What is the protocol for managing Eliquis (apixaban) in patients undergoing surgery?

Eliquis (Apixaban) Perioperative Management Protocol

For most elective surgeries, discontinue Eliquis at least 48 hours before procedures with moderate-to-high bleeding risk and at least 24 hours before low bleeding risk procedures, with timing adjusted based on renal function; do not use heparin bridging; and resume at least 6 hours postoperatively once hemostasis is established. 1

Preoperative Discontinuation Timeline

Standard Patients (CrCl >50 mL/min)

Low Bleeding Risk Procedures:

• Discontinue 24 hours (1 day) before surgery 2, 1
• Examples include arthroscopy, colonoscopy with biopsy, abdominal hernia repair 3
• This corresponds to 2-3 half-lives with 3-6% residual anticoagulant effect 2

Moderate-to-High Bleeding Risk Procedures:

• Discontinue 48 hours (2 days) before surgery 4, 2, 1
• Examples include cardiac surgery, intracranial/spinal surgery, major abdominal surgery, port placement 3
• This corresponds to approximately 4 half-lives with minimal (6%) residual anticoagulant effect 3

Very High Bleeding Risk Procedures:

• Discontinue 72 hours (3 days) before surgery for neuraxial anesthesia/puncture or intracranial neurosurgery 5, 3

Patients with Impaired Renal Function (CrCl 30-50 mL/min)

Always assess creatinine clearance using the Cockcroft-Gault formula before determining hold duration 4:

• Low-to-moderate bleeding risk: Extend hold to 72 hours (3 days) 4, 2
• High bleeding risk: Extend hold to 96 hours (4 days) 3, 2
• Apixaban has 25% renal clearance, making renal function assessment critical 3

Drug Interaction Considerations

Check for P-glycoprotein and CYP3A4 inhibitors 4:

• If patient is taking strong P-gp or CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir), consider extending the hold period by an additional 24 hours 4
• These interactions can prolong apixaban clearance and increase bleeding risk 4

Bridging Anticoagulation

Do not use heparin bridging 5, 4, 2, 1:

• Preoperative bridging with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) is not recommended 5
• Bridging increases major bleeding risk without reducing stroke or systemic embolism 2
• The RE-LY trial subanalysis demonstrated that perioperative LMWH bridging increased major bleeding without benefit 2

Postoperative Resumption

Low Bleeding Risk Surgery

• Resume 6-24 hours after surgery at usual dose (5 mg twice daily) 3, 1
• Ensure adequate hemostasis is established before restarting 4, 1
• The Anaesthesia journal recommends waiting at least 6 hours after the end of the invasive procedure 3

High Bleeding Risk Surgery

• Resume 48-72 hours (2-3 days) after surgery 3, 2
• Consider reduced dose (2.5 mg twice daily) for the first 2-3 days in patients at high thromboembolism risk 3
• Avoid rapid resumption at full therapeutic doses immediately after major surgery due to apixaban's rapid onset of action 2

Dosing Schedule Based on Regimen

For twice-daily dosing (standard 5 mg BID regimen) 5:

• Resume the evening of surgery day if low bleeding risk
• Resume the next morning if once-daily morning regimen
• Delay 2-3 days if high bleeding risk

Special Considerations

Neuraxial Anesthesia

The FDA label strongly warns against performing spinal or epidural anesthesia in patients with possible apixaban concentration 1:

• Optimal timing between apixaban administration and neuraxial procedures is not known 1
• Risk of epidural or spinal hematoma is increased with indwelling epidural catheters, concomitant NSAIDs, or history of spinal procedures 1
• Monitor patients frequently for signs of neurological impairment 1

Postoperative Absorption Factors

• Account for factors affecting drug absorption, such as bowel dysmotility after major abdominal surgery 3
• Acid-suppressive therapy may affect absorption 2

Laboratory Monitoring

• Standard coagulation tests (INR, aPTT) are not useful for monitoring apixaban effect 2
• Anti-Xa activity correlates well with apixaban exposure if measurement is needed 2
• There is no reason to routinely measure apixaban concentration before procedures 5

Common Pitfalls to Avoid

Do not assume 24 hours is sufficient for all procedures 4:

• Port placement and moderate-to-high bleeding risk procedures require at least 48 hours 4

Do not forget to assess renal function 4:

• Impaired clearance necessitates longer hold times 4
• Patients with declining renal function can accumulate apixaban and experience catastrophic bleeding 2

Do not bridge with heparin routinely 4:

• This increases bleeding without benefit 4, 2

Do not resume apixaban too early 4:

• Confirm hemostasis before restarting anticoagulation 4
• Premature resumption can precipitate major bleeding due to rapid onset of action 2

Do not ignore drug interactions 4:

• P-gp and CYP3A4 inhibitors require extended hold periods 4

Evidence from Real-World Practice

A prospective cohort study (ADIOS) demonstrated that apixaban discontinuation for at least 48 hours before surgery resulted in clinically insignificant anticoagulation (94% of patients achieved concentrations ≤30 ng/mL), with minimal bleeding complications 6. The median time between last dose and presurgery sampling was 76 hours for those achieving safe concentrations 6.