How do you reverse Eliquis (apixaban) in a patient with bleeding complications or requiring emergency surgery?

Reversal of Eliquis (Apixaban)

For life-threatening bleeding or emergency surgery in patients on Eliquis, administer andexanet alfa immediately as the first-line specific reversal agent, using dosing based on the timing and amount of the last apixaban dose. 1, 2, 3

Indications for Reversal

Reversal is warranted in the following situations:

• Life-threatening bleeding: Intracranial hemorrhage, symptomatic or expanding extradural hemorrhage, or uncontrollable hemorrhage 1
• Bleeding in critical organs or closed spaces: Intraspinal, intraocular, pericardial, pulmonary, retroperitoneal, or intramuscular with compartment syndrome 1, 3
• Persistent major bleeding despite local hemostatic measures or high risk of recurrent bleeding due to delayed drug clearance or overdose 1
• Emergency surgery with high bleeding risk: Neurosurgery (intracranial, extradural, or spinal), lumbar puncture, cardiac or vascular surgery, or major organ surgery 1

Do NOT use reversal agents for: elective surgery, gastrointestinal bleeds responding to supportive measures, high drug levels without bleeding, or procedures that can be delayed ≥8 hours for drug clearance 1

Primary Reversal Strategy: Andexanet Alfa

Andexanet alfa is the FDA-approved specific reversal agent for apixaban and should be administered without waiting for laboratory confirmation in life-threatening situations. 1, 4

Dosing Regimen

The dosing depends on the last apixaban dose and timing:

• Low-dose regimen: 400 mg IV bolus over 15-30 minutes, followed by 480 mg continuous infusion at 4 mg/min for 2 hours 1, 2

  • Use for patients who received ≤5 mg apixaban OR last dose was ≥8 hours prior 2

• High-dose regimen: 800 mg IV bolus over 15-30 minutes, followed by 960 mg continuous infusion at 8 mg/min for 2 hours 1, 2

  • Use for patients who received >5 mg apixaban OR last dose was <8 hours prior OR timing unknown 1, 2

Efficacy and Mechanism

• Andexanet alfa reduces anti-factor Xa activity by 92-93% within 2 minutes of bolus administration 2, 5
• Achieves excellent or good hemostasis in 78-82% of patients at 12 hours 5, 3
• Acts as a recombinant modified factor Xa decoy protein that binds and sequesters apixaban 1, 2

Alternative Reversal Options

When andexanet alfa is unavailable, use four-factor prothrombin complex concentrate (4F-PCC) as an alternative, though it is less effective than andexanet alfa. 1, 2, 3

4F-PCC Dosing

• 50 units/kg IV (maximum 5000 units) or 2000 units fixed dose 1, 2
• Additional 25 units/kg may be given if clinically needed 1
• Onset of action within 10 minutes, duration approximately 8 hours 1

Activated PCC (aPCC) at 50 units/kg can also be considered, with clinical hemostasis achieved in approximately 69% of patients, though evidence is limited. 1, 6

Laboratory Assessment

Do not delay reversal for laboratory results in life-threatening bleeding. 1

When available, consider:

• Anti-factor Xa activity assay is the preferred test for quantifying apixaban levels 2, 3
• Drug concentration >50 ng/mL is clinically significant for serious bleeding and warrants antidote administration 1, 3
• For urgent surgery, consider reversal if drug concentration >30 ng/mL 1
• Assess renal function (creatinine clearance) to estimate drug half-life and clearance 1, 5

Drug Clearance Considerations

• Normal renal function (CrCl >60 mL/min): Apixaban half-life ≤12 hours; reversal unlikely needed if last dose was >24 hours ago 1
• Moderate renal impairment (CrCl 30-50 mL/min): Drug clearance delayed 36-48 hours 1
• **Severe renal impairment (CrCl <30 mL/min):** Drug clearance >48 hours; reversal more critical in this population 1, 5

Supportive Measures

In addition to specific reversal agents, implement:

• Discontinue apixaban immediately in patients with active pathological hemorrhage 4
• Mechanical compression and local hemostatic measures 1
• Red blood cell transfusion to maintain hemoglobin >7-8 g/dL 1
• Platelet transfusion if thrombocytopenia <60 × 10⁹/L or thrombopathy present 1
• Tranexamic acid 1 g IV (repeat every 6 hours if necessary) as adjuvant therapy 1
• Activated charcoal if apixaban was ingested within 2-6 hours (reduces absorption by 27-50%) 4

Do NOT use: Vitamin K, protamine sulfate, fresh frozen plasma as reversal agents—they are ineffective for apixaban. 1, 4

Critical Safety Warnings

Thrombotic Risk After Reversal

• Thrombotic events occur in 10-18% of patients within 30 days after andexanet alfa administration 2, 5
• Events include arterial and venous thromboembolism, myocardial infarction, stroke, cardiac arrest, and sudden death 5
• Resume anticoagulation as soon as hemostasis is achieved to reduce thrombotic risk 5, 3
• Consider bridging with prophylactic low-molecular-weight heparin if anticoagulation must be delayed 2

Duration of Reversal Effect

• Andexanet alfa effect lasts approximately 2 hours after infusion stops 1, 3
• Apixaban anticoagulant effect persists for at least 24 hours (approximately two half-lives) after the last dose 4
• Significant apixaban concentrations may reappear after reversal, contributing to recurrent bleeding 1
• Continued clinical and laboratory monitoring is essential after reversal 1

Common Pitfalls to Avoid

• Do not wait for coagulation test results before administering reversal in life-threatening bleeding 1
• PT, INR, and aPTT are not useful for monitoring apixaban anticoagulation effect and should not guide reversal decisions 1, 4
• Hemodialysis is ineffective for removing apixaban 4
• Do not use desmopressin or antifibrinolytic agents alone—no clinical experience supports their effectiveness for apixaban reversal 4
• Avoid reversal for elective procedures—delay surgery ≥8 hours when possible to allow natural drug clearance 1