What is the best initial therapeutic management to reverse anticoagulation in a patient on rivaroxaban (Xarelto) with a history of atrial fibrillation after a fall?

Andexanet Alfa (Andexxa) for Rivaroxaban Reversal in Intracranial Hemorrhage

Administer andexanet alfa immediately for this patient with presumed intracranial hemorrhage on rivaroxaban—this is the only FDA-approved specific reversal agent for rivaroxaban and should be given without delay in life-threatening bleeding. 1

Rationale for Andexanet Alfa as First-Line Therapy

• Andexanet alfa is the specific reversal agent for rivaroxaban, acting as a modified recombinant factor Xa that binds factor Xa inhibitors with high affinity, rapidly reversing anticoagulation within minutes. 1

• The 2020 ACC Expert Consensus Decision Pathway explicitly recommends andexanet alfa as first-line therapy for patients on rivaroxaban or apixaban presenting with major bleeding, including intracranial hemorrhage. 1

• Andexanet reduces anti-factor Xa activity by 92% for rivaroxaban, with effects occurring within 2-5 minutes of administration and sustained throughout the infusion period. 1, 2

• In the ANNEXA-4 trial, 79% of patients achieved effective hemostasis at 12 hours after andexanet administration for major bleeding events. 1

Dosing Algorithm for This Patient

High-dose regimen is indicated for rivaroxaban reversal in this emergent scenario: 1

• 800 mg IV bolus administered at 30 mg/min, followed by
• 960 mg continuous infusion at 8 mg/min for up to 120 minutes

Use high-dose if: 1

• Last rivaroxaban dose >10 mg was taken <8 hours prior
• Timing of last dose is unknown (as may be the case here)
• Any dose taken <8 hours prior in life-threatening bleeding

Critical Management Points

• Do not delay andexanet administration for laboratory confirmation of rivaroxaban levels in life-threatening bleeding situations like intracranial hemorrhage. 3

• The reversal effect is transient—anti-factor Xa activity returns toward baseline approximately 2 hours after completing the infusion, so definitive bleeding control measures must be implemented during this window. 1, 3

• Thrombotic events occurred in 18% of patients within 30 days in ANNEXA-4, highlighting the need for careful consideration of anticoagulation resumption timing once hemostasis is achieved. 1

Why Other Options Are Inferior

Fresh frozen plasma (Option B) is not appropriate because:

• FFP requires large volumes (15-30 mL/kg) for adequate factor replacement, risking volume overload in this intubated patient. 1
• FFP has not been studied for DOAC reversal and lacks specific anti-factor Xa reversal properties. 1

Platelet transfusion (Option C) has no role because:

• Rivaroxaban is a factor Xa inhibitor, not an antiplatelet agent—platelets will not reverse its anticoagulant effect. 1

Vitamin K (Option D) is ineffective because:

• Rivaroxaban is a direct oral anticoagulant that does not work through vitamin K-dependent pathways like warfarin does. 1, 4
• Vitamin K only reverses warfarin and other vitamin K antagonists. 1

Alternative if Andexanet Unavailable

If andexanet alfa is not available, administer four-factor prothrombin complex concentrate (4F-PCC) at 50 units/kg (maximum 5000 units) or activated PCC, though these are less effective and not specifically studied for rivaroxaban reversal. 1, 3

Additional Supportive Measures

• Consider activated charcoal 50g if rivaroxaban ingestion occurred within 2-4 hours, though this is unlikely given the emergent presentation. 1

• Rivaroxaban is not dialyzable due to high plasma protein binding (>90%), so hemodialysis has no role. 4

• Neurosurgical consultation should occur simultaneously with reversal agent administration for potential surgical intervention. 3