What is the recommended approach for reversing anticoagulation in a patient taking Eliquis (apixaban) with impaired renal function who presents with life-threatening bleeding?

Reversal of Apixaban (Eliquis) in Life-Threatening Bleeding with Renal Impairment

Administer andexanet alfa immediately as the first-line specific reversal agent for life-threatening bleeding in patients with impaired renal function taking apixaban. 1, 2

Immediate Reversal Strategy

Andexanet alfa is the preferred reversal agent, achieving >90% reduction in anti-factor Xa activity within 2 minutes of administration and demonstrating hemostatic efficacy in 82% of patients at 12 hours. 1

Andexanet Alfa Dosing

The dosing regimen depends on the timing and amount of the last apixaban dose: 2

• Low dose regimen: For apixaban ≤5 mg or last dose >8 hours ago

  • IV bolus: 400 mg at 30 mg/min
  • Continuous infusion: 4 mg/min for up to 120 minutes

• High dose regimen: For apixaban >5 mg or unknown dose taken within 8 hours

  • IV bolus: 800 mg at 30 mg/min
  • Continuous infusion: 8 mg/min for up to 120 minutes

Administration Protocol

• Start the bolus within 2 minutes at approximately 30 mg/min 2
• Immediately follow with continuous IV infusion for up to 120 minutes 2
• Use a 0.2 or 0.22 micron in-line polyethersulfone filter 2

Why Renal Impairment Matters

Impaired renal function is a specific indication for considering reversal because apixaban clearance is significantly prolonged when creatinine clearance is <30 mL/min, with approximately 25% of apixaban undergoing renal elimination. 3, 1 The half-life extends substantially in severe renal dysfunction, making drug accumulation and prolonged anticoagulant effect more likely. 3

Alternative Reversal Options

If andexanet alfa is unavailable, administer four-factor prothrombin complex concentrate (4F-PCC) at 25-50 units/kg as an alternative, though evidence is less robust. 3, 1

• Start with 25 units/kg and repeat if necessary given thrombotic potential 3
• 4F-PCC has demonstrated reversal of apixaban's effects on endogenous thrombin potential and other coagulation parameters in controlled studies 4
• Do not use fresh frozen plasma (FFP) as there is no human study evidence supporting FFP for DOAC reversal, and it is unlikely to be effective against direct factor Xa inhibition 3

Adjunctive Measures

Activated Charcoal

• Consider activated charcoal only if the last apixaban dose was within 2-4 hours 3, 1
• Most DOACs reach peak plasma concentration within 3 hours, though efficacy has not been evaluated in clinical practice 3

What NOT to Do

• Do not use vitamin K - it is ineffective for DOACs as they are not vitamin K antagonists 3
• Do not use platelet transfusion or desmopressin - no clinical or laboratory evidence supports this practice, and platelet transfusion may increase mortality 3
• Do not attempt dialysis - apixaban has high protein binding (87%) and is not dialyzable 3

Laboratory Monitoring Considerations

• Standard coagulation tests (PT, aPTT) are unreliable for assessing apixaban levels and should not guide management decisions 3
• Specific anti-factor Xa assays are optimal but not routinely available and should not delay treatment 3
• Monitor serial hemoglobin levels to detect ongoing occult bleeding 1
• Assess creatinine for renal function evaluation 1

Critical Safety Warnings

Andexanet alfa carries significant thrombotic risks, including: 1, 2

• Arterial and venous thromboembolic events
• Ischemic events (myocardial infarction and stroke)
• Cardiac arrest and sudden death

Monitor for thromboembolic events and resume anticoagulation when medically appropriate after bleeding control is achieved, as prompt resumption significantly reduces thrombotic risk. 1, 2

Definition of Life-Threatening Bleeding

Andexanet alfa is specifically indicated for: 1

• Intracranial hemorrhage
• Symptomatic or expanding extradural hemorrhage
• Uncontrollable hemorrhage with hemodynamic instability

Common Pitfalls to Avoid

• Do not delay reversal waiting for laboratory confirmation - clinical presentation should drive decision-making 3
• Do not use PCC as first-line when andexanet alfa is available - andexanet alfa is the FDA-approved specific reversal agent 3, 1, 2
• Do not forget that renal impairment prolongs apixaban effect - this population requires more aggressive reversal consideration 3, 1
• Do not overlook thrombotic risk after reversal - plan for anticoagulation resumption timing 1, 2