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: 10.1371/journal.pmed.1002883



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.


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


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