Perioperative Management of Apixaban
For patients undergoing elective surgery on apixaban, discontinue the drug 1 day (24 hours) before low-to-moderate bleeding risk procedures and 2 days (48 hours) before high bleeding risk procedures, with longer interruption periods required for patients with impaired renal function. 1
Preoperative Discontinuation Strategy
Standard Timing Based on Bleeding Risk
For patients with normal or mildly impaired renal function (CrCl ≥50 mL/min):
- Low-to-moderate bleeding risk procedures: Stop apixaban 1 day before surgery (skip 2 doses), corresponding to 2-3 half-lives and 3-6% residual anticoagulant effect 1, 2
- High bleeding risk procedures: Stop apixaban 2 days before surgery (skip 4 doses), corresponding to 4 half-lives and minimal (6%) residual anticoagulant effect 1, 2
For patients with moderate renal impairment (CrCl 30-50 mL/min):
- Low-to-moderate bleeding risk: Stop apixaban 3 days before surgery (skip 4 doses) 1
- High bleeding risk: Stop apixaban 4 days before surgery (skip 6 doses) 1
The FDA label mandates discontinuation at least 48 hours prior to moderate-to-high bleeding risk procedures and at least 24 hours prior to low bleeding risk procedures 3.
Defining Bleeding Risk Categories
High bleeding risk procedures include: cardiac surgery, intracranial/spinal surgery, major abdominal surgery 2
Low-to-moderate bleeding risk procedures include: arthroscopy, colonoscopy with biopsy, abdominal hernia repair 2
Critical Considerations for Renal Impairment
While apixaban has only 25% renal clearance (the lowest among DOACs), patients with severe CKD or ESKD can still accumulate drug and experience catastrophic bleeding, including rare sites such as pleural, pericardial, and intracranial hemorrhage 1, 4. Extended preoperative interruption is essential in patients with declining renal function, even if baseline function was acceptable 1, 4.
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) 5.
Postoperative Resumption Strategy
Timing Based on Bleeding Risk
For low bleeding risk surgery:
- Resume apixaban 24 hours postoperatively at the usual dose (5 mg twice daily) 1, 2
- Ensure at least 6 hours have elapsed after the invasive procedure and adequate hemostasis is established 2, 3
For high bleeding risk surgery:
- Resume apixaban 2-3 days (48-72 hours) after surgery 1, 2
- Consider reduced dose (2.5 mg twice daily) for the first 2-3 days in patients at high thromboembolism risk, then increase to full dose (5 mg twice daily) 1
The FDA label emphasizes restarting "as soon as adequate hemostasis has been established" 3.
Important Postoperative Considerations
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) 1. This rapid peak effect is similar to LMWH and poses bleeding risk if hemostasis is incomplete 1.
Account for factors affecting drug absorption: postoperative bowel dysmotility and acid-suppressive therapy may impair absorption after major abdominal surgery 2.
Bridging Anticoagulation
Bridging with heparin or LMWH is NOT recommended during the perioperative period 1, 2, 3. 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" 3.
Evidence from the RE-LY trial subanalysis demonstrated that perioperative LMWH bridging increased major bleeding risk (6.5% vs 1.8%, P<0.001) without reducing stroke/systemic embolism 1.
Common Pitfalls and Caveats
Do not rely solely on baseline renal function: Patients with declining renal function require extended interruption periods even if initial CrCl was acceptable 4. A case report documented fatal intracranial hemorrhage in a patient whose renal function deteriorated from stage 3b CKD to ESKD while on apixaban 4.
Avoid premature resumption after high-risk surgery: The rapid onset of apixaban's anticoagulant effect means full therapeutic dosing too soon after surgery can precipitate major bleeding 1.
Monitor for rare bleeding sites: While gastrointestinal bleeding is most common, apixaban can cause hemorrhagic pleural effusions, pericardial effusions, and intracranial hemorrhage, particularly in patients with severe renal impairment 4.
Do not measure routine coagulation tests: Standard INR and aPTT are not useful for monitoring apixaban effect 1. Anti-Xa activity correlates well with apixaban exposure if measurement is needed 5.