What are the perioperative holding and restarting guidelines for apixaban (Eliquis) in a patient with Factor V Leiden undergoing surgical excision of a thrombosed hemorrhoid?

Perioperative Management of Apixaban for Thrombosed Hemorrhoid Excision in Factor V Leiden Patient

For excision of a thrombosed hemorrhoid, hold apixaban (Eliquis) for 48 hours before the procedure (last dose on the morning of the day before surgery if taken twice daily), and resume at least 6 hours after the procedure once adequate hemostasis is achieved—no bridging anticoagulation is needed despite Factor V Leiden status. 1

Preoperative Holding Protocol

Classification of Bleeding Risk

Hemorrhoid excision is classified as a low-to-moderate bleeding risk procedure where surgical hemostasis can be readily achieved. 1 This is distinct from high-risk procedures like intracranial neurosurgery or neuraxial anesthesia. 1

Specific Holding Instructions for Apixaban

For twice-daily apixaban dosing (most common):

• Last dose: Morning of the day before surgery (D-1) 1
• This provides approximately 48 hours of drug clearance before the procedure 2

For once-daily morning dosing:

• Last dose: Morning of the day before surgery (D-1) 1

For once-daily evening dosing:

• Last dose: Two days before surgery (D-2) 1

Critical Considerations Before Holding

Assess renal function using Cockcroft-Gault formula for creatinine clearance (CrCl), as this significantly impacts apixaban elimination. 3, 4

• If CrCl >30 mL/min: Standard 48-hour holding period applies 1
• If CrCl 30-50 mL/min or age ≥80 years: Consider extending holding period to 72 hours (3 days) 1, 3
• If CrCl <30 mL/min: Extend holding to 72 hours minimum 3

Recent evidence shows that 13.1% of apixaban patients had residual drug levels ≥30 ng/mL despite following standard protocols, particularly with decreased kidney function and shorter interruption times. 4

Bridging Anticoagulation Decision

Do NOT use bridging anticoagulation with heparin or low-molecular-weight heparin. 1, 3

This recommendation applies even though your patient has Factor V Leiden mutation. Here's why:

• Bridging increases bleeding risk without reducing thrombotic complications 1, 3
• Multiple large trials have demonstrated increased hemorrhagic risk with bridging in atrial fibrillation patients on DOACs 1
• Factor V Leiden alone does not justify bridging for a brief 48-hour interruption 5, 6
• The thrombotic risk during a 48-hour interruption for a minor procedure is extremely low, even in Factor V Leiden carriers 5, 6

Factor V Leiden Context

Factor V Leiden increases venous thromboembolism risk 4-5 fold for recurrent events after initial treatment, but this elevated risk does not translate to requiring bridging for brief perioperative interruptions. 6 The mutation does not play a role in hemorrhoidal thrombosis pathophysiology. 7

Postoperative Resumption Protocol

Timing of Restart

Resume apixaban at least 6 hours after procedure completion once adequate hemostasis is established. 1, 8

Specific restart schedule:

• Twice-daily regimen: Resume the evening of surgery day (same day as procedure) 1
• Once-daily morning regimen: Resume the next morning (D+1) 1
• Once-daily evening regimen: Resume the evening of surgery day 1

Hemostasis Assessment

Before restarting, verify:

• No active bleeding from surgical site 1, 8
• Adequate surgical hemostasis achieved 8, 2
• No surgical contraindication to anticoagulation 1

If bleeding persists or hemostasis is inadequate, delay resumption to 24-48 hours and consider mechanical or pharmacologic VTE prophylaxis (not full anticoagulation) in the interim. 1, 8

Alternative Approach for High Thrombotic Risk

Given Factor V Leiden status, if there is concern about thrombotic risk during delayed restart:

• Consider starting prophylactic-dose heparin or fondaparinux at least 6 hours post-procedure 8
• Then transition to full-dose apixaban at 12-24 hours when hemostasis is secure 8
• However, for hemorrhoid excision specifically, this is typically not necessary 1

Common Pitfalls to Avoid

Do NOT:

• Measure apixaban levels or coagulation parameters before the procedure—this is not routinely indicated and does not predict bleeding risk 1, 9
• Use bridging anticoagulation—this significantly increases bleeding without benefit 1, 3, 9
• Resume apixaban too early (within 6 hours)—wait for adequate hemostasis 1, 8
• Extend holding period beyond necessary—this increases thrombotic risk unnecessarily, even in Factor V Leiden patients 1, 6
• Double the dose if a dose is missed—simply resume the regular schedule 2

Critical Safety Points:

• Verify recent creatinine clearance calculation before determining holding duration 3, 4
• Ensure patient understands to stop taking apixaban at the specified time 2
• Confirm no concomitant P-glycoprotein or strong CYP3A4 inhibitors that could prolong apixaban effect 8, 2
• Document clear restart instructions for the patient 8