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

• Published in: PLOS Medicine
• Main Authors: Timp, Jasmijn F., Braekkan, Sigrid K., Lijfering, Willem M., van Hylckama Vlieg, Astrid, Hansen, John-Bjarne, Rosendaal, Frits R., le Cessie, Saskia, Cannegieter, Suzanne C.
• Format: Text
• Language: English
• Published: Public Library of Science 2019
• Subjects: Research Article; Meier; Norway; Tromsø
• Online Access: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788686/; http://www.ncbi.nlm.nih.gov/pubmed/31603898; https://doi.org/10.1371/journal.pmed.1002883

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, ...