Background: Increased thrombin generation is associated with an increased risk of recurrent venous thromboembolism. We investigated the relation between endogenous thrombin potential (ETP) and risk of recurrent venous thromboembolism and evaluated whether prediction of recurrence can be improved by a combined analysis of ETP and D-dimer.
Methods: We followed 861 patients with first spontaneous venous thromboembolism and determined ETP and D-dimer after discontinuation of anticoagulation. Patients with natural inhibitor deficiency, lupus anticoagulant, or cancer were excluded. The study endpoint was symptomatic recurrent venous thromboembolism.
Results: One hundred thirty patients (15.1%) had recurrence. High ETP (> or = 100%) conferred a 1.6-fold increased risk of recurrence (95% CI 1.1-2.3) after adjustment for age, sex, factor V Leiden, factor II G20210A, and duration of anticoagulation. After adjustment for D-dimer, risk of recurrence remained significantly higher among patients with high ETP [hazard ratio 1.6 (95% CI 1.01-2.4)]. After adjustment for ETP, high D-dimer (> or = 0.5 mg/L) conferred a 1.8-fold (95% CI 1.1-2.8) increased risk of recurrence. Compared with patients with low ETP and low D-dimer, risk of recurrence was 2.8-fold (95% CI 1.5-5.3) higher among patients with both high ETP and high D-dimer after adjustment for potential confounders.
Conclusions: ETP and D-dimer are independent predictors of recurrent venous thromboembolism. Assessing risk of recurrence can be optimized by combining these indicators of thrombin generation.