376. doi: 10.1183/13993003.00280-2016 27471209

44. Klok FA, Barco S, Konstantinides SV. External validation of the VTE-BLEED score for predicting major bleeding in stable anticoagulated patients with venous thromboembolism. Thromb Haemost. 2017;117:1164–1170. doi: 10.1160/TH16-10-0810 28276566

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