Effects of rivaroxaban and dabigatran on global hemostasis in patients with atrial fibrillation

Abstract

The study was aimed to evaluate the effects of two standard doses of rivaroxaban and dabigatran on global hemostatic assays in patients with atrial fibrillation. The study included 52 patients treated with rivaroxaban (15/20 mg), 50 on dabigatran (110/150 mg) and 20 healthy individuals. Platelet-poor plasma was used for determination of three global hemostatic assays, namely endogenous thrombin potential (ETP), calibrated automated thrombogram (CAT) and overall hemostasis potential (OHP). Rivaroxaban and dabigatran reduced ETP (P lt 0.01) although OHP (P lt 0.05) was diminished only by dabigatran. Strong correlations were noticed between ETP parameters and the plasma concentrations of rivaroxaban (ETP, rUS0.51; c-max, rUS0.85; t-lag, rU0.83; t-max, rU0.66) as well as with plasma concentration of dabigatran (ETP, rUS0.75; c-max, rUS0.74; t-lag, rU0.73; t-max, rU0.52). Analysis of dabigatran concentrations under 50 ng/ml showed that ETP parameter has area under the concentration-time curvereceiver operating characteristic value of 0.879 (95% confidence interval 0.776-0.980). Dabigatran treatment paradoxically increased area under the concentration-time curve and peak values although rivaroxaban decreased peak values (P lt 0.01). However, significant correlation between CAT parameters and plasma concentration of both direct oral anticoagulants was not observed. We confirmed that the CAT assay is inappropriate for estimation of dabigatran effects and is not fully sensitive as regards rivaroxaban. The ETP assay can potentially be the appropriate method for estimation of global hemostatic capacity as regards both direct oral anticoagulants. The role of OHP needs to be confirmed in additional studies. ETP parameter of chromogenic assay has promising potential in exclusion of high plasma concentrations of dabigatran.