Perioperative Anticoagulation

Aka: Perioperative Anticoagulation, Anticoagulation in Surgical Patients, Surgical Patients on Anticoagulation, Coumadin Protocol for the Perioperative Period, Warfarin Protocol for the Perioperative Period, DOAC Protocol in the Perioperative Period, Bridge Therapy Protocol, Bridging Therapy

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II. Indications

  1. Patients on Anticoagulation undergoing surgery

III. Background

  1. Follow Decision Tree below for whether Bridging Therapy is required
    1. Based on surgical bleeding risk and Thromboembolism risk

IV. Efficacy: Perioperative Anticoagulation Bridging

  1. Bridging Risks outweigh benefits in patients with Venous Thromboembolism (esp. low risk of recurrence)
    1. Clark (2015) JAMA Intern Med 175(7): 1163-8 [PubMed]
  2. Atrial Fibrillation patients who are bridged have more adverse events (e.g. bleeding) without benefit
    1. Steinberg (2015) Circulation 131(5): 488-94 [PubMed]
    2. Carrier (2015) N Engl J Med 373(8): 697-704 [PubMed]

V. Precautions: Pitfalls

  1. Over Anticoagulation or premature use results in significantly increased bleeding complications
  2. Bleeding complications result in transfusions and stopping Anticoagulation which risks clots
  3. Direct Oral Anticoagulants or DOACs (e.g. Dabigatran, rivoroxaban)
    1. DOACs do not require bridging
    2. Delay surgery if possible for moderate-high risk of bleeding if high thrombosis risk
    3. Before surgery with low risk of bleeding, stop 1 day before surgery and restart the next day
    4. Before surgery with moderate risk of bleeding, stop 2 days before surgery and restart 2-3 days later
    5. Hold DOACs for 3-5 days before surgery if Creatinine Clearance <30 ml/min
    6. (2019) presc lett 26(10): 57
  4. Bridging protocol is recommended for only patients at high risk of thrombosis (as of 2015, BRIDGE Trial)
    1. See high risk indications as below
    2. Bridging does not appear to reduce thrombosis risk
    3. Bridging is associated with major bleeding complication in 2% of patients
    4. Clark (2015) JAMA Intern Med 175(7): 1163-8 +PMID:26010033 [PubMed]
  5. INR need not be normalized before most emergent, stabilization procedures
    1. INR should be normalized for sites sensitive to hemorrhagic pressure (e.g. CNS procedures, Lumbar Puncture)
    2. However elevated INR does not contradict most emergent procedures (esp. in compressible sites)
      1. Central Line
      2. Chest Tube
      3. Thoracentesis
      4. Paracentesis

VI. Protocol: Simplified Warfarin Bridging Protocol

  1. Day -7: Stop Aspirin (if appropriate), Obtain INR
  2. Day -5: Stop Warfarin, Check INR
  3. Day -3: Start Low Molecular Weight Heparin (LMWH) at full dose given every 12-24 hours
  4. Day -1:
    1. Stop or give half dose LMWH 12-24 hours before procedure
    2. Administer Vitamin K 1 mg PO if INR >1.5 (see normalization protocol below)
  5. Day 0: Surgery
    1. No LMWH
    2. Consider Fresh Frozen Plasma (FFP) if INR not at goal (see normalization protocol below)
    3. Restart Warfarin at 12-24 hours on evening of surgery (if adequate Hemostasis and approved by surgery)
  6. Day 1:
    1. Continue Warfarin (if started)
    2. Consider restarting LMWH per therapeutic or prophylactic dosing depending on bleeding risk
      1. Surgeon decides the time to restart LMWH or Heparin based on surgery bleeding risk
        1. Restart of Anticoagulation is modified for active bleeding, Thrombocytopenia and other complications
        2. LMWH (typically Enoxaparin or Lovenox) is preferred over Unfractionated Heparin for bridging
        3. Moderate-High thromboembolic risk (see below)
          1. Consider low dose prophylactic dosing of Heparin or LMWH until surgery allows full Anticoagulation
      2. Moderate to high bleeding risk procedure
        1. Avoid restarting therapeutic Heparin in first 48 hours, and until Hemostasis achieved
        2. May start Heparin or LMWH 48-72 hours after procedure (per surgeon discretion)
      3. Consult hematology for complex cases
      4. See below for how to choose dosing regimen
  7. Day 2-10: Obtain INR and stop LMWH when INR >2 for 2 consecutive days
    1. Anticipate by Day 5
    2. Use caution in postoperative Anticoagulation (risk of bleeding events)

