How long should a patient with normal kidney function and possible history of bleeding or thromboembolism be off apixaban (generic name: apixaban) before undergoing surgery?

Apixaban Preoperative Discontinuation

For patients with normal kidney function, stop apixaban 2 days (48 hours) before low-to-moderate bleeding risk surgery and 3 days (72 hours) before high bleeding risk surgery. 1, 2

Discontinuation Timeline by Bleeding Risk

Low-to-Moderate Bleeding Risk Procedures

• Last dose should be 2 days before surgery (skip 2 doses of the twice-daily regimen), which corresponds to 2-3 half-lives and achieves 3-6% residual anticoagulant effect 3, 1, 2
• Examples include arthroscopy, laparoscopic cholecystectomy, abdominal hernia repair, colonoscopy with biopsy, and coronary angiography 1, 2
• The FDA label recommends discontinuing at least 24 hours prior for low bleeding risk procedures 4

High Bleeding Risk Procedures

• Last dose should be 3 days before surgery (skip 4 doses), which corresponds to 4-5 half-lives and achieves minimal residual anticoagulant effect 3, 1, 2
• High-risk procedures include cardiac surgery, intracranial or spinal surgery, surgery in highly vascular organs, and any major operation 1, 2
• The FDA label recommends discontinuing at least 48 hours prior for moderate-to-high bleeding risk procedures 4

Special Consideration: Neuraxial Procedures

• A full 72-hour (3-day) discontinuation period is mandatory for spinal or epidural anesthesia, even in patients with normal renal function, due to the catastrophic risk of epidural hematoma 1, 2

Pharmacokinetic Rationale

• Apixaban has a half-life of 7-8 hours in patients with normal renal function 3, 1, 5
• Only 27% of total clearance is renal, with the remainder via metabolism, biliary excretion, and direct intestinal excretion 1, 5
• Peak concentration occurs 3-4 hours after oral administration 5
• Real-world data confirms that discontinuation for at least 48 hours results in clinically insignificant anticoagulation (94% of patients achieved apixaban concentrations ≤30 ng/mL) 6

Adjustments for Renal Impairment

Moderate Renal Impairment (CrCl 30-50 mL/min)

• Low-to-moderate bleeding risk: Last dose 3 days before surgery (skip 4 doses) 3, 2
• High bleeding risk: Last dose 4 days before surgery (skip 6 doses) 3, 2

Severe Renal Impairment

• Extended preoperative interruption is essential, as patients with severe chronic kidney disease can accumulate apixaban and experience catastrophic bleeding 2
• Renal function assessment is mandatory before determining the discontinuation timeline 1

Critical Management Points

Bridging Anticoagulation

• Bridging with heparin or LMWH is NOT recommended during the 24-72 hour interruption period due to apixaban's rapid offset and onset of action 1, 2, 4
• Bridging increases major bleeding risk without reducing stroke or systemic embolism 2

Monitoring Limitations

• Do not use INR or aPTT to guide surgical timing, as apixaban's effect on these tests is inconsistent and unreliable 1, 2
• Anti-Xa activity correlates well with apixaban exposure if measurement is needed 2

Postoperative Resumption

• Resume apixaban at least 24 hours after low bleeding risk surgery, once adequate hemostasis is established 1, 2, 4
• For high bleeding risk procedures, consider resuming at 2-3 days postoperatively 1, 2
• Avoid rapid resumption at full therapeutic doses immediately after major surgery due to apixaban's rapid onset of action (peak levels at 1-3 hours) 2

Common Pitfalls to Avoid

• Do not assume standard coagulation tests reflect apixaban levels - they are unreliable for surgical clearance 1, 2
• Do not use shorter discontinuation periods for neuraxial procedures - the 72-hour rule is non-negotiable regardless of other risk factors 1, 2
• Do not forget to account for declining renal function - even if baseline function was acceptable, deterioration requires extended interruption 2
• Do not resume too early after high-risk surgery - premature resumption can precipitate major bleeding due to rapid onset of action 2