How long should Eliquis (apixaban) be held before surgery?

Perioperative Management of Eliquis (Apixaban) for Surgery

For most patients with normal renal function undergoing elective surgery, hold Eliquis for at least 48 hours (2 days) before procedures with moderate-to-high bleeding risk, and at least 24 hours before low bleeding risk procedures. 1

Standard Discontinuation Protocol

Based on Bleeding Risk and Renal Function

For patients with normal or mildly impaired renal function (CrCl ≥50 mL/min):

• Low bleeding risk procedures: Hold for 24 hours (skip 1-2 doses) 2, 3, 1
• Moderate-to-high bleeding risk procedures: Hold for 48 hours (skip 2-4 doses) 2, 3, 1

For patients with moderate renal impairment (CrCl 30-50 mL/min):

• Low bleeding risk procedures: Hold for 72 hours (3 days, skip 4 doses) 2, 3
• High bleeding risk procedures: Hold for 96 hours (4 days, skip 6 doses) 2, 3

Very High Bleeding Risk Procedures

For neuraxial anesthesia, spinal/epidural puncture, or intracranial neurosurgery:

• Hold for 72-120 hours (3-5 days) regardless of renal function 2, 4
• These procedures require complete absence of anticoagulant effect due to catastrophic bleeding potential 2

Critical Assessment Before Holding

Renal Function Evaluation

• Always calculate creatinine clearance using Cockcroft-Gault formula before determining hold duration 2, 4
• Apixaban has a half-life of 7-8 hours in normal renal function, but this extends significantly with renal impairment 2
• Patients with declining renal function require extended preoperative interruption even if baseline function was acceptable 3

Drug Interaction Assessment

• Check for P-glycoprotein (P-gp) and CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir) 2, 4
• If patient is taking strong P-gp or CYP3A4 inhibitors, extend the hold period by an additional 24 hours 4
• These interactions can significantly prolong apixaban clearance 2

Bridging Anticoagulation

Do not use heparin bridging (UFH or LMWH) for routine perioperative management. 2, 4, 3

• Bridging increases major bleeding risk without reducing stroke or systemic embolism 4, 3
• Exception: Consider bridging only for very high thrombotic risk patients (e.g., recent VTE within 3 months) 2

Postoperative Resumption

Timing Based on Hemostasis and Bleeding Risk

For low bleeding risk surgery:

• Resume at 24 hours postoperatively at usual dose once adequate hemostasis is confirmed 3
• Ensure at least 6 hours have elapsed after the procedure 2, 3

For high bleeding risk surgery:

• Resume at 48-72 hours (2-3 days) postoperatively 3
• Consider reduced dose for first 2-3 days in high thromboembolism risk patients 3

Critical consideration: Avoid rapid resumption at full therapeutic doses immediately after major surgery due to apixaban's rapid onset of action, which poses bleeding risk if hemostasis is incomplete 3

Common Pitfalls and How to Avoid Them

Insufficient Hold Duration

• Do not assume 24 hours is sufficient for moderate-to-high bleeding risk procedures 4
• The FDA label explicitly states 48 hours minimum for moderate-to-high bleeding risk 1
• Real-world data confirms that 48-hour discontinuation results in clinically insignificant anticoagulation (94% of patients achieved apixaban concentrations ≤30 ng/mL) 5

Failure to Assess Renal Function

• Do not forget to calculate CrCl before determining hold time 4, 3
• Impaired renal clearance necessitates longer hold times 2
• Patients with severe CKD can accumulate apixaban and experience catastrophic bleeding 3

Inappropriate Bridging

• Do not bridge with heparin routinely—this increases bleeding without benefit 4, 3
• Evidence from clinical trials demonstrates perioperative LMWH bridging increased major bleeding without reducing stroke 3

Premature Resumption

• Do not restart apixaban before confirming adequate hemostasis 4, 3
• Premature resumption after high-risk surgery can precipitate major bleeding due to rapid onset of action 3

Ignoring Drug Interactions

• Do not overlook P-gp and CYP3A4 inhibitors—these require extended hold periods 2, 4

Laboratory Monitoring

• Standard coagulation tests (INR, aPTT) are not useful for monitoring apixaban effect 4, 3
• Anti-Xa activity correlates well with apixaban exposure if measurement is needed 3, 5
• There is no reason to routinely measure apixaban concentration before procedures when recommended interruption periods are followed 2, 4

Special Considerations

Postoperative Absorption Issues

• Account for factors affecting drug absorption after major abdominal surgery, including bowel dysmotility and acid-suppressive therapy 3

Emergency Surgery

• If surgery is urgent and apixaban has not been held adequately, consider prothrombin complex concentrate (PCC) 50 IU/kg 2
• Specific reversal agents are in development but not yet widely available 2