Andexanet alfa or prothrombin complex concentrate for acute reversal of oral factor Xa inhibitors: monitoring of antidote effects

Abstract

This study in vitro comprehensively assessed reversal of the anticoagulant effects of rivaroxaban, an oral factor Xa inhibitor, using andexanet alfa and various prothrombin complex concentrate (PCC) products in a battery of tests. In static coagulation assays, andexanet alpha outperformed PCCs except for activated PCC being more effective in standard coagulation times. However, in a flow chamber model mimicking arterial shear, both andexanet alpha and high-concentration PCC restored fibrin formation, but not platelet adhesion. In the Russell's viper venom test and anti-Xa assay, only andexanet alpha could be tested for efficacy. The antidote effects of andexanet alpha and PCCs in restoring coagulation can be qualitatively or selectively demonstrated using in vitro coagulation tests.

Keywords: andexanet alpha; oral factor Xa inhibitor; prothrombin complex concentrate; rivaroxaban; thrombin generation.