When should apixaban (Direct Oral Anticoagulant) be stopped before an epidural procedure to minimize bleeding risk?

When to Stop Apixaban Before Epidural Procedures

For epidural procedures, apixaban must be stopped for at least 5 days (120 hours) prior to the procedure in patients with normal renal function, as neuraxial anesthesia/puncture carries very high hemorrhagic risk with potentially catastrophic consequences of epidural hematoma. 1

Risk Classification

Epidural procedures are classified as very high hemorrhagic risk procedures because:

• Bleeding in the confined epidural space can cause spinal cord compression 1
• Surgical hemostasis cannot be performed in this location 1
• Epidural hematoma can result in permanent paralysis if not immediately recognized and surgically decompressed 2

Discontinuation Timeline Based on Renal Function

Normal Renal Function (CrCl ≥80 mL/min)

• Stop apixaban 5 days (120 hours) before epidural procedure 1
• This extended window accounts for the very high bleeding risk and inability to control hemorrhage in the epidural space 1

Impaired Renal Function (CrCl 50-79 mL/min)

• Stop apixaban 5 days before procedure 1
• No adjustment needed compared to normal renal function for apixaban specifically 1

Moderate Renal Impairment (CrCl 30-49 mL/min)

• Stop apixaban 5 days before procedure 1
• Consider biological monitoring of drug levels if available 1

Severe Renal Impairment (CrCl 15-29 mL/min)

• Stop apixaban at least 5 days before procedure 1
• Strongly consider measuring apixaban levels before proceeding 1

Critical Safety Warnings

The French Working Group on Perioperative Hemostasis strongly recommends NOT performing spinal or epidural anesthesia in patients with possible residual DOAC concentration (insufficient discontinuation time). 1

This warning is particularly emphasized for:

• Patients over 80 years of age 1
• Patients with renal failure 1
• Any patient where adequate discontinuation time cannot be confirmed 1

Additional Risk Factors Requiring Extended Cessation

Consider extending the cessation period beyond 5 days if the patient has:

• P-glycoprotein inhibitors (e.g., verapamil, amiodarone, dronedarone) - these increase apixaban levels 1
• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir) - these increase apixaban exposure 1, 3
• Age >80 years - reduced drug clearance 1
• Body weight <60 kg - higher drug concentrations 3

Comparison to Standard Surgical Procedures

This 5-day cessation for epidural procedures is significantly longer than for standard high-risk surgeries:

• High-risk surgeries typically require only 48 hours cessation with normal renal function 1, 4
• The FDA label recommends 48 hours for moderate-to-high bleeding risk procedures 3
• However, neuraxial procedures are specifically categorized as requiring extended cessation 1

Bridging Anticoagulation

No bridging with heparin or low-molecular-weight heparin is recommended during the cessation period, except in very high thrombotic risk patients 1

The rationale:

• Bridging increases bleeding risk without proven benefit for DOACs 1
• The rapid offset of apixaban makes bridging unnecessary in most cases 4

Biological Monitoring Considerations

While not routinely required, consider measuring apixaban levels if:

• The procedure cannot be delayed and adequate cessation time is uncertain 1
• Patient has severe renal impairment 1
• Patient is on interacting medications 1
• Anti-factor Xa levels (DOAC-calibrated) can measure residual apixaban activity 4, 5

Resumption After Epidural Procedure

Resume apixaban 48-72 hours after the procedure once adequate hemostasis is established 1, 4

Critical considerations for resumption:

• If an epidural catheter remains in place, therapeutic anticoagulation must NOT be resumed until after catheter removal 1
• Use prophylactic heparin (UFH or LMWH) if thromboprophylaxis is needed while catheter is in place 1
• Resume therapeutic apixaban only 12 hours after the last prophylactic LMWH dose 1

Common Pitfalls to Avoid

1. Do not use the standard 48-hour cessation window recommended for other high-risk surgeries - epidural procedures require 5 days 1

2. Do not proceed if patient cannot confirm last dose timing - residual anticoagulation with epidural hematoma can cause permanent paralysis 1, 2

3. Do not forget to check renal function - use Cockcroft-Gault formula for creatinine clearance calculation 1

4. Do not overlook drug interactions - P-gp and CYP3A4 inhibitors significantly prolong apixaban half-life 1, 3

5. Do not resume therapeutic anticoagulation with epidural catheter in place - this dramatically increases hematoma risk 1

Recognition of Epidural Hematoma

If epidural hematoma occurs, diagnosis is based on:

• Severe pain at the injection site 2
• Rapid neurological deterioration 2
• Urgent MRI confirmation 2
• Immediate surgical decompression is required to prevent permanent neurological sequelae 2