Clinical outcomes and plasma clot permeability and lysability in patients with venous thromboembolism on rivaroxaban : a cohort study

Denser fibrin structure and impaired fibrinolysis reported in patients following venous thromboembolism (VTE) can predict recurrent VTE after cessation of anticoagulation. The aim of the study was to investigate whether the properties of fibrin clot may be useful in predicting adverse events in patients with VTE receiving rivaroxaban. In 132 patients with VTE treated with rivaroxaban for 8 weeks or longer, we determined plasma clot permeability ($K_{s}$) and clot lysis time (CLT) in blood samples collected 2 to 28 hours after rivaroxaban intake (20 mg/d). The primary endpoint was a composite of major and clinically relevant nonmajor bleeding, while the secondary endpoint was recurrent symptomatic VTE. During a median follow‑up of 32 months, the annual rates of primary and secondary endpoints were 3.6% and 2.7%, respectively. There were no differences in $K_{s}$ and CLT between individuals who experienced the primary endpoint and the remainder. Patients with recurrent VTE had lower baseline $K_{s}$ (-26.7%) and prolonged CLT (+20.8%) on rivaroxaban, without differences in rivaroxaban concentrations at the time of blood collection. After adjustment for confounding factors, $K_{s}$ was the only predictor of VTE recurrence on rivaroxaban (odds ratio, 0.23; 95% CI, 0.06-0.94). Our study suggests that $K_{s}$ assessed on rivaroxaban may provide prognostic information about the risk of recurrent VTE in anticoagulated patients.