Warfarin Dosing for Deep Vein Thrombosis (DVT)
For treating DVT, initiate warfarin at 5 mg daily (or 2-4 mg in elderly patients), overlap with parenteral anticoagulation (UFH, LMWH, or fondaparinux) for a minimum of 5 days, and continue overlap until INR is ≥2.0 for at least 24 hours, targeting a therapeutic INR range of 2.0-3.0. 1
Initial Anticoagulation Strategy
Parenteral Anticoagulation Options (Start Immediately)
You must initiate parenteral anticoagulation before or simultaneously with warfarin to prevent the paradoxical hypercoagulable state that occurs in the first 24-48 hours of warfarin therapy due to rapid depletion of protein C. 1
Choose one of the following:
- Enoxaparin (LMWH): 1 mg/kg subcutaneously twice daily OR 1.5 mg/kg once daily 1
- Dalteparin (LMWH): 200 IU/kg subcutaneously once daily OR 100 IU/kg twice daily 1
- Tinzaparin (LMWH): 175 anti-Xa IU/kg subcutaneously 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
- Unfractionated heparin (UFH): 80 U/kg IV 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
Warfarin Initiation Dosing
Standard starting dose: 5 mg once daily for most patients. 1, 2
Reduced starting dose: 2-4 mg once daily for patients who are: 1, 2
- Elderly (>70-75 years old)
- Poor nutritional status
- Liver disease
- Taking medications that potentiate warfarin metabolism
Important caveat: While older guidelines suggested a 10 mg loading dose for the first 2 days in healthy outpatients 3, the current American Heart Association recommendation favors 5 mg daily as the standard approach, which has been shown to be safe with low risk of overdose. 1, 4 The 5 mg approach avoids excessive INR elevation and is more practical for outpatient management. 4, 2
Overlap Period and INR Monitoring
Continue parenteral anticoagulation for at least 5 days AND until INR ≥2.0 for at least 24 hours. 1 Both conditions must be met before stopping parenteral therapy. 1
INR Monitoring Schedule
- Days 1-3: No INR needed (warfarin effect minimal) 4
- Day 4: First INR check 4
- Day 6: Second INR check 4
- Subsequently: Every 2-4 days until stable, then gradually extend to every 4-6 weeks once therapeutic and stable 2
Common pitfall: Stopping parenteral anticoagulation too early (before day 5 or before INR therapeutic for 24 hours) increases risk of recurrent thrombosis due to incomplete suppression of vitamin K-dependent clotting factors. 1
Target INR and Dose Adjustments
Target INR: 2.0-3.0 for DVT treatment. 1, 5
Do not use low-intensity warfarin (INR 1.5-1.9) for DVT treatment, as it results in 2.8-fold higher recurrence rate without reducing bleeding risk. 5
Dose Adjustment Principles
- Single INR slightly out of range: No dose change needed 2
- Sustained out-of-range INR: Adjust total weekly dose by 5-20% 2
- INR >9 without bleeding: Give vitamin K1 2.5 mg orally 2
- INR elevated with clinically important bleeding: Give fresh-frozen plasma plus vitamin K1 2
Expected timeline: Most patients achieve therapeutic INR by day 6, though younger patients (<60 years) may require 10-11 days. 4, 6 The mean final maintenance dose is typically 5-6 mg daily. 7
Duration of Therapy Based on Clinical Scenario
First DVT with reversible/provoked risk factor: 3 months 1
First unprovoked/idiopathic DVT: 6-12 months, then reassess risk/benefit for extended therapy 1
Recurrent DVT: Indefinite therapy with periodic reassessment 1
Cancer-associated DVT: LMWH monotherapy is preferred over warfarin for at least 3-6 months or as long as cancer/chemotherapy is ongoing. 1 If warfarin must be used, same INR target of 2.0-3.0 applies, but expect more difficulty maintaining therapeutic range due to drug-drug interactions and nutritional changes. 1
Special Populations
Renal Impairment
- CrCl <30 mL/min: UFH is preferred as it's hepatically metabolized; if using warfarin, start with 2-4 mg daily and monitor more frequently 8, 2
Obesity
- Warfarin dosing is not weight-based; use standard 5 mg starting dose 1
- Parenteral anticoagulation should be weight-based as noted above 1