Investigation of the Optimal Dose aPCC in Reversing the Effect of Factor Xa Inhibitors—An In Vitro Study

Abstract

Factor (F) Xa inhibitors are safe and effective alternatives to warfarin. There are concerns about the lack of a reversal strategy in case of serious bleeds or need for emergency surgery in situations when the antidote andexanet alfa is not available. Factor concentrates are widely used, but there are few clinical studies regarding the reversal effect of activated prothrombin complex concentrate (aPCC). Because of the feared thrombogenicity, administration of the lowest effective dose would be desirable. To determine the lowest concentration of aPCC sufficient to reverse the effect of rivaroxaban and apixaban. Blood from 18 healthy volunteers were supplemented with apixaban or rivaroxaban. aPCC was added to obtain 10 different concentrations ranging from 0.08-1.60 U/mL. Thromboelastometry and thrombin generation assay were used to assess the reversal effect. aPCC concentrations of 0.08 and 0.16 U/mL restored thromboelastometry clotting time to baseline in apixaban ( P = 1.0) and rivaroxaban ( P = 1.0)-containing samples, respectively. The concentrations 0.08 U/mL ( P = 0.5) and 0.24 U/mL ( P = 0.2) were sufficient to restore thrombin generation. Concentrations of 0.56 U/mL and higher, caused significantly higher ETP than baseline in apixaban-containing samples ( P < 0.05). aPCC concentrations lower than previously reported were effective in reversing the effect of FXa inhibitors in vitro.