When can Eliquis (apixaban) be restarted after major surgery in a patient with impaired renal function?

Restarting Eliquis After Major Surgery in Patients with Impaired Renal Function

For patients with impaired renal function undergoing major surgery, restart apixaban 48-72 hours postoperatively once adequate hemostasis is established, and consider using a reduced dose (2.5 mg twice daily) for the first 2-3 days before advancing to full therapeutic dosing. 1

Timing of Resumption Based on Bleeding Risk

High Bleeding Risk Surgery (Major Surgery)

• Resume apixaban 48-72 hours (2-3 days) after surgery once adequate hemostasis has been confirmed 1, 2
• The FDA label states apixaban should be restarted "as soon as adequate hemostasis has been established" after surgical procedures 3
• Examples of high bleeding risk procedures include cardiac surgery, intracranial/spinal surgery, major abdominal surgery, hepatic surgery, and surgery in highly vascular organs 2, 4

Low Bleeding Risk Surgery

• Resume apixaban 24 hours postoperatively with full dose (5 mg twice daily) 1, 2
• This shorter interval is appropriate only when bleeding risk is minimal and hemostasis is secure 2

Dosing Strategy for Major Surgery

Initial Reduced Dosing Approach

• For high thrombotic risk patients undergoing major surgery, initiate with reduced dose apixaban 2.5 mg twice daily for the first 2-3 days 1, 2
• After 2-3 days on reduced dosing, advance to full therapeutic dose (5 mg twice daily, or 2.5 mg twice daily if dose reduction criteria are met) 1, 2
• This stepwise approach balances thrombotic risk against early postoperative bleeding risk 1

Alternative Approach with Bridging

• Consider prophylactic-dose LMWH starting 6-8 hours after surgery if there are concerns about bleeding, then delay apixaban for 48 hours 1
• Continue LMWH in the interim period for high thrombotic risk patients 1
• However, the American College of Chest Physicians generally recommends against routine bridging anticoagulation during apixaban interruption, as it increases hemorrhagic risk without reducing thrombotic events 2

Special Considerations for Impaired Renal Function

Impact of Renal Impairment

• Apixaban has 25-27% renal clearance, making renal function assessment mandatory before determining resumption timing 2, 5
• For patients with moderate renal impairment (CrCl 30-50 mL/min), consider longer interruption periods and delayed resumption 1
• The 2025 Association of Anaesthetists guideline specifically recommends 3 days of preoperative cessation for patients with CrCl <30 mL/min, suggesting these patients may also require more cautious postoperative resumption 1

Dose Adjustment Criteria

• Use apixaban 2.5 mg twice daily (rather than 5 mg twice daily) if the patient meets at least two of the following criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 3
• These dose reduction criteria are particularly relevant in patients with impaired renal function 3

Critical Safety Checks Before Resumption

Mandatory Assessments

• Verify adequate hemostasis at the surgical site - no active bleeding or oozing 1, 2
• Check postoperative renal function (creatinine clearance) as surgery and perioperative factors can worsen baseline renal impairment 2
• Confirm hemoglobin/hematocrit stability if there is any suspicion of occult bleeding 2
• Ensure no epidural catheter is in place - do not resume therapeutic-dose apixaban with an indwelling epidural catheter 2

Contraindications to Resumption

• Active or uncontrolled bleeding 2
• Hemostasis not completely established 2
• Planned additional surgery or invasive procedure 2

Balancing Thrombotic vs Bleeding Risk

High Thrombotic Risk Scenarios

• Recent VTE (within 3 months): risk of recurrence without anticoagulation is very high, and surgery increases risk further 1
• Atrial fibrillation with recent stroke/TIA (within 3 months) or CHA₂DS₂-VASc score with multiple risk factors 1
• For these patients, the reduced-dose stepwise approach (2.5 mg twice daily initially) is particularly important to balance risks 1, 2

The Evidence Base

The most recent 2025 guidelines from the Association of Anaesthetists provide an algorithm showing resumption at 48-72 hours for high bleeding risk surgery, with consideration of prophylactic LMWH bridging if bleeding concerns persist 1. This aligns with the 2012 Blood guidelines that established the framework for DOAC perioperative management 1. The FDA label defers specific timing to clinical judgment regarding hemostasis 3.

Common Pitfalls to Avoid

• Do not use INR or aPTT to guide resumption timing - apixaban's effect on these tests is inconsistent and unreliable 2
• Do not routinely measure apixaban concentrations when following recommended resumption intervals 2
• Do not resume full therapeutic dose immediately after major surgery - use stepwise approach for high-risk patients 1, 2
• Do not forget to reassess renal function postoperatively - perioperative changes can significantly affect apixaban clearance 2