Reversing the Anticoagulant Effects of Factor Xa Inhibitors

Andexanet alfa has provisional approval for the reversal of anticoagulation in adult patients who experience life-threatening or uncontrolled bleeding with a direct factor Xa inhibitor (apixaban or rivaroxaban).

Andexanet alfa is a recombinant form of the human factor Xa protein. While its primary mechanism of action is to bind and sequester factor Xa inhibitors, it also inhibits the activity of tissue factor pathway inhibitor (TFPI). Andexanet alfa has no anticoagulant effect of its own, as the protein has been modified to remove the enzymatic activity of factor Xa.

Andexanet alfa is administered as an initial intravenous bolus followed by an intravenous infusion. The recommended dose depends upon the dose of apixaban or rivaroxaban and the time since the last dose of the anticoagulant. It is not recommended to use andexanet alfa if more than 18 hours have passed since the last dose of apixaban or rivaroxaban.

The single-arm ANNEXA-4 trial investigated the efficacy of andexanet alfa in patients with acute major bleeding within 18 hours of receiving a factor Xa inhibitor. The co-primary outcomes were change in anti-factor Xa activity and the proportion of patients with good or excellent haemostatic efficacy 12 hours after the completion of the infusion. In patients who had received apixaban or rivaroxaban, andexanet alfa resulted in a 92% reduction in anti-factor Xa activity at the end of the bolus administration. Good or excellent haemostatic efficacy at 12 hours was achieved in 82% of patients (80% in patients presenting with intracranial bleeding and 85% for gastrointestinal bleeding).

Following the reversal of factor Xa inhibitor therapy, patients are at risk of thromboembolic events associated with their underlying disease state. Therefore, consideration should be given to restarting anticoagulant therapy as soon as is appropriate.