When is warfarin (coumarin) indicated and how is it dosed?

Warfarin Indications and Dosing

Warfarin is indicated for prevention and treatment of venous thromboembolism, atrial fibrillation, and mechanical heart valves, with dosing individualized based on INR monitoring targeting 2.0-3.0 for most indications. 1, 2

Primary Indications for Warfarin

• Venous Thromboembolism (DVT/PE):

  • First episode secondary to transient risk factor: 3 months treatment 1
  • First episode idiopathic: 6-12 months treatment 1
  • Two or more episodes: indefinite treatment 1
  • With thrombophilic conditions: 12 months to indefinite treatment 1

• Atrial Fibrillation:

  • Non-valvular AF with high stroke risk (prior stroke/TIA, age >75, heart failure, hypertension, diabetes) 1
  • Valvular AF, especially with mitral stenosis 1
  • Target INR: 2.0-3.0 1, 3

• Mechanical Heart Valves:

  • Higher target INR may be required (2.5-3.5) depending on valve type and position 2

Dosing Protocol

Initial Dosing:

1. Starting dose: Typically 2-5 mg daily for most patients 3
2. Monitoring: Check INR within 2-7 days after starting therapy 3
3. Frequency: Monitor INR daily until therapeutic range (2.0-3.0) is reached and sustained for 2 consecutive days 3

Dose Adjustments:

• INR < 2.0: Increase dose by 10-20% 3
• INR > 3.0: Decrease dose by 10% 3
• Stable INR: Maintain current dose 3

Maintenance Monitoring:

• Once stable, check INR every 4 weeks 3
• Time in Therapeutic Range (TTR) should be maintained above 60% for optimal outcomes 4

Special Considerations

Perioperative Management:

For patients requiring surgery:

1. Low bleeding risk procedures: Stop warfarin 5 days before procedure 2
2. High bleeding risk procedures: Stop warfarin 5-6 days before procedure 2
3. Bridging anticoagulation:
   • High thrombotic risk: Use therapeutic LMWH (e.g., enoxaparin 1.5 mg/kg once daily or 1.0 mg/kg twice daily) 2
   • Moderate risk: Use prophylactic LMWH (e.g., enoxaparin 40 mg daily) 2
   • Low risk: No bridging needed 2
4. Resumption: Resume warfarin evening of or morning after procedure 2

Pregnancy:

• Warfarin is contraindicated during pregnancy, especially first trimester (risk of embryopathy) 2
• LMWH is preferred during pregnancy 2

Cancer Patients:

• Cancer patients have higher risk of recurrent thrombosis despite adequate anticoagulation 3
• LMWH is preferred over warfarin in active cancer 2, 3

Management of Excessive Anticoagulation

• INR > 3.0 but < 5.0 (no bleeding): Reduce dose or omit next dose 3
• INR > 5.0 (no bleeding): Hold warfarin, consider vitamin K 1-2 mg orally 3
• Life-threatening bleeding: Administer vitamin K 5-10 mg IV plus prothrombin complex concentrate 3

Common Pitfalls

1. Drug interactions: Numerous medications affect warfarin metabolism, including antibiotics, antifungals, and many herbal supplements 5

2. Diet fluctuations: Inconsistent vitamin K intake can cause INR variability 3

3. Inadequate monitoring: Failure to maintain TTR >60% increases thrombotic and bleeding risks 4

4. Inappropriate bridging: Unnecessary bridging increases bleeding risk; individualize based on thrombotic and bleeding risk 2

5. Excessive INR: INR >6.0 significantly increases major hemorrhage risk (4.4% within 14 days) 6

Warfarin management requires careful attention to drug interactions, dietary habits, and regular INR monitoring to maintain therapeutic efficacy while minimizing bleeding complications.