What is Andexanet Alfa (andexanet alfa), a recombinant factor Xa inhibitor antidote?

From the Guidelines

Andexanet alfa is a recombinant factor Xa inhibitor antidote that rapidly reverses anticoagulation in patients treated with oral FXaIs, such as apixaban and rivaroxaban, by decreasing anti-FXa activity and increasing thrombin generation. According to the most recent study published in the Journal of Thrombosis and Haemostasis in 2024 1, andexanet alfa is a recombinant FXa variant that works by binding to factor Xa inhibitors in the blood, preventing them from inhibiting natural factor Xa, and thus restoring normal coagulation.

Key Characteristics of Andexanet Alfa

• It is administered intravenously, with dosing based on the specific factor Xa inhibitor and when it was last taken
• The medication has been shown to rapidly decrease anti-FXa activity and increase thrombin generation in individuals treated with oral FXaIs 1
• In clinical trials, andexanet alfa significantly reduced anti-FXa activity for up to 4 hours and increased thrombin generation for up to 12 hours 1

Clinical Use and Efficacy

• Andexanet alfa was approved by the US Food and Drug Administration in 2019 for the reversal of anticoagulation in patients treated with oral FXaIs 1
• The ANNEXA-4 study demonstrated that andexanet alfa was effective in treating major bleeding in patients receiving FXaIs, with a median anti-FXa activity decrease of 93% and 80% of evaluable participants achieving excellent or good hemostatic efficacy at 12 hours 1
• However, thrombotic events occurred in 10% of participants, highlighting the need for careful monitoring and use in appropriate clinical settings 1

Important Considerations

• Andexanet alfa should only be used in emergency situations to reverse anticoagulation in patients experiencing life-threatening or uncontrolled bleeding
• The medication carries significant cost and potential risks, including infusion reactions, thromboembolic events, and ischemic events
• Therefore, andexanet alfa should be used with caution and only in clinical settings where the benefits outweigh the risks, as supported by the most recent evidence 1

From the FDA Drug Label

ANDEXXA (coagulation factor Xa (recombinant), inactivated-zhzo) is a recombinant modified human factor Xa (FXa) protein The active ingredient in ANDEXXA is a genetically modified variant of human FXa. The active site serine was substituted with alanine, rendering the molecule unable to cleave and activate prothrombin The gamma-carboxyglutamic acid (Gla) domain was removed to eliminate the protein's ability to assemble into the prothrombinase complex, thus removing the potential anticoagulant effects.

Andexanet alfa is a recombinant factor Xa inhibitor antidote, a genetically modified variant of human factor Xa, indicated for patients treated with rivaroxaban or apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding 2, 2, 2.

• Key characteristics: recombinant modified human factor Xa protein, inactive site serine, removed Gla domain.
• Indication: reversal of anticoagulation in patients treated with rivaroxaban or apixaban due to life-threatening or uncontrolled bleeding.

From the Research

Overview of Andexanet Alfa

• Andexanet alfa is a recombinant modified human factor Xa protein that acts as a decoy to bind factor Xa inhibitors, thereby reversing the anticoagulant effects of factor Xa inhibitors 3, 4, 5.
• It is currently approved for use in patients treated with rivaroxaban and apixaban who have life-threatening or uncontrolled bleeding 3, 4, 5, 6.

Mechanism of Action

• Andexanet alfa competes with endogenous factor Xa to bind factor Xa inhibitors, restoring the activity of endogenous factor Xa 5.
• It reduces anti-factor Xa levels, with reduced levels being maintained during continued treatment 5.

Efficacy and Safety

• Andexanet alfa has been shown to be effective in reversing the anticoagulant effect of apixaban and rivaroxaban in patients with major bleeding 4, 6.
• The safety profile of andexanet alfa is generally similar to that of other approved anticoagulation reversal agents, but it carries a risk of thrombotic events 4, 5, 6.
• A study comparing andexanet alfa to four-factor prothrombin complex concentrate found that andexanet alfa was associated with greater odds of achieving hemostatic effectiveness and decreased odds of mortality 7.

Clinical Use

• Andexanet alfa is administered as a bolus followed by a 120-minute continuous infusion 4.
• It is recommended that anticoagulant therapy be resumed as soon as medically appropriate after treatment with andexanet alfa to minimize the risk of thrombotic events 5.
• The use of andexanet alfa in clinical practice should be guided by international guidelines and well-designed studies comparing its efficacy and safety to other reversal strategies 6.