Plasma clot permeability and lysability determined on rivaroxaban and clinical outcomes in patients with venous thromboembolism: a cohort study

INTRODUCTION: Denser fibrin structure and impaired fibrinolysis reported in patients following venous thromboembolism (VTE) can predict recurrent VTE after cessation of anticoagulation. OBJECTIVES: 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. PATIENTS AND METHODS: In 132 patients with VTE treated with rivaroxaban for 8 weeks or longer, we determined plasma clot permeability (Ks) 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. RESULTS: 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 Ks and CLT between individuals who experienced the primary endpoint and the remainder. Patients with recurrent VTE had lower baseline Ks (-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, Ks was the only predictor of VTE recurrence on rivaroxaban (odds ratio, 0.23; 95% CI, 0.06-0.94). CONCLUSIONS: Our study suggests that Ks assessed on rivaroxaban may provide prognostic information about the risk of recurrent VTE in anticoagulated patients.