Summary: Perioperative Management of Patients Taking Direct Oral Anticoagulants

Direct oral anticoagulants (DOACs)—including apixaban, rivaroxaban, edoxaban, and dabigatran—are increasingly used for stroke prevention in atrial fibrillation and for treating venous thromboembolism. Effective perioperative management of DOACs is essential to minimize bleeding and thromboembolic risks during surgical and nonsurgical procedures. Below are practical recommendations focused on the perioperative management of patients taking DOACs, based on a recent JAMA review article.

Elective Surgical or Nonsurgical Procedures

Classify Bleeding Risk of Procedures:

1. Minimal Risk:
   • Minor dental procedures (e.g., cleaning, extractions)
   • Minor dermatologic procedures (e.g., skin lesion removal)
   • Cataract surgery
2. Low to Moderate Risk:
   • Endoscopic procedures without high-risk interventions
   • Cholecystectomy
   • Inguinal hernia repair
3. High Risk:
   • Major surgery (e.g., cancer surgery, joint replacement)
   • Procedures involving neuraxial anesthesia
   • Endoscopic procedures with high-risk interventions (e.g., large polyp removal)

DOAC Management Strategies:

1. Minimal Bleeding Risk Procedures:
   • Option 1: Continue DOACs without interruption.
   • Option 2: For added safety, withhold the morning dose on the day of the procedure (especially for twice-daily DOACs like apixaban and dabigatran).
2. Low to Moderate Bleeding Risk Procedures:
   • Preoperative:
     • Discontinue DOACs 1 day before the procedure.
     • This allows approximately 2 half-lives for drug clearance.
   • Postoperative:
     • Resume DOACs 1 day after the procedure, ensuring adequate hemostasis.
3. High Bleeding Risk Procedures:
   • Preoperative:
     • Discontinue DOACs 2 days before the procedure.
     • This allows approximately 4-5 half-lives for drug clearance.
   • Postoperative:
     • Resume DOACs 2-3 days after the procedure, based on bleeding risk and hemostasis.

Evidence Supporting These Strategies:

• The PAUSE study demonstrated that standardized interruption protocols without heparin bridging result in low rates of:
  • Thromboembolism: 0.2%–0.4%
  • Major Bleeding: 1%–2%

Postoperative DOAC Resumption:

• Assess surgical-site hemostasis before resuming DOACs.
• Delay resumption if there is ongoing bleeding or concerns about hemostasis.
• For high bleeding risk procedures, consider a longer delay (2–3 days).

Perioperative Heparin Bridging:

• Not recommended for patients on DOACs.
• Bridging increases bleeding risk without reducing thromboembolism.
• DOACs have rapid offset and onset, making bridging unnecessary.

Special Considerations

Patients with Impaired Renal Function:

• For CrCl 30–50 mL/min:
  • Dabigatran: Extend preoperative discontinuation by an additional day.
• For CrCl <30 mL/min:
  • Dabigatran is contraindicated.
  • For other DOACs, consider extending discontinuation to 3–4 days before surgery.

Patients Undergoing Neuraxial Anesthesia:

• Discontinue DOACs for 3 days (apixaban, edoxaban, rivaroxaban) or 4 days (dabigatran) before the procedure.
• Minimizes risk of spinal or epidural hematoma.

Dental Procedures:

• Generally safe to continue DOACs.
• For added safety:
  • Omit or delay the dose on the day of the procedure.
  • Employ local hemostatic measures (e.g., tranexamic acid mouthwash).

Endoscopic Procedures:

• Low-risk procedures (e.g., diagnostic endoscopy without biopsy):
  • Follow standard DOAC interruption for low to moderate bleeding risk.
• High-risk procedures (e.g., polypectomy of large polyps):
  • Extend DOAC discontinuation by an additional day pre- and post-procedure.

Patients Unable to Resume Oral Medications Postoperatively:

• Use prophylactic low-molecular-weight heparin (LMWH) until oral intake is possible.
• Avoid therapeutic-dose LMWH due to bleeding risk.

Emergent, Urgent, or Semiurgent Procedures

Risks:

• Higher bleeding risk: Up to 23%
• Thromboembolism risk: Up to 11%

Management Strategies:

1. Assess Time Since Last DOAC Dose:
   • If within 48 hours, consider that significant anticoagulant effect may persist.
2. Laboratory Testing (if available):
   • DOAC Level Testing:
     • ≥50 ng/mL: Consider using reversal agents.
     • <50 ng/mL: May proceed without reversal agents.
3. Use of Reversal Agents:
   • For Dabigatran:
     • Idarucizumab (5 g IV)
   • For Factor Xa Inhibitors (apixaban, rivaroxaban, edoxaban):
     • Andexanet alfa (dosing based on last dose timing and amount)
     • Prothrombin Complex Concentrates (PCCs): If andexanet alfa is unavailable or contraindicated.
4. Proceeding Without Testing:
   • If testing is unavailable and last DOAC dose was within 48 hours, consider reversal agents.
   • If >48 hours since last dose, may proceed without reversal.

Considerations:

• Reversal agents are expensive and may carry thrombotic risks.
• Use should be judicious, weighing risks and benefits.
• Consult hematology or thrombosis experts when possible.

Key Takeaways

• Elective Procedures:
  • Utilize standardized protocols based on procedural bleeding risk.
  • Routine preoperative DOAC level testing is unnecessary.
  • Avoid heparin bridging.
• Emergent/Urgent Procedures:
  • Reversal agents may be appropriate when significant DOAC levels are present.
  • Decision to use reversal agents should consider bleeding risk, time since last dose, and availability of DOAC level testing.
• Patient Communication:
  • Ensure patients understand the plan for DOAC interruption and resumption.
  • Provide clear instructions regarding timing and dosing.
• Interdisciplinary Coordination:
  • Collaborate with surgical teams, anesthesiologists, and pharmacists.
  • Use electronic medical records and clinical decision support tools to enhance communication.

Conclusion

By applying standardized perioperative management protocols, clinicians can effectively balance the risks of bleeding and thromboembolism in patients taking DOACs who require surgical or nonsurgical procedures. These strategies simplify decision-making, avoid unnecessary interventions like heparin bridging, and promote patient safety.

Reference: Douketis JD, Spyropoulos AC. Perioperative Management of Patients Taking Direct Oral Anticoagulants: A Review. JAMA. 2024;332(10):825–834. doi:10.1001/jama.2024.12708