VII. Protocol: Invasive procedures with Moderate to High Bleeding Risk

  1. Indications: Procedures with high bleeding risk
    1. Neurosurgery
    2. Cardiac Surgery or major thoracic surgery
    3. Abdominal or pelvic procedures
    4. Orthopedic joint procedures
    5. Major ENT or oral surgery
    6. Epidural Anesthesia
    7. Renal Biopsy
    8. Urologic Surgery
    9. Prolonged general Anesthesia with intubation (>45 minute procedure)
  2. DOAC Protocol (e.g. Dabigatran, rivoroxaban)
    1. DOACs are typically not bridged
      1. Delay procedure if possible, if transiently high thrombosis risk (e.g. recent Venous Thromboembolism)
    2. Hold DOAC 2 days before surgery and restart 2-3 days after surgery
      1. Stop DOAC 3-5 days before surgery if GFR <30 ml/min, impaired liver function or using strong CYP3A4 Inhibitor
      2. Hold Dabigatran (Pradaxa) for 4 days before surgery if GFR <50 ml/min
  3. Low risk for Thromboembolism (<4% risk/year)
    1. Indications
      1. Single Venous Thromboembolism >12 months prior and no other Hypercoagulable risk factors
      2. Chronic Atrial Fibrillation without stroke and CHADS2 score <3 (CHADS2Vasc <5)
      3. New bileaflet aortic Valve Replacement (St. Jude or Medtronic)
        1. No Atrial Fibrillation or other stroke risk
    2. Management
      1. No bridging with Perioperative Anticoagulation required
      2. Stop Warfarin 4-5 days before surgery
      3. Allow INR to normalize
      4. Post-operative DVT Prophylaxis if indicated
      5. Restart Warfarin postoperatively
  4. Intermediate risk for Thromboembolism (4-10% risk/year)
    1. Indications
      1. Atrial Fibrillation with CHADS-2 Score 3-4 (CHADS2Vasc 5-7)
      2. Venous Thromboembolism in the last 3-12 months
      3. Recurrent Venous Thromboembolism
      4. Active cancer (treated in the last 6 months or on palliative cancer management)
      5. Non-severe Thrombophilia (e.g. Heterozygous Factor V Leiden, Prothrombin gene mutation)
      6. Bileaflet aortic Valve Replacement and at least one risk factor
        1. Atrial Fibrillation
        2. Prior Cerebrovascular Accident or TIA
        3. Hypertension
        4. Diabetes Mellitus
        5. Congestive Heart Failure
        6. Age >75 years old
    2. Management
      1. Stop Warfarin 4-5 days before surgery
      2. Allow INR to decrease
      3. Start Anticoagulation 2 days before surgery
        1. Low dose Heparin 5000 U SC or
        2. Low Molecular Weight Heparin at prophylactic doses
      4. Restart low dose Heparin or LMWH postoperatively (hold for 24-48 hours postoperatively)
      5. Restart Warfarin immediately postoperatively
  5. High risk for Thromboembolism (>10% risk/year)
    1. Indications
      1. Venous Thromboembolism (PE, DVT) within last 3 months
      2. Cardiac Thromboembolism (any cause) within 1 month
      3. Cerebrovascular Accident or TIA in the last 6 months
      4. Atrial Fibrillation with one or more additional risks (only 3% of Atrial Fibrillation is high risk)
        1. CHADS-2 Score 5 or CHADS2-VASc Score 7 or higher
        2. Cerebrovascular Accident (CVA) in last 3 months or
        3. Rheumatic Valvular Disease
      5. Strong Thrombophilia
        1. Two or more Thrombophilia risks
        2. Active cancer associated with high VTE Risk
        3. Antiphospholipid Antibody Syndrome (uncommon)
        4. Antithrombin III Deficiency (rare)
        5. Protein C Deficiency
        6. Protein S Deficiency
      6. Mechanical Heart Valves
        1. Mitral Valve Replacement (any)
        2. Caged-Ball, Tilting disc or other older aortic Valve Replacement
        3. Higher risks
          1. Comorbidity (e.g. Congestive Heart Failure)
          2. Atrial Fibrillation with mechanical valve
        4. Exceptions: Lower risks (not needing bridging)
          1. New aortic valves (see above)
    2. Management
      1. See Bridging protocol above
      2. Stop Warfarin 4-5 days before surgery
      3. Allow INR to decrease
      4. Start Anticoagulation 2 days before surgery
        1. Full dose Heparin or
        2. Full dose Low Molecular Weight Heparin
      5. Hold Heparin before surgery
        1. Hold Heparin IV for 4-5 hours before surgery
        2. Hold LMWH for 12-24 hours before surgery
      6. Restart Heparin after procedure
      7. Restart Warfarin postoperatively

