Comparison of three‐factor and four‐factor prothrombin complex concentrates regarding reversal of the anticoagulant effects of rivaroxaban in healthy volunteers

Abstract

Four-factor prothrombin complex concentrates (PCCs), which contain factorII, FVII, FIX, and FX, have shown the potential to reverse the anticoagulant effect of rivaroxaban in healthy volunteers. The purpose of this study was to determine whether a three-factor PCC, which contains little FVII, has a similar effect. We performed an open-label, single-center, parallel-group study comparing the effect of a three-factor PCC (ProfilnineSD) with that of a four-factor PCC (BeriplexP/N) on the pharmacodynamics of rivaroxaban in 35 healthy volunteers. After receiving 4days of rivaroxaban 20mg twice daily to obtain supratherapeutic steady-state concentrations, volunteers were randomized to receive a single 50IUkg(-1) bolus dose of four-factor PCC, three-factor PCC or saline 4h after the morning dose of rivaroxaban on day5, and the effects of these interventions on prothrombin time and thrombin generation were determined. Within 30min, four-factor PCC reduced mean prothrombin time by 2.5-3.5s, whereas three-factor PCC produced only a 0.6-1.0-s reduction. In contrast, three-factor PCC reversed rivaroxaban-induced changes in thrombin generation more than four-factor PCC. This study demonstrates the potential of both three-factor and four-factor PCCs to at least partially reverse the anticoagulant effects of rivaroxaban in healthy adults. The discrepant effects of the PCC preparations may reflect differences in the procoagulant components present in each.