What is the recommended guideline for holding Direct Oral Anticoagulants (DOACs) such as apixaban, rivaroxaban, dabigatran, and edoxaban prior to surgery?

Guideline for Holding DOACs Prior to Surgery

For elective surgery, stop DOACs 1 day before low-to-moderate bleeding risk procedures and 2 days before high bleeding risk procedures in patients with normal renal function, with no DOAC taken on the day of surgery. 1

Preoperative Management by Bleeding Risk

Low-to-Moderate Bleeding Risk Procedures

• Stop all DOACs (apixaban, rivaroxaban, edoxaban) 1 day before surgery (skip 2-3 doses depending on dosing frequency) 1
• Stop dabigatran 1-2 days before surgery if creatinine clearance (CrCl) ≥50 mL/min 1
• Examples include: cholecystectomy, inguinal hernia repair, colonoscopy with biopsy, arthroscopy 1, 2
• No DOAC should be taken on the day of surgery 1

High Bleeding Risk Procedures

• Stop apixaban, rivaroxaban, and edoxaban 2 days before surgery (skip 4-5 doses) 1, 3
• Stop dabigatran 2 days before surgery if CrCl ≥50 mL/min 1
• Examples include: cardiac surgery, intracranial/spinal surgery, major abdominal surgery, major cancer surgery, joint replacement 1, 4, 2

Very High Bleeding Risk Procedures

• For intracranial neurosurgery or neuraxial anesthesia/puncture, extend interruption up to 5 days for all DOACs in patients without renal failure 1
• Consider biological monitoring of DOAC levels if needed 1

Special Considerations for Renal Impairment

Dabigatran (80% renal clearance)

• CrCl 30-50 mL/min: Stop 3-4 days before high bleeding risk surgery 1, 5
• CrCl <30 mL/min: Stop 4-5 days before surgery 1, 5
• Dabigatran requires the longest interruption due to predominant renal elimination 1

Factor Xa Inhibitors (Apixaban, Rivaroxaban, Edoxaban)

• CrCl ≥50 mL/min: Standard interruption times apply 1
• CrCl 30-50 mL/min: Consider extending interruption by 1 additional day 1
• Apixaban has only 25% renal clearance, making it less dependent on kidney function 4, 2

Additional Risk Factors Requiring Longer Interruption

Extend DOAC interruption in patients with: 1

• Severely impaired renal function (CrCl <30 mL/min)
• Severely impaired hepatic function
• Concomitant use of P-glycoprotein inhibitors (affects all DOACs)
• Concomitant use of CYP3A4 inhibitors (affects apixaban, rivaroxaban, edoxaban)
• Age >80 years (particularly for dabigatran) 1

Bridging Anticoagulation

Preoperative bridging with heparin or low-molecular-weight heparin is NOT recommended for routine DOAC interruption 1, 2

• The rapid offset of DOACs eliminates the need for bridging 4
• Bridging may only be considered in very high thrombotic risk patients 1

Postoperative Resumption

Low-to-Moderate Bleeding Risk

• Resume DOACs 1 day after surgery (24 hours postoperatively) at usual dose 1
• Ensure adequate hemostasis before resumption 1, 3

High Bleeding Risk

• Resume DOACs 2-3 days after surgery (48-72 hours postoperatively) 1, 4, 2
• Consider reduced dose (e.g., apixaban 2.5 mg twice daily) for first 2-3 days in high thrombotic risk patients 4, 2
• May use prophylactic LMWH starting 6 hours postoperatively until therapeutic DOAC resumed 1

Laboratory Monitoring

Routine coagulation testing (INR, aPTT) is NOT required when recommended interruption periods are followed 1

Consider DOAC-specific testing in urgent surgery (<24 hours): 1, 4

• DOAC-calibrated anti-factor Xa levels for apixaban, rivaroxaban, edoxaban
• Dilute thrombin time or ecarin clotting time for dabigatran
• Standard PT/aPTT may be insensitive to residual DOAC effect 1, 4

Critical Pitfalls to Avoid

• Never perform neuraxial anesthesia with possible residual DOAC concentration, especially in dabigatran patients >80 years or with renal impairment 1
• Do not double the dose to make up for a missed preoperative dose 3, 5
• Verify recent creatinine clearance before determining interruption timing, as renal function affects clearance 1
• Check for drug interactions with P-glycoprotein or CYP3A4 inhibitors that may prolong DOAC effect 1
• Ensure at least 6 hours elapsed before any postoperative DOAC resumption 1