Warfarin Dosing for Deep Vein Thrombosis
Start warfarin at 5 mg once daily and titrate to achieve a target INR of 2.0-3.0, with mandatory overlap of parenteral anticoagulation (LMWH, UFH, or fondaparinux) for at least 5 days and until the INR is >2.0 for at least 24 hours. 1
Initial Anticoagulation Strategy
Parenteral Anticoagulation Options (Start Immediately)
Before initiating warfarin, you must begin parenteral anticoagulation with one of the following 1:
- Enoxaparin (LMWH): 1 mg/kg subcutaneously twice daily OR 1.5 mg/kg once daily 1
- Dalteparin (LMWH): 200 IU/kg once daily OR 100 IU/kg twice daily 1
- Tinzaparin (LMWH): 175 anti-Xa IU/kg 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
- Fondaparinux: Weight-based dosing (<50 kg: 5 mg; 50-100 kg: 7.5 mg; >100 kg: 10 mg once daily subcutaneously) 1
Warfarin Initiation
Standard starting dose is 5 mg once daily for most patients 1. This approach is safe with minimal risk of anticoagulant overdose 2.
Consider lower starting doses (2-4 mg) in 1, 3:
- Elderly patients (especially those >80 years)
- Poor nutritional status
- Liver disease
- Patients taking medications that potentiate warfarin metabolism
Younger patients (<60 years) may require longer time to achieve therapeutic INR with standard 5 mg dosing and may ultimately need higher maintenance doses 4.
Critical Overlap Period
The parenteral anticoagulant must continue for a minimum of 5 days AND until the INR is >2.0 for at least 24 hours 1. This dual requirement is non-negotiable—both conditions must be met before stopping parenteral therapy.
Common pitfall: Discontinuing LMWH/UFH after 5 days even if INR is subtherapeutic increases risk of recurrent thrombosis 5. The overlap protects against warfarin's initial prothrombotic effect due to rapid depletion of protein C before factors II, IX, and X decline 1.
Target INR and Monitoring
Low-intensity warfarin (INR 1.5-1.9) is inferior to conventional-intensity therapy (INR 2.0-3.0) for preventing recurrent VTE, with 2.8-fold higher recurrence risk and no reduction in bleeding 6.
Monitoring Schedule 3:
- Initial phase: Check INR 2-4 times per week after starting warfarin
- Stabilization phase: Gradually lengthen intervals as INR stabilizes
- Maintenance phase: Maximum interval of 4-6 weeks between tests once stable
Most patients on 5 mg daily starting dose achieve therapeutic INR between 6-10 days 2.
Duration of Anticoagulation Therapy
First DVT with reversible/provoked risk factor: 3 months 1
First unprovoked/idiopathic DVT: 6-12 months 1
Recurrent DVT: Indefinite therapy with periodic risk/benefit 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. Cancer patients have higher risk of both recurrent VTE and bleeding complications 1.
Dose Adjustment Principles
When adjusting warfarin at steady state 3:
- Do not adjust for a single INR slightly out of range
- Most changes should alter the total weekly dose by 5-20%
- Avoid large dose changes that cause INR instability
If INR drops below therapeutic range during treatment: Restart or continue warfarin AND bridge with LMWH until INR returns to 2.0-3.0 for at least 24 hours 5. Failing to bridge with LMWH when INR falls subtherapeutic is a critical error 5.
Management of Elevated INR
For INR ≥9 without bleeding: Give low-dose oral vitamin K1 (2.5 mg phytonadione) 3
For excessive INR with clinically important bleeding: Administer clotting factors (fresh-frozen plasma) plus vitamin K1 3
Special Considerations
Drug interactions: Many medications affect warfarin metabolism, particularly in cancer patients on chemotherapy 1. Reassess INR more frequently when starting/stopping interacting medications.
Medication adherence: Poor adherence is a common cause of subtherapeutic INR 5. Patient education regarding consistent dosing and dietary vitamin K intake is essential 5.
Post-thrombotic syndrome prevention: Consider graduated compression stockings (30-40 mmHg) for 2 years after DVT diagnosis 5.