VIII. Protocol: Procedures with Low Risk of Bleeding

  1. Procedures
    1. Abdominal Hernia repair
    2. Arthroscopy
    3. Gynecologic Surgery
    4. Endoscopy with biopsy (e.g. Colonoscopy)
    5. Bronchoscopy
    6. Coronary angiogram
    7. Hemorrhoidal Surgery
    8. Hysterectomy
    9. Laparoscopic Cholecystectomy
    10. Lymph Node biopsy
  2. Protocol
    1. DOACs (e.g. Dabigatran, rivoroxaban)
      1. Hold DOAC one day before surgery and restart 1 day after surgery
      2. Hold Dabigatran (Pradaxa) for 3 days before surgery if GFR <50 ml/min
      3. Stop DOAC 3 days before surgery if GFR <30 ml/min, impaired liver function or using strong CYP3A4 Inhibitor
    2. Warfarin
      1. Lower Warfarin dose 4 to 5 days before surgery
      2. Target INR of 1.3 to 1.5 before surgery
      3. Restart Warfarin at regular dosing after surgery
      4. Consider adjunctive Heparin at 5000 U SC post-op

IX. Protocol: Very Low Risk of Bleeding

  1. Procedures
    1. Dental procedures (dental extraction, restoration, endodontic surgery)
    2. Cataract Surgery
    3. Minor Dermatologic procedures
    4. Pacemaker and IACD placement
    5. Endoscopy without biopsy
  2. Protocol
    1. DOACs (e.g. Dabigatran, rivoroxaban)
      1. Hold DOAC on day of surgery and restart 4-6 hours after procedure
    2. Warfarin
      1. Continue Warfarin at current dose
      2. Keep INR < 3.0 (or <3.5 by some protocols)
      3. Only discontinue Warfarin for high bleeding risk
    3. Consider local bleeding control if needed (dental)
      1. Tranexamic Acid soaked gauze or pledgets
      2. Additional Sutures
      3. Gelatin sponges
      4. Epsilon aminocaproic acid (Amicar) mouthwash (discuss with hematology and surgeon)

X. Protocol: Normalization of INR after stopping Warfarin

  1. Anticipate INR normalization after stopping for 4 days
    1. Bleeding risk is low when INR <1.5
  2. Indications for transiently stopping Coumadin
    1. Prolonged INR
    2. Surgery
  3. Factors predicting delayed INR decrease
    1. Advanced age (80 years or older)
    2. Coumadin sensitive (maintenance dose <15 mg/week)
    3. Decompensated Congestive Heart Failure
    4. Active malignancy
    5. Liver disease
    6. Concurrent medications that potentiate Coumadin
      1. See Coumadin Drug Interactions
  4. Options for reversal
    1. Vitamin K (preferred if >12 hours pre-operative)
      1. Time to surgery >24 hours
        1. Vitamin K 1.0-2.5 mg PO one dose
        2. Maximum Vitamin K dose: 5 mg (risk of resistance)
      2. Time to surgery 12-24 hours
        1. Vitamin K 0.5 mg IV slow infusion one dose
    2. Clotting Factor replacement (within 12 hours)
      1. Fresh Frozen Plasma (FFP) 15 ml/kg
  5. Example Protocol
    1. PM prior to surgery: Vitamin K 1-2.5 mg PO x1 dose
    2. AM of surgery: FFP if INR >1.5
    3. Post-operatively (12-24 hours): Anticoagulate
      1. See protocols above for agents and dosing

XI. Resources

  1. Oral Anticoagulant Medications and Dental Procedures
    1. https://www.ada.org/resources/research/science-and-research-institute/oral-health-topics/oral-anticoagulant-and-antiplatelet-medications-and-dental-procedures

XII. References

  1. Dummer (2009) Perioperative Guidelines
  2. Ansell (2001) Chest 119(1 Suppl): 22S-38S [PubMed]
  3. Douketis (2008) Chest 133(6 Suppl):299S-339S [PubMed]
  4. Douketis (2022) Chest 162(5):e207-43 +PMID: 35964704 [PubMed]
  5. Hylek (2001) Ann Intern Med 135:393-400 [PubMed]

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