How long should Eliquis (apixaban) be held in cases of suspected bleeding?

Management of Suspected Bleeding on Eliquis (Apixaban)

For suspected bleeding on apixaban, immediately discontinue the medication and do not restart until adequate hemostasis is established; the drug effect will dissipate based on renal function, with a half-life of 6-15 hours in patients with normal kidney function. 1

Immediate Actions

• Stop apixaban immediately upon suspicion of bleeding—do not wait for confirmation 2
• The duration to hold depends on bleeding severity and renal function, not a fixed time period 1
• For non-life-threatening bleeding, supportive care alone may be sufficient as apixaban has a relatively short half-life (6-15 hours with normal renal function) 1, 3

Drug Clearance Timeline Based on Renal Function

The time for apixaban to clear from the system varies significantly with kidney function 1:

• CrCl ≥80 mL/min: Half-life approximately 6-15 hours 1
• CrCl 50-79 mL/min: Half-life approximately 6-15 hours 1
• CrCl 30-49 mL/min: Half-life approximately 6-15 hours 1
• CrCl 15-29 mL/min: Half-life approximately 6-15 hours 1
• CrCl <15 mL/min (off dialysis): Half-life approximately 17 hours 1

Most patients will have minimal drug effect after 24-48 hours (approximately 2-3 half-lives), though complete clearance requires 48-72 hours in those with normal renal function 1, 3

Management of Life-Threatening or Major Bleeding

For major bleeding with hemodynamic instability or intracranial hemorrhage, active reversal is indicated 1:

• First-line: Administer andexanet alfa (FDA-approved specific reversal agent) 1, 3

  • Low-dose regimen: 400 mg IV bolus followed by 4 mg/min infusion for 120 minutes if last apixaban dose ≤5 mg taken <8 hours prior, or timing unknown 1
  • High-dose regimen: 800 mg IV bolus followed by 8 mg/min infusion for 120 minutes if last apixaban dose >5 mg taken <8 hours prior, or timing unknown 1

• If andexanet alfa unavailable: Administer four-factor prothrombin complex concentrate (4F-PCC) or activated PCC 1, 3

• Consider activated charcoal if apixaban was ingested within 2-4 hours (though most bleeding presents later) 1

When to Resume Apixaban

Restart apixaban only after adequate hemostasis has been established—there is no fixed time interval 2:

• The FDA label explicitly states: "Apixaban tablets should be restarted after the surgical or other procedures as soon as adequate hemostasis has been established" 2
• This requires clinical judgment based on bleeding site, severity, and underlying thrombotic risk 1
• For procedures, the FDA recommends holding apixaban at least 48 hours before moderate-to-high bleeding risk interventions and at least 24 hours before low bleeding risk procedures 2

Critical Pitfalls to Avoid

• Do not use platelet transfusions or desmopressin for apixaban-related bleeding—there is no evidence of benefit and platelet transfusion may increase mortality 1
• Do not use vitamin K—it has no effect on direct factor Xa inhibitors like apixaban 1, 3
• Do not rely on PT/INR or aPTT to guide management—these tests do not reliably reflect apixaban levels 1
• Avoid NSAIDs in patients on apixaban, as NSAID use dramatically increases major bleeding risk (HR 10.25) 4
• Be cautious with shortened lead-in therapy—if transitioning from parenteral anticoagulation with reduced apixaban 10 mg twice daily duration, bleeding risk increases 5

Special Considerations

• Gastrointestinal bleeding is the most common site of major bleeding with apixaban (0.89 per 100 patient-years), occurring more frequently than with aspirin 4
• Intracranial and fatal bleeding rates are relatively low and similar to aspirin 4
• Risk factors for major bleeding include NSAID use, active cancer, advanced age, and impaired renal function 4
• Most major bleeding events are nonemergencies characterized by hemoglobin drop ≥2 g/dL rather than critical site bleeding 4