Predicting major bleeding during extended anticoagulation for unprovoked or weakly provoked venous thromboembolism.

No clinical prediction model has been specifically developed or validated to identify patients with unprovoked venous thromboembolism (VTE) who are at high risk of major bleeding during extended anticoagulation. In a prospective multinational cohort study of patients with unprovoked VTE receiving extended anticoagulation after completing ≥3 months of initial treatment, we derived a new clinical prediction model using a multivariable Cox regression model based on 22 pre-specified candidate predictors for the primary outcome of major bleeding. This model was then compared with modified versions of five existing clinical scores. A total of 118 major bleeding events occurred in 2516 patients (annual risk, 1.7%; 95% confidence interval, 1.4-2.1). Incidence of major bleeding events per 100 person-years in high- and non-high-risk patients, respectively, were 3.9 (95% confidence interval, 3.0-5.1) and 1.1 (0.8-1.4) using the newly derived CHAP model (creatinine, hemoglobin, age, and use of antiplatelet agent), 3.3 (2.6-4.1) and 1.0 (0.7-1.3) using modified ACCP, 5.3 (0.6-19.2) and 1.7 (1.4-2.0) using modified RIETE, 3.1 (2.3-3.9) and 1.1 (0.9-1.5) using modified VTE-BLEED, 5.2 (3.3-7.8) and 1.5 (1.2-1.8) using modified HAS-BLED, and 4.8 (1.3-12.4) and 1.7 (1.4-2.0) using modified OBRI scores. Modified versions of the ACCP, VTE-BLEED, and HAS-BLED scores help identify patients with unprovoked VTE who are at high risk of major bleeding and should be considered for discontinuation of anticoagulation after 3-6 months of initial treatment. The CHAP model may further improve estimation of bleeding risk by using continuous predictor variables, but external validation is required before its implementation in clinical practice.