Warfarin Dosing and INR Management for DVT Treatment
Initial Warfarin Dosing
Start warfarin at 5 mg once daily for most patients with DVT, with lower starting doses (2-4 mg) reserved for elderly patients, those with poor nutritional status, liver disease, or concurrent medications affecting warfarin metabolism. 1, 2, 3
- The 5 mg starting dose is safe and avoids excessive anticoagulation that can occur with loading doses 4, 5
- Younger patients (<60 years) may require longer time to reach therapeutic INR and should be counseled accordingly 6
- Never use loading doses that rapidly elevate INR, as this creates unnecessary bleeding risk without therapeutic benefit 5
Bridging with Parenteral Anticoagulation
Warfarin must be overlapped with parenteral anticoagulation (LMWH, UFH, or fondaparinux) for a minimum of 5 days AND until INR is ≥2.0 for at least 24 hours. 1, 2, 3, 7
Parenteral Options:
- LMWH (preferred): Enoxaparin 1 mg/kg twice daily or 1.5 mg/kg once daily; Dalteparin 200 IU/kg once daily 1, 2
- UFH: 80 U/kg bolus, then 18 U/kg/hour infusion, adjusted to aPTT ratio 1.5-2.5 (corresponding to anti-Xa 0.3-0.7 IU/mL) 1, 7
- Fondaparinux: Weight-based dosing (<50 kg: 5 mg; 50-100 kg: 7.5 mg; >100 kg: 10 mg once daily) 1, 2
The bridging period is critical because warfarin initially creates a prothrombotic state by depleting protein C before adequately reducing clotting factors II, IX, and X 2, 8
Target INR and Therapeutic Range
The target INR is 2.5, with a therapeutic range of 2.0-3.0 for all DVT patients. 1, 2, 8, 3
- This range is supported by moderate-certainty evidence showing that lower INR targets (1.5-1.9) significantly increase recurrent DVT risk (relative risk 3.25, with 24 additional DVT events per 1000 patients) 8
- Historical INR targets below 2.0 are not validated and should never be used 8
- Higher INR ranges (3.0-4.5) increase bleeding risk without additional benefit for DVT 8
INR Monitoring Schedule
Initial Phase (First 5-7 Days):
- Check INR daily or every other day until therapeutic range is achieved 2
- Start warfarin within 24 hours of initiating parenteral anticoagulation 2, 7
- Continue parenteral therapy until INR ≥2.0 on two consecutive measurements at least 24 hours apart 2
After Achieving Therapeutic INR:
- Weekly INR checks for 2-3 weeks after initial stabilization 2
- Every 2-4 weeks once consistently stable 2
- Can extend to 6-12 weeks in patients with consistently stable INRs 2
After Dose Adjustments:
- Recheck INR within 4 weeks or sooner after any warfarin dose change 2
Special Populations:
- Cancer patients on chemotherapy require more frequent monitoring due to drug interactions affecting warfarin metabolism 2
- Renal impairment (CrCl <30 mL/min): Consider avoiding or dose-adjusting LMWH; UFH may be preferred alternative 1, 2
Duration of Anticoagulation Therapy
Treatment duration depends on the clinical scenario:
- First DVT with reversible/transient risk factor: 3 months 2, 3
- First unprovoked/idiopathic DVT: 6-12 months minimum, consider indefinite therapy 2, 3
- Recurrent DVT: Indefinite therapy with periodic risk/benefit reassessment 2, 3
- Cancer-associated DVT: LMWH monotherapy preferred for at least 3-6 months or as long as cancer is active; if warfarin used, same INR target applies 2, 3
- Thrombophilia (antiphospholipid antibodies, Factor V Leiden, etc.): 6-12 months minimum, consider indefinite therapy 3
Dose Adjustment Strategy
When adjusting warfarin doses, modify the total weekly dose by 5-20% based on INR values:
- Single slightly out-of-range INR does not require dose adjustment 5
- Most dose changes should be small and incremental 5
- Avoid overreacting to isolated INR values 5
Management of Subtherapeutic INR
If INR drops below 2.0 during DVT treatment, immediately restart or continue LMWH bridging until INR returns to therapeutic range for at least 24 hours. 9
- Assess for medication interactions, dietary changes (vitamin K intake), or adherence issues 9
- Failing to bridge with LMWH when INR is subtherapeutic significantly increases recurrent thrombosis risk 9, 8
Critical Pitfalls to Avoid
- Never discontinue parenteral anticoagulation before 5 days AND therapeutic INR achievement 2, 3
- Never use INR targets below 2.0 8
- Never stop anticoagulation prematurely, especially in unprovoked DVT 9
- Never assume therapeutic INR alone means adequate anticoagulation in first 5 days (vitamin K-dependent factors require time to deplete) 2, 8