Andexanet alfa. Andexanet alfa is a recombinant human factor Xa (FXa) decoy protein that lacks procoagulant activity. A mutation in the serine residue of the active site disrupts the catalytic domain, preventing it from cleaving prothrombin and thereby generating thrombin. Andexanet alfa binds binds FXa inhibitors with high affinity and a 1:1 stoichiometric ratio, leading to the release of endogenous FXa to resume its normal function in hemostasis. In addition to the mutation in the active site serine residue, a mutation has been introduced that prevents the decoy protein from binding to membranes via the carboxyglutamic acid (Gla) domain. The Gla domain mediates binding of FXa to phospholipids, where the prothrombinase complex is assembled. The absence of the membrane-binding Gla-domain prevents andexanet alfa, when bound to FXa inhibitors, from competing with FXa for incorporation into the prothrombinase complex.
