Rivaroxaban and warfarin achieve effective anticoagulation, as assessed by inhibition of TG and in-vivo markers of coagulation activation, in patients with venous thromboembolism

•Thrombin generation was compared for therapeutic rivaroxaban and warfarin•Thrombin generation was lower in rivaroxaban than warfarin patients except for ETP•ETP was greater in rivaroxaban than warfarin treated patients•Only warfarin treated patients with subtherapeutic INR had increased F1.2 and TAT•All rivaroxaban-treated patients had normal markers of in-vivo coagulation activation

IntroductionRivaroxaban is non-inferior to warfarin for the treatment of venous thromboembolism, with regard to clinical efficacy and safety. The ex-vivo effects of warfarin versus therapeutic dose rivaroxaban on in-vivo markers of coagulation activation and thrombin generation remain undefined. The aim of this study was to compare the effects of warfarin and therapeutic dose rivaroxaban on ex-vivo thrombin generation (TG), and the in-vivo markers of coagulation activation, prothrombin fragment 1.2 (F1.2), thrombin-antithrombin complex (TAT), and D-dimer.MethodsEighty-five patients with venous thromboembolism were studied, 45 on warfarin, target INR 2.5 and 40 on rivaroxaban 20 mg once daily.ResultsAnticoagulation was in therapeutic range in 71% (32/45) warfarin and 65% (26/40) rivaroxaban treated patients. 8 patients on warfarin and 9 patients on rivaroxaban had subtherapeutic INR and rivaroxaban levels respectively. Both rivaroxaban and warfarin reduced endogenous thrombin potential (ETP) and peak thrombin, and prolonged lag time and time to peak, compared to normal controls (p < 0.0001). The lag time and time to peak TG were longer, and peak thrombin was lower in patients receiving rivaroxaban (p < 0.0001) compared with warfarin, although warfarin-treated patients had lower ETP (p = 0.0008). In-vivo coagulation activation markers were within the normal ranges in all rivaroxaban-treated patients (including those with levels considered to be subtherapeutic) and in 37/45 warfarin-treated patients who had an INR ≥ 2.0. The warfarin-treated patients with subtherapeutic INRs exhibited slightly raised F1.2 and/or TAT.ConclusionIn conclusion, both rivaroxaban and warfarin provided effective anticoagulation, as assessed by inhibition of TG and makers of in-vivo coagulation activation.