andexanet alfa

Andexanet alfa is a recombinant, catalytically inactive form of human factor Xa that acts as a decoy molecule. It binds direct factor Xa inhibitors (apixaban, rivaroxaban, and off-label edoxaban) with high affinity, sequestering them in the plasma and preventing their inhibitory action on endogenous factor Xa. This restores factor Xa activity and thrombin generation, thereby reversing the anticoagulant effect. It does not have significant catalytic activity itself, avoiding direct procoagulant effects, though it can transiently inhibit tissue factor pathway inhibitor (TFPI), which may contribute to a prothrombotic rebound effect. Clinically, it is indicated for reversal of anticoagulation in patients experiencing life-threatening or uncontrolled bleeding while on factor Xa inhibitors, such as intracranial hemorrhage or major GI bleeding. Dosing is weight- and drug-based (low vs. high dose bolus followed by infusion). A key safety concern is an increased risk of thrombotic events post-administration, thought to be related to transient TFPI inhibition and rebound anticoagulant factor activity after drug clearance; patients should be monitored for thromboembolic complications and anticoagulation often needs to be restarted promptly once hemostasis is achieved. Unlike idarucizumab (used for dabigatran reversal) and protamine (for heparin), andexanet is specific to factor Xa inhibitors and does not work for warfarin or unfractionated/low molecular weight heparin reversal. Monitoring of reversal is clinical rather than via specific lab assays, as anti-Xa levels can be falsely altered by the drug’s presence.