What is the recommended dosage of warfarin (International Normalized Ratio (INR) antagonist) for the treatment of Deep Vein Thrombosis (DVT)?

Warfarin Dosing for Deep Vein Thrombosis (DVT)

For patients with DVT, warfarin should be initiated at 5 mg daily and titrated to achieve a target INR of 2.0-3.0, overlapped with initial parenteral anticoagulation for a minimum of 5 days and until the INR is >2.0 for at least 24 hours. 1, 2

Initial Anticoagulation Therapy

Before starting warfarin, patients should receive initial anticoagulation with one of the following:

• Intravenous unfractionated heparin (UFH): 80 U/kg bolus followed by 18 U/kg/hour continuous infusion, adjusted to target aPTT corresponding to anti-factor Xa level of 0.3-0.7 IU/mL 1
• Low molecular weight heparin (LMWH):
  • Enoxaparin: 1 mg/kg twice daily or 1.5 mg/kg once daily 1
  • Dalteparin: 200 IU/kg once daily or 100 IU/kg twice daily 1
  • Tinzaparin: 175 anti-Xa IU/kg once daily 1
• Fondaparinux: Weight-based dosing:
  • <50 kg: 5 mg once daily
  • 50-100 kg: 7.5 mg once daily

  • 100 kg: 10 mg once daily 1

Warfarin Initiation and Monitoring

• Starting dose: 5 mg once daily is recommended for most patients 1, 2, 3
  • Consider lower starting doses (2-4 mg) for elderly patients, those with poor nutritional status, liver disease, or taking medications that affect warfarin metabolism 1, 3
• Overlap period: Continue parenteral anticoagulation for at least 5 days AND until the INR is >2.0 for at least 24 hours 1, 2
• Target INR: 2.0-3.0 1, 2
• Monitoring frequency:
  • Initially: Check INR frequently (every 2-4 days) during the first week 3
  • After stabilization: Gradually extend interval between tests (up to 4-6 weeks maximum) 3

Duration of Therapy Based on Clinical Scenario

• First DVT with reversible risk factor (e.g., surgery, trauma): 3 months 1, 2
• First unprovoked/idiopathic DVT: 6-12 months 1, 2
• Recurrent DVT: Indefinite therapy with periodic reassessment of risk/benefit 1, 2
• Cancer-associated DVT:
  • First-line: LMWH monotherapy for at least 3-6 months or as long as cancer/chemotherapy is ongoing 1
  • If barriers to LMWH exist: Warfarin with target INR 2.0-3.0 is a reasonable alternative 1

Special Considerations

• Avoid loading doses: High initial doses (10 mg) can lead to excessive anticoagulation and increased bleeding risk 3
• Age considerations: Younger patients (<60 years) may require longer duration of parenteral anticoagulation as they tend to achieve therapeutic INR more slowly 4
• Dose adjustments: When adjusting warfarin dose, change the total weekly dose by 5-20% based on INR values 3
• Monitoring for complications: Regular assessment for bleeding is essential 3
• Cancer patients: Have higher risk of recurrent VTE and bleeding; LMWH is preferred over warfarin when possible 1

Common Pitfalls to Avoid

• Excessive initial dosing: Starting with doses >5 mg increases risk of supratherapeutic INR 3
• Inadequate overlap: Stopping parenteral anticoagulation before achieving therapeutic INR increases risk of recurrent thrombosis 1, 2
• Inconsistent monitoring: Failure to monitor INR frequently during initiation phase 3
• Drug interactions: Many medications affect warfarin metabolism; particularly problematic in cancer patients on chemotherapy 1
• Premature discontinuation: Stopping therapy before completing the recommended duration increases recurrence risk 1, 2