Reversing the action of newer oral anticoagulants

Abstract

We appreciate the remarks of Dr. Fagan and colleagues. As stated in our review, while the studies on the reversal of factor Xa inhibitors were conducted in animal models and healthy volunteers, and the effects of such prohemostatic agents were evaluated with surrogate markers,1–8 the best option in the setting of hemorrhage is unknown. Presently, no published studies have addressed the use of prohemostatic agents in patients with hemorrhage. Likewise, no comparative or combination-treatment trials are available. Recently, Marlu et al.9 used thrombin-generation tests to assess the effect of four-factor prothrombin complex concentrate (PCC), activated PCC (aPCC), and recombinant factor VIIa (rFVIIa) on the anticoagulant effect of rivaroxaban. In this ex vivo study, 10 healthy white male participants received one oral dose of rivaroxaban 20 mg. Blood samples were taken before and two hours after rivaroxaban administration. The anticoagulant-reversal effects of the prohemostatic agents were investigated in vitro at dose-ranging concentrations. Rivaroxaban significantly prolonged pro-thrombin time, reduced the quantitative parameters of thrombin peak and endogenous thrombin potential (ETP), and increased the pharmacokinetic measures of lag time (LT) and time to reach the maximum concentration of thrombin (TTP).