What are the guidelines for managing apixaban (direct oral anticoagulant) in patients undergoing surgery?

Perioperative Management of Apixaban

Preoperative Discontinuation

For high bleeding risk surgeries (cardiac, intracranial/spinal, major abdominal), discontinue apixaban 2-3 days (48-72 hours) before the procedure, which allows approximately 4 half-lives to elapse and results in minimal (6%) residual anticoagulant effect. 1, 2

High Bleeding Risk Procedures

• Stop apixaban 3 days (72 hours) preoperatively for surgeries such as cardiac surgery, intracranial/spinal surgery, and major abdominal surgery in patients with normal renal function 3, 1
• The FDA label recommends discontinuation at least 48 hours prior to elective surgery with moderate or high risk of unacceptable bleeding 2
• For neuraxial anesthesia (epidural/spinal), longer interruption times are suggested due to the risk of epidural or spinal hematoma 3, 2
• Consider extending the interruption period to 4 days in patients with moderate renal impairment (CrCl 30-50 mL/min), as apixaban has 25% renal clearance 1

Low-to-Moderate Bleeding Risk Procedures

• Discontinue apixaban 1-2 days (24-48 hours) before surgery for procedures such as arthroscopy, colonoscopy with biopsy, and abdominal hernia repair 1, 2
• The French Working Group recommends stopping apixaban the night before (last intake on the morning of the day before) for low bleeding risk procedures 3
• For minimal bleeding risk procedures like dental fillings and cataract surgery with topical anesthesia, apixaban can be continued without interruption 4, 5

Renal Function Considerations

• Apixaban is less dependent on renal clearance (25%) compared to other DOACs, but longer interruption should still be considered in patients with impaired renal function 1
• Monitor creatinine clearance preoperatively and adjust timing accordingly 3

Bridging Anticoagulation

Preoperative bridging with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) is not recommended for routine perioperative management of apixaban. 3, 1, 2

• Bridging is not generally required during the 24-48 hours after stopping apixaban and prior to intervention 2
• The updated guidelines from 2015-2017 specifically moved away from routine bridging based on evidence showing increased hemorrhagic risk without thrombotic risk reduction 3
• Reserve bridging only for very high thrombotic risk patients, which should be determined by multidisciplinary discussion 3

Postoperative Resumption

Resume apixaban 2-3 days (48-72 hours) after high bleeding risk surgery once adequate hemostasis is established, with consideration of reduced dose (2.5 mg twice daily) for the first 2-3 days in high thromboembolism risk patients. 1, 2

High Bleeding Risk Surgery

• Wait at least 48-72 hours postoperatively before resuming therapeutic dose apixaban 1
• Consider starting with reduced dose (2.5 mg twice daily) for 2-3 days in patients at high risk for thromboembolism, then transition to full dose 1
• Ensure adequate surgical hemostasis has been achieved before resumption 2

Low Bleeding Risk Surgery

• Resume apixaban on the day after surgery (24 hours postoperatively) at the usual dose (5 mg twice daily) 1
• The minimum waiting period is at least 6 hours after the end of the invasive procedure 3, 1
• For very low bleeding risk procedures, resumption can occur as early as 6 hours postoperatively 3

Bridging with Prophylactic Anticoagulation

• If venous thromboprophylaxis is indicated postoperatively, administer prophylactic-dose LMWH or fondaparinux at least 6 hours after the procedure 3
• When transitioning back to therapeutic apixaban, administer the first therapeutic dose 12 hours after the last prophylactic LMWH dose 3
• Avoid overlapping therapeutic doses when changing between anticoagulant molecules 3

Special Considerations

Epidural Catheter Management

• In the presence of an epidural catheter, do not resume therapeutic-dose apixaban 3
• Use heparin for therapeutic anticoagulation to allow safe catheter removal according to neuraxial anesthesia guidelines 3
• The FDA label emphasizes monitoring for neurological impairment and notes that optimal timing between apixaban administration and neuraxial procedures is not known 2

Postoperative Factors Affecting Absorption

• Consider bowel dysmotility after major abdominal surgery, which may affect oral drug absorption 1
• Monitor renal function postoperatively if the procedure could affect kidney function, and adjust dosing accordingly 3

Procedure-Specific Exceptions

• Cataract surgery with topical/sub-Tenon's anesthesia: Continue apixaban without interruption 4
• Dental fillings and minor dental procedures: Continue apixaban, scheduling procedures 12-24 hours after last dose (at trough levels) 5
• Retrobulbar anesthesia for eye surgery: Hold apixaban for 1 day before the procedure due to risk of retrobulbar hematoma 4

Common Pitfalls to Avoid

• Do not routinely measure apixaban concentrations before procedures when recommended interruption periods are followed 3
• Do not use bridging anticoagulation routinely, as it increases bleeding risk without reducing thrombotic events 3, 1
• Do not resume therapeutic anticoagulation too early after high bleeding risk surgery—wait for adequate hemostasis 2
• Do not hold apixaban for minimal bleeding risk procedures like standard cataract surgery or dental fillings, as this exposes patients to unnecessary thromboembolic risk 4, 5
• Do not ignore renal function—apixaban has 25% renal clearance and requires longer interruption in renal impairment 1