An elderly patient on apixaban (factor Xa inhibitor) with normal renal function presents with decreased mental status and left arm and leg weakness, what is the most appropriate next step in management?

Immediate Reversal with Prothrombin Complex Concentrate (Kcentra)

This elderly patient presenting with acute intracranial hemorrhage (ICH) while on apixaban requires immediate reversal with 4-factor prothrombin complex concentrate (PCC/Kcentra) at 50 U/kg (maximum 4,000 units) if andexanet alfa is unavailable. 1, 2

First-Line Reversal Strategy

• Andexanet alfa is the FDA-approved specific reversal agent for apixaban-associated life-threatening bleeding, including intracranial hemorrhage 1, 3
• For apixaban taken within 8 hours (as in this case with 4 hours since last dose), administer the high-dose regimen: 800 mg IV bolus over 30 minutes followed by 960 mg infusion over 2 hours 3
• Andexanet alfa reduced anti-factor Xa activity by 92% in the ANNEXA-4 trial, with 79% of ICH patients achieving excellent or good hemostatic outcomes 1

Alternative When Andexanet Alfa Unavailable

• When andexanet alfa is not available, 4-factor PCC (Kcentra) should be administered at 50 U/kg (maximum 4,000 units) 1, 2
• This recommendation is based on the 2020 ACC Expert Consensus and 2022 AHA/ASA ICH guidelines 1
• PCC provides hemostatic effectiveness in apixaban-associated bleeding, though it is not a specific reversal agent 4

Why Other Options Are Incorrect

• Idarucizumab (Option A) is specific for dabigatran reversal only, not factor Xa inhibitors like apixaban 1
• Protamine (Option B) reverses heparin, not oral factor Xa inhibitors 1
• Recombinant factor VIIa (Option D) is not recommended as a first-line reversal agent for apixaban-associated bleeding 1

Critical Clinical Context

• The patient's decreased mental status and focal neurological deficits (left arm and leg weakness) strongly suggest acute intracranial hemorrhage, which constitutes life-threatening bleeding requiring immediate reversal 1
• Normal renal function is favorable as apixaban has 27% renal clearance, meaning the drug effect will diminish within 24-48 hours after the last dose 1, 5
• The 4-hour window since last apixaban dose places the patient near peak drug levels (Tmax 3-4 hours), making immediate reversal critical 1

Administration Protocol

• Administer PCC at 50 U/kg IV immediately while arranging neuroimaging and neurosurgical consultation 2
• Monitor for thromboembolic complications, which occur in approximately 10% of patients receiving reversal agents 1, 2
• Do not delay reversal for laboratory confirmation of apixaban levels, as clinical presentation of ICH warrants immediate action 1

Important Caveats

• Reversal agents increase thrombotic risk (10.3% with andexanet alfa vs 5.6% baseline), so they should only be used for life-threatening bleeding 1, 6
• PCC does not specifically reverse factor Xa inhibitors but provides hemostatic factors to support clot formation 1, 4
• Avoid restarting apixaban until adequate hemostasis is achieved and the acute bleeding risk has resolved, typically requiring neurosurgical input for ICH 6