High rate of unprovoked recurrent venous thrombosis is associated with high thrombin-generating potential in a prospective cohort study

Objective: To determine the predictive value of measurement of parameters of thrombin generation for unprovoked recurrent venous thrombosis. Methods: Measurements were made of thrombin generation in a prospective cohort study of 188 patients with a first episode of venous thrombosis that was unprovoked, or provoked by a non-surgical trigger. Results: The endogenous thrombin potential (ETP) was the only parameter associated with unprovoked recurrent thrombosis in a multivariate model [hazard ratio (HR) 1.3 per 100 nmol L min(-1) increase, 95% confidence interval (CI) 1.0-1.6]. Patients with a high ETP had a significantly higher rate of unprovoked recurrence than those with a low ETP (HR 2.9, 95% CI 1.3-6.6, cumulative recurrence at 4 years 27% vs. 11%). Patients with an unprovoked first event had a significantly higher rate of unprovoked recurrence than those with a provoking factor (HR 2.7, 95% CI 1.2-6.1), and in these patients there was a significantly higher rate of unprovoked recurrence in association with a high ETP (HR 4.0, 95% CI 1.3-11.8). After adjustment for D-dimer, thrombophilia, sex, and whether or not the first event was unprovoked, a high ETP remained a significant predictor of recurrence (HR 2.6, 95% CI 1.2-6.0). Conclusions: This study demonstrates a high rate of unprovoked recurrent venous thrombosis in patients presenting with a first episode of venous thrombosis and a high ETP.