When should Eliquis (apixaban) be held prior to orthopedic surgery?

When to Hold Eliquis Prior to Orthopedic Surgery

For orthopedic surgery, discontinue apixaban at least 48 hours prior to procedures with moderate-to-high bleeding risk, or 24 hours for low bleeding risk procedures. 1

Timing Based on Bleeding Risk and Renal Function

Standard Discontinuation Protocol

• For moderate-to-high bleeding risk orthopedic procedures (including total hip and knee replacements): Hold apixaban at least 48 hours before surgery 1
• For low bleeding risk procedures: Hold apixaban at least 24 hours before surgery 1
• The French Working Group on Perioperative Hemostasis recommends discontinuation up to five days for apixaban ("xabans") when accounting for patient-specific factors 2

Renal Function Considerations

Creatinine clearance significantly impacts apixaban elimination and must guide discontinuation timing: 2

• Calculate creatinine clearance using the Cockcroft-Gault formula before determining hold duration 2
• Patients with CrCl 30-50 mL/min require longer discontinuation periods beyond the standard 48 hours 3
• Approximately 27% of apixaban clearance occurs renally, making renal impairment a critical factor 4

Additional Risk Factors Requiring Extended Hold Times

Consider extending the discontinuation period beyond 48 hours if the patient has: 2

• Age ≥80 years
• Concomitant P-glycoprotein inhibitors (affects all DOACs including apixaban)
• Concomitant CYP3A4 inhibitors (specifically affects apixaban metabolism)
• Body weight ≤60 kg

Neuraxial Anesthesia Considerations

Do NOT perform spinal or epidural anesthesia if there is any possibility of residual apixaban concentration from insufficient discontinuation time. 2

• This is particularly critical in elderly patients (>80 years) or those with renal impairment 2
• Ensure adequate time has elapsed based on the patient's renal function and risk factors before proceeding with neuraxial techniques 2

Bridging Anticoagulation

Preoperative bridging with heparin (UFH or LMWH) is NOT recommended for most patients. 2, 3

• Bridging is only indicated for patients at very high thrombotic risk 2
• Routine bridging increases bleeding risk without reducing thrombotic complications 3
• The short half-life of apixaban (approximately 12 hours) makes bridging unnecessary in most cases 4

Biological Monitoring

Routine laboratory monitoring of apixaban levels is NOT necessary when recommended interruption periods are followed. 2

• Apixaban concentration and anti-Xa activity correlate well, but testing is not required for standard cases 5
• A prospective study demonstrated that 94% of patients achieved clinically insignificant apixaban concentrations (≤30 ng/mL) after appropriate discontinuation 5

Practical Implementation

Last Dose Timing

For a patient on apixaban 5 mg twice daily (standard dosing):

• If surgery is scheduled for 8 AM on Wednesday: The last dose should be taken on Monday morning (approximately 48 hours prior) 1
• For patients with impaired renal function: The last dose may need to be taken earlier (e.g., Saturday or Sunday for Wednesday surgery) 2

Documentation Requirements

Before proceeding, ensure you have:

• Current creatinine clearance calculation 2
• Complete medication list identifying P-gp and CYP3A4 inhibitors 2
• Patient age and weight 2
• Bleeding risk stratification of the planned procedure 1

Common Pitfalls to Avoid

Failing to assess renal function is the most critical error, as it directly impacts drug clearance and can lead to inadequate discontinuation time with increased bleeding risk 3

Unnecessary bridging with heparin products increases bleeding complications without providing thrombotic protection in most orthopedic surgery patients 3

Using a one-size-fits-all 48-hour hold without considering patient-specific factors (renal function, age, drug interactions) can result in either excessive anticoagulation at surgery or unnecessarily prolonged interruption 2

Proceeding with neuraxial anesthesia without confirming adequate drug clearance poses significant risk of spinal hematoma, particularly in elderly or renally impaired patients 2

Postoperative Resumption

• Apixaban can be resumed when adequate hemostasis is established, typically 12-24 hours after surgery 6, 1
• For immediate postoperative VTE prophylaxis, heparin or fondaparinux can be given at least 6 hours after the procedure 2, 6
• For hip replacement: Resume apixaban 2.5 mg twice daily for 35 days total 6, 1
• For knee replacement: Resume apixaban 2.5 mg twice daily for 12 days total 6, 1
• Monitor renal function postoperatively as surgical stress may affect kidney function and apixaban dosing requirements 2, 6