How should apixaban (Eliquis) be held before a scheduled procedure in a patient with factor V Leiden, taking into account the procedure’s bleeding risk, renal function, and age?

Perioperative Management of Apixaban in Patients with Factor V Leiden

For patients with Factor V Leiden on apixaban undergoing elective procedures, hold apixaban for 48 hours before low-to-moderate bleeding risk procedures and 72 hours (3 days) before high bleeding risk procedures if renal function is normal (CrCl >50 mL/min), with longer holds required for impaired renal function. 1, 2

Preoperative Discontinuation Strategy

The timing of apixaban interruption depends primarily on the procedure's bleeding risk and the patient's renal function, not on the presence of Factor V Leiden itself, as this thrombophilic condition does not alter apixaban pharmacokinetics 3.

Low-to-Moderate Bleeding Risk Procedures

• Hold apixaban for a minimum of 48 hours (skip 2 doses) before the procedure if CrCl >50 mL/min 1, 4, 2
• This corresponds to approximately 4-5 half-lives, resulting in minimal (≤6%) residual anticoagulant effect 1
• The FDA label specifically states apixaban should be discontinued at least 48 hours prior to elective surgery with moderate or high bleeding risk 2

High Bleeding Risk Procedures

• Hold apixaban for 72 hours (3 days) before the procedure if CrCl >30 mL/min 1
• For very high bleeding risk procedures (intracranial neurosurgery, neuraxial anesthesia/spinal puncture), consider extending to 5 days 1
• The French Working Group on Perioperative Hemostasis strongly recommends against performing spinal or epidural anesthesia with insufficient discontinuation time 1

Renal Function Adjustments

Always calculate creatinine clearance using the Cockcroft-Gault formula before determining hold duration 1, 4:

• CrCl >50 mL/min: Standard hold times (48-72 hours depending on bleeding risk) 1, 4
• CrCl 30-50 mL/min: Extend hold to 72 hours minimum for moderate-risk procedures; up to 4-5 days for high-risk procedures 1
• CrCl <30 mL/min: Requires individualized assessment with possible laboratory monitoring 1

Apixaban has 25% renal excretion, making renal impairment less critical than with dabigatran, but still requires adjustment 1, 5.

Drug Interaction Assessment

Check for P-glycoprotein (P-gp) and CYP3A4 inhibitors that may prolong apixaban clearance 1, 4:

• Strong combined P-gp and CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir) increase apixaban levels 2
• If taking these inhibitors, extend the hold period by an additional 24 hours 4
• Consider this particularly important in patients with Factor V Leiden given their baseline thrombotic risk 3

Bridging Anticoagulation

Do not use heparin bridging (UFH or LMWH) for elective procedures in Factor V Leiden patients on apixaban 1, 4, 2:

• The FDA label states bridging anticoagulation during the 24-48 hours after stopping apixaban is not generally required 2
• Bridging increases major bleeding risk without reducing stroke or systemic embolism 4
• The only exception is patients at very high thrombotic risk, which would require multidisciplinary discussion 1

Factor V Leiden heterozygotes have only a modestly increased thrombotic risk and do not routinely require long-term anticoagulation in the absence of prior thrombosis 3. The short interruption period for apixaban (48-72 hours) poses minimal thrombotic risk even in these patients.

Laboratory Monitoring

Routine preoperative measurement of apixaban levels is not necessary when recommended interruption periods are followed 1, 4:

• Standard coagulation tests (INR, aPTT) are not useful for monitoring apixaban 4
• If needed for very high-risk procedures, chromogenic anti-Xa assays can measure apixaban levels 5
• A recent study found 7.6% of patients had levels ≥30 ng/mL at surgery following standard protocols, with 13.1% for apixaban specifically 6
• However, these elevated levels were not associated with increased surgical blood loss 6

Postoperative Resumption

Resume apixaban at least 6 hours after the procedure once adequate hemostasis is confirmed 1, 4:

Low Bleeding Risk Procedures

• Resume full-dose apixaban (5 mg twice daily) 6 hours after the procedure 1
• Can resume the evening of surgery if the procedure was in the morning 1

High Bleeding Risk Procedures

• Resume at 24 hours (next day) after low-risk surgery 1
• Resume at 48-72 hours (2-3 days) after high bleeding risk surgery 1, 4
• Consider reduced dose (2.5 mg twice daily) for first 2-3 days in patients at high thrombotic risk, then increase to full dose 1

If venous thromboprophylaxis is needed before resuming apixaban, use UFH or LMWH at least 6 hours after the procedure 1.

Common Pitfalls to Avoid

• Do not assume 24 hours is sufficient: The FDA label and guidelines clearly require 48 hours minimum for moderate-to-high bleeding risk procedures 4, 2
• Do not forget to assess renal function: Impaired clearance (CrCl 30-50 mL/min) necessitates 72-hour holds minimum 1, 4
• Do not bridge with heparin routinely: This increases bleeding without benefit in most patients 1, 4
• Do not resume apixaban too early: Confirm hemostasis before restarting; for major surgery wait 24-72 hours 1, 4
• Do not ignore drug interactions: P-gp and CYP3A4 inhibitors require extended hold periods 1, 4
• Do not treat Factor V Leiden differently: The thrombophilic condition does not change apixaban pharmacokinetics or standard perioperative protocols 3
• Do not perform neuraxial anesthesia without adequate drug clearance: This carries high risk of spinal hematoma 1, 2