Andexanet alfa

Factor Xa inhibitors promote anticoagulation by binding to both free Factor Xa in plasma and Factor Xa attached to the prothrombinase complex. This ultimately leads to the blockade of thrombin generation or clot formation. Andexanet alfa is a factor Xa decoy that binds to factor Xa inhibitors such as apixaban and rivaroxaban with high affinity and prevents them from binding to endogenous factor Xa. It was also shown to sequester factor Xa inhibitors, leading to reversing their anticoagulant effects and restoring the activity of endogenous factor Xa. Andexanet alfa may also achieve procoagulation via binding and inhibiting the activity of Tissue Factor Pathway Inhibitor (TFPI), which is an endogenous inhibitor of Factor Xa. Inhibition of TFPI by andexanet alfa resulted in a transient increase in the level of prothrombin fragments 1 and 2, thrombin-antithrombin complex and D-dimer. Subsequently, this may result in increased tissue factor-initiated thrombin generation. Since it is a genetically modified variant of human factor Xa, andexanet alfa is not able to cleave and activate prothrombin nor assemble into the prothrombinase complex.