How should warfarin, direct oral anticoagulants, and antiplatelet agents be discontinued before a moderate‑to‑high bleeding‑risk invasive procedure, and when is bridging with therapeutic low‑molecular‑weight heparin indicated?

Perioperative Anticoagulation Management for Moderate-to-High Bleeding Risk Procedures

Warfarin Management

Stop warfarin 5 days (five doses) before moderate-to-high bleeding risk procedures, with bridging therapy reserved only for patients at highest thrombotic risk. 1

Discontinuation Protocol

• Warfarin should be stopped 5 days prior to surgery to allow adequate clearance (half-life 36-42 hours). 1
• Check INR on the day of procedure; postpone surgery if INR >1.5. 1
• For urgent reversal, administer low-dose vitamin K (2.5-5.0 mg) IV or oral, plus fresh-frozen plasma or prothrombin complex concentrate for immediate effect. 1

Bridging Indications (High Thrombotic Risk Only)

Bridging with therapeutic-dose LMWH is indicated only for patients with:

• Mechanical prosthetic heart valves 1
• Atrial fibrillation with very high stroke risk 1
• Recent venous thromboembolism (<3 months) plus thrombophilia 1
• Biological prosthetic valves or mitral valve repair within 3 months 1

Bridging Protocol When Indicated

• Start LMWH 2 days after warfarin discontinuation (1 day after acenocoumarol). 1
• Use therapeutic dosing: 70 U/kg anti-factor Xa twice daily for high-risk patients. 1
• Administer last LMWH dose at least 12 hours before the procedure. 1
• For mechanical valves, some centers use IV UFH until 4 hours before surgery. 1

Postoperative Resumption

• Resume LMWH 1-2 days after surgery (at least 12 hours post-procedure) depending on hemostatic status. 1
• Restart warfarin on day 1-2 post-surgery with maintenance dose plus 50% boost for two consecutive days. 1
• Continue LMWH until INR returns to therapeutic range. 1

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Direct Oral Anticoagulants (DOACs) Management

For moderate-to-high bleeding risk procedures, stop DOACs 3 days before surgery for rivaroxaban/apixaban/edoxaban, and 4-5 days for dabigatran based on renal function—bridging with heparin is NOT recommended. 1, 2, 3

Rivaroxaban, Apixaban, and Edoxaban

• Stop 3 days before the procedure when creatinine clearance >30 mL/min. 1, 4, 2
• These agents have similar pharmacokinetics allowing uniform management. 1
• Extended interruption (up to 5 days) for very high hemorrhagic risk procedures like intracranial neurosurgery or neuraxial anesthesia. 1

Dabigatran (Renal Function-Dependent)

• CrCl >50 mL/min: Stop 4 days before procedure 1, 2
• CrCl 30-50 mL/min: Stop 5 days before procedure 1, 2
• Dabigatran's predominant renal elimination requires longer interruption in renal impairment. 1

Critical Factors Requiring Extended Interruption

• Age >80 years 1, 4
• Concomitant P-glycoprotein inhibitors (all DOACs) 1, 4
• Concomitant CYP3A4 inhibitors (rivaroxaban, apixaban, edoxaban) 1, 4

No Bridging Anticoagulation

Preoperative bridging with UFH or LMWH is NOT recommended for DOACs. 1, 2 Recent evidence demonstrates that bridging increases bleeding risk without reducing thrombotic events. 1, 2

Postoperative Resumption

• Resume DOACs at least 6 hours after procedure if adequate hemostasis achieved. 1, 5, 2, 3
• For twice-daily regimens: resume evening of procedure day. 1, 5
• For once-daily morning regimens: resume next morning. 1
• For once-daily evening regimens: resume same evening if >6 hours post-procedure. 1
• Delay resumption and use prophylactic anticoagulation if ongoing bleeding or surgical contraindication exists. 1, 2

Biological Monitoring

• Routine coagulation monitoring is NOT required when recommended interruption periods are followed. 1, 4
• Consider monitoring only for very high hemorrhagic risk procedures or patients with drug accumulation risk factors. 4

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Antiplatelet Agents Management

Continue aspirin through most moderate-to-high bleeding risk procedures; stop clopidogrel/ticagrelor 7-10 days before surgery except in patients with recent coronary stents or acute coronary syndrome. 6

Aspirin

• Continue low-dose aspirin for most surgical procedures. 6
• Discontinue only for procedures where bleeding occurs in closed spaces (intracranial, spinal canal, posterior eye chamber) or when excessive blood loss expected. 6
• The thrombotic risk of aspirin withdrawal exceeds surgical bleeding risk in most cases. 6

Clopidogrel/Ticagrelor (P2Y12 Inhibitors)

• Stop 7-10 days before high bleeding risk procedures in patients without recent coronary events. 1, 6, 7
• Do NOT discontinue if prescribed for acute coronary syndrome or during stent re-endothelialization. 6
• For elective procedures, postpone surgery until the end of the indication period for dual antiplatelet therapy. 6
• Resume within 12-24 hours post-procedure. 6

Patients with Coronary Stents

• Bare-metal stents: Avoid elective surgery within 6 weeks of placement. 1
• Drug-eluting stents: Avoid elective surgery within 6 months of placement. 1
• If surgery cannot be delayed, continue dual antiplatelet therapy despite bleeding risk. 1, 6

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Common Pitfalls to Avoid

Critical Errors

• Never bridge DOACs with heparin—this dramatically increases bleeding without reducing thrombosis. 1, 5, 2
• Never perform neuraxial anesthesia with possible residual DOAC levels, especially in elderly or renally impaired patients. 1
• Never routinely bridge warfarin—reserve only for highest thrombotic risk patients. 1
• Never stop antiplatelet agents in patients with recent coronary stents or ACS—thrombotic risk overwhelms bleeding risk. 6

Timing Errors

• Do not use uniform DOAC interruption periods—dabigatran requires renal function-based adjustment. 1, 2
• Do not resume full-dose anticoagulation too early—wait minimum 6 hours and confirm hemostasis. 1, 2, 3
• Do not give last LMWH dose <12 hours before procedure when bridging warfarin. 1

Assessment Errors

• Do not proceed with surgery if INR >1.5 in warfarin patients. 1
• Do not ignore drug interactions (P-glycoprotein, CYP3A4 inhibitors) that prolong DOAC clearance. 1, 4
• Do not assume elderly patients clear warfarin normally—decay may be delayed. 1