Bleeding Risk with Apixaban Stopped 48 Hours Before Surgery
For a typical adult with normal renal function (CrCl >80 mL/min) taking apixaban 5 mg twice daily, stopping the drug 48 hours (2 days) before high bleeding risk surgery results in minimal residual anticoagulant effect and is the standard recommended approach, with major bleeding rates of approximately 1.35% and arterial thromboembolism rates of 0.16% based on prospective trial data. 1
Evidence-Based Discontinuation Strategy
Standard Recommendations for Normal Renal Function
High bleeding risk procedures require apixaban discontinuation 48 hours before surgery, corresponding to approximately 4 half-lives and achieving minimal residual anticoagulant effect. 2, 1
The FDA label explicitly states that apixaban should be discontinued at least 48 hours prior to elective surgery or invasive procedures with moderate or high risk of unacceptable or clinically significant bleeding. 3
For low-to-moderate bleeding risk procedures, only 24 hours (1 day) of discontinuation is required, corresponding to 2-3 half-lives and 3-6% residual anticoagulant effect. 2, 1
Supporting Safety Data
The PAUSE trial (1,257 apixaban patients) demonstrated that following these interruption intervals resulted in major bleeding in 1.35% and arterial thromboembolism in 0.16% of patients, confirming the safety of the 48-hour protocol for high-risk procedures. 1
A prospective observational study (ADIOS) found that 94% of patients achieved apixaban concentrations ≤30 ng/mL after discontinuation, with only one clinically significant non-major bleeding event reported at 1 week post-surgery. 4
Pharmacokinetic Rationale
Apixaban has a half-life of 7-8 hours in patients with normal renal function, with 27% of total clearance being renal. 5, 1
Stopping 48 hours before surgery allows for 4 half-lives to elapse, achieving minimal anticoagulant effect suitable for high bleeding risk procedures. 5, 1
The time to minimal anticoagulation is 2-3 half-lives (mild residual effect) and 4-5 half-lives (minimal effect). 5
Critical Considerations and Caveats
Special Procedure Requirements
Neuraxial procedures (spinal/epidural anesthesia) require a 72-hour (3-day) discontinuation period regardless of renal function, due to the catastrophic risk of epidural hematoma and potential paralysis. 5, 1, 3
The FDA label specifically warns about epidural or spinal hematomas in patients receiving neuraxial anesthesia, which may result in long-term or permanent paralysis. 3
Bridging Anticoagulation
- Bridging with heparin or low molecular weight heparin is NOT recommended during the 24-48 hour interruption period, as apixaban's rapid offset and onset of action eliminate the need, and bridging increases bleeding risk without reducing thromboembolism. 1, 6, 3
Laboratory Monitoring Pitfall
Standard coagulation tests (INR, aPTT) are unreliable for assessing apixaban effect and should not guide surgical timing decisions. 1, 6
If quantitative measurement is required, use a DOAC-calibrated anti-factor Xa assay, though clinical utility remains uncertain. 1, 6
Postoperative Resumption
For high bleeding risk surgery, restart apixaban 48-72 hours postoperatively after adequate hemostasis is established, acknowledging apixaban's rapid peak effect (1-3 hours). 1, 3
Avoid premature resumption at full therapeutic doses immediately after major surgery, as this can precipitate major bleeding if hemostasis is incomplete. 1, 6
For low-to-moderate bleeding risk surgery, apixaban can be resumed ≥24 hours after surgery once adequate hemostasis is confirmed. 1, 3
Drug Interactions Requiring Extended Interruption
- When patients are on P-glycoprotein inhibitors (e.g., dronedarone, amiodarone, verapamil), add an extra 24 hours of interruption, especially if thromboembolic risk is modest. 1