What is the recommended approach to interrupting direct oral anticoagulants before operative or invasive procedures based on bleeding risk and renal function?

Perioperative DOAC Management

For elective surgery, stop DOACs based on bleeding risk and renal function without heparin bridging: 1 day before low-risk procedures and 2–3 days before high-risk procedures, then resume 1–3 days postoperatively once hemostasis is secure. 1

Risk Stratification Framework

High Bleeding Risk Procedures

• Major surgery with extensive tissue injury, cancer resection, major orthopedic surgery (hip/knee replacement), cardiac/intracranial/spinal surgery, urologic or GI surgery with anastomosis, and any procedure >45 minutes duration 2
• Neuraxial anesthesia (spinal/epidural) is classified as high-risk due to catastrophic consequences of bleeding 2

Low-to-Moderate Bleeding Risk Procedures

• Arthroscopy, colonoscopy with biopsy, abdominal hernia repair, dental extractions (1–3 teeth), cataract surgery, pacemaker/ICD implantation 2, 1

Minimal Bleeding Risk Procedures

• Minor dermatologic procedures, dental cleanings, simple fillings—these can often proceed without interruption 2

DOAC Interruption Protocol

Factor Xa Inhibitors (Rivaroxaban, Apixaban, Edoxaban)

For patients with CrCl >30 mL/min:

• Low-risk procedures: Stop 1 day (24 hours) before surgery 1, 3
• High-risk procedures: Stop 2–3 days (48–72 hours) before surgery 1, 3
• Very high hemorrhagic-risk surgeries (intracranial, neuraxial): Extend to 5 days 1

For patients with CrCl 30–50 mL/min:

• Add 1 additional day to the interruption period for high-risk procedures 1

Dabigatran (Renal-Function Dependent)

CrCl >50 mL/min:

• Low-risk procedures: Stop 1–2 days before 4, 1
• High-risk procedures: Stop 4 days before 1, 4

CrCl 30–50 mL/min:

• Low-risk procedures: Stop 2 days before 1
• High-risk procedures: Stop 5 days before 1, 4

CrCl <30 mL/min:

• Extend interruption to 3–5 days for any invasive procedure 4

Special Considerations for Extended Interruption

• Age >80 years, concomitant P-glycoprotein inhibitors (all DOACs), or CYP3A4 inhibitors (rivaroxaban, apixaban, edoxaban) warrant longer pre-operative interruption 1
• Neuraxial procedures require 72 hours minimum for apixaban/rivaroxaban/edoxaban and 4–5 days for dabigatran to prevent catastrophic spinal hematoma 1, 5

Bridging Anticoagulation: NOT Recommended

Pre-operative bridging with UFH or LMWH is contraindicated for DOACs. 1, 3

• Bridging increases major bleeding risk without reducing thrombotic events 1
• The PAUSE trial demonstrated 0.16% arterial thromboembolism and 1.35% major bleeding rates without bridging 6
• Retrospective analyses show bridging confers 2–5% major bleeding rates with no thrombotic benefit 6
• Exception: Reserve bridging only for mechanical mitral valves, stroke within the past month, or recent VTE <3 months with thrombophilia—and only after multidisciplinary review 1, 6

Postoperative Resumption

Low-to-Moderate Risk Procedures

• Resume DOACs 24 hours after surgery once adequate hemostasis is confirmed 1, 3
• For minimal-risk procedures, resumption as early as 6 hours is acceptable 1, 6

High Bleeding Risk Procedures

• Resume DOACs 48–72 hours after surgery 1, 3
• Consider reduced-dose DOAC (e.g., apixaban 2.5 mg BID) for the first 2–3 days in high thrombotic-risk patients, then transition to full dose 6
• If therapeutic anticoagulation must be delayed beyond 48 hours, use prophylactic-dose LMWH until full-dose DOAC can be safely restarted 6

Timing by Regimen

• Twice-daily DOACs: Resume the evening of surgery day if ≥6 hours elapsed 1
• Once-daily morning regimens: Resume the next morning 1
• Once-daily evening regimens: Resume the same evening if ≥6 hours elapsed 1

Laboratory Monitoring

Routine coagulation testing (INR, aPTT) is not recommended when standardized interruption protocols are followed 1, 5

• INR and aPTT are insensitive to residual DOAC levels and should not guide management 6
• DOAC-specific anti-factor Xa assays are more sensitive but add little value in elective settings with proper timing 6, 7
• Consider DOAC level measurement only for emergent/urgent surgery (<24 hours), severe renal impairment, or uncertainty about drug clearance 3, 7

Emergent and Urgent Surgery

For emergent surgery (<6 hours) or urgent surgery (6–24 hours):

• Bleeding rates reach up to 23% and thromboembolism up to 11% 3
• Delay surgery for 1–2 half-lives if possible 8
• Use reversal agents when DOAC levels are elevated or unavailable:
  • Idarucizumab for dabigatran 4, 3
  • Andexanet-α or prothrombin complex concentrate (PCC) 50 IU/kg for factor Xa inhibitors 5, 3

Critical Pitfalls to Avoid

• Never bridge DOACs with heparin—this markedly raises bleeding risk without thrombotic protection 1, 6
• Never perform neuraxial anesthesia if residual DOAC levels may be present, especially in elderly or renally impaired patients 1, 5
• Do not proceed with surgery if INR >1.5 in warfarin-treated patients 1
• Do not overlook drug interactions (P-glycoprotein or CYP3A4 inhibitors) that prolong DOAC clearance 1
• Do not resume therapeutic anticoagulation before adequate hemostasis—early LMWH (<24 hours) after major surgery confers up to 20% major bleeding risk 2, 6
• Do not use INR or aPTT to assess DOAC activity—these tests are unreliable for DOACs 6, 5
• If traumatic neuraxial puncture occurs, delay the next DOAC dose for at least 48 hours 5