For a patient on apixaban scheduled for surgery, how long should the medication be held based on bleeding risk and is heparin bridging recommended, particularly in those with high thrombotic risk?

Perioperative Management of Apixaban

For patients on apixaban undergoing elective surgery, hold the medication for 1 day (24 hours) before low-to-moderate bleeding risk procedures and 2 days (48 hours) before high bleeding risk procedures, and do not use heparin bridging regardless of thrombotic risk. 1

Preoperative Apixaban Interruption

Low-to-Moderate Bleeding Risk Procedures

• Stop apixaban 1 day (24 hours) before surgery, which corresponds to approximately 2-3 half-lives and allows minimal residual anticoagulant effect at the time of the procedure 1
• Examples include arthroscopy, colonoscopy with biopsy, and abdominal hernia repair 1
• The FDA label recommends discontinuation at least 24 hours prior to elective surgery or invasive procedures with low bleeding risk 2

High Bleeding Risk Procedures

• Stop apixaban 2 days (48 hours) before surgery, corresponding to approximately 4 half-lives and resulting in only 6% residual anticoagulant effect 1, 3
• Examples include cardiac surgery, intracranial/spinal surgery, and major abdominal surgery 3
• The FDA label recommends discontinuation at least 48 hours prior to procedures with moderate or high risk of unacceptable or clinically significant bleeding 2
• Real-world data from 111 patients showed that 94% achieved apixaban concentrations ≤30 ng/mL with a median cessation time of 76 hours, confirming the safety of this approach 4

Renal Function Considerations

• For patients with creatinine clearance 30-50 mL/min, consider extending the interruption period by 1 additional day for high bleeding risk procedures 1
• Apixaban has 25% renal clearance, making it less dependent on kidney function than dabigatran but still requiring adjustment in moderate renal impairment 1, 3
• The PAUSE study excluded patients with severe renal insufficiency (CrCl <25 mL/min for apixaban) 1

Heparin Bridging: Not Recommended

Bridging anticoagulation with heparin is not recommended for patients on apixaban, even in those with high thrombotic risk. 1, 3

Evidence Against Bridging

• The PAUSE study demonstrated excellent outcomes without bridging: only 0.16% arterial thromboembolism rate and 1.35% major bleeding rate in 1,257 apixaban-treated patients 1
• Retrospective analyses of major DOAC trials showed that 15-20% of patients who received heparin bridging had comparable or worse outcomes (2-5% major bleeding) compared to standardized DOAC interruption without bridging 1
• The FDA label explicitly states that "bridging anticoagulation during the 24 to 48 hours after stopping apixaban and prior to the intervention is not generally required" 2
• Updated French guidelines specifically moved away from routine bridging based on evidence showing increased hemorrhagic risk without thrombotic risk reduction 1, 3

Exception for Extremely High Risk

• Reserve bridging only for very rare, extremely high thrombotic risk patients through multidisciplinary discussion (e.g., mechanical mitral valve, recent stroke within 1 month) 3
• Even in atrial fibrillation patients with prior stroke, the short interruption period (2-4 days total) makes bridging unnecessary 1

Postoperative Apixaban Resumption

Low-to-Moderate Bleeding Risk Procedures

• Resume apixaban 24 hours after surgery at the usual dose (5 mg twice daily), ensuring adequate hemostasis has been established 1, 3
• Can resume as early as 6 hours postoperatively for very low bleeding risk procedures 1, 3
• The FDA label confirms restarting "as soon as adequate hemostasis has been established" 2

High Bleeding Risk Procedures

• Resume apixaban 48-72 hours (2-3 days) after surgery to allow sufficient time for surgical site hemostasis 1, 3
• Consider using a reduced dose (2.5 mg twice daily) for the first 2-3 days in patients at high thrombotic risk, then increase to full dose (5 mg twice daily) 1, 3
• For patients requiring earlier thromboprophylaxis, use low-dose LMWH for the initial 2-3 days before transitioning to therapeutic apixaban 1

Critical Pitfalls to Avoid

Do Not Routinely Measure Apixaban Levels

• Routine coagulation tests (INR, aPTT) are insensitive for detecting residual apixaban effect and should not guide management 1
• DOAC-calibrated anti-factor Xa levels are more sensitive but their clinical utility remains questionable when standardized interruption protocols are followed 1, 3
• The DALI study showed that following the standardized protocol resulted in appropriate drug clearance in 92.4% of patients without needing level monitoring 5

Do Not Resume Therapeutic Anticoagulation Too Early

• Premature resumption increases major bleeding risk without reducing thrombotic events 1, 3
• Studies of early LMWH resumption (<24 hours) after major surgery showed up to 20% major bleeding rates 1
• Wait for adequate surgical hemostasis, which typically requires at least 24 hours for low-risk and 48-72 hours for high-risk procedures 1

Special Considerations for Neuraxial Anesthesia

• Do not resume therapeutic-dose apixaban while an epidural catheter is in place due to spinal hematoma risk 3, 2
• The FDA label warns about the risk of epidural or spinal hematomas with neuraxial anesthesia in anticoagulated patients 2

Account for Postoperative Factors

• Consider delayed absorption after major abdominal surgery due to bowel dysmotility 3
• Monitor renal function postoperatively if the procedure could affect kidney function and adjust timing accordingly 3

Algorithm Summary

Preoperative:

1. Assess surgical bleeding risk (low-moderate vs. high)
2. Check renal function (CrCl)
3. Stop apixaban 1 day before low-risk OR 2 days before high-risk procedures
4. Extend by 1 day if CrCl 30-50 mL/min for high-risk procedures
5. Do NOT bridge with heparin

Postoperative:

1. Ensure adequate hemostasis
2. Resume at 24 hours for low-risk procedures (full dose)
3. Resume at 48-72 hours for high-risk procedures
4. Consider reduced dose (2.5 mg BID) for first 2-3 days in high thrombotic risk patients undergoing high-risk surgery
5. Use prophylactic LMWH if delaying >72 hours in high VTE risk patients