Why Warfarin Must Be Bridged with LMWH in DVT
Warfarin must be bridged with LMWH (or unfractionated heparin) in DVT because warfarin initially creates a paradoxical hypercoagulable state by depleting anticoagulant proteins C and S faster than it depletes procoagulant factors, potentially worsening thrombosis before achieving therapeutic anticoagulation. 1
The Mechanism Behind Bridging
Warfarin works by inhibiting vitamin K-dependent coagulation factors (II, VII, IX, and X), but it also simultaneously depletes proteins C and S, which are natural anticoagulants. 1 The critical problem is timing:
- Proteins C and S have shorter half-lives than the procoagulant factors II, IX, and X 1
- This creates a transient hypercoagulable window during the first 24-72 hours of warfarin therapy 1
- During this period, the patient paradoxically has increased thrombotic risk despite taking an "anticoagulant" 1
- LMWH provides immediate anticoagulation through direct factor Xa inhibition, protecting the patient during this vulnerable period 1
The Evidence-Based Bridging Protocol
Initiate warfarin on the same day as parenteral anticoagulation (LMWH or heparin), not after. 2, 3 This simultaneous start is essential because:
- Warfarin takes 4-5 days to achieve therapeutic effect even when INR appears therapeutic 3
- The INR may reach 2.0 prematurely due to depletion of factor VII (shortest half-life) while factors II, IX, and X remain elevated 1
Continue LMWH for a minimum of 5 days AND until INR ≥2.0 for at least 24 consecutive hours. 2, 3 Both conditions must be met:
- The 5-day minimum ensures adequate depletion of all vitamin K-dependent procoagulant factors 3
- The 24-hour INR requirement confirms stable therapeutic anticoagulation 2, 3
- Never discontinue LMWH early even if INR reaches 2.0 before day 5 3
Why LMWH Is Superior to Unfractionated Heparin for Bridging
LMWH should be used preferentially over unfractionated heparin for the bridging period. 1, 2, 3 The evidence is compelling:
- Reduced mortality compared to unfractionated heparin 1, 3
- Lower major bleeding rates during initial therapy 1, 3
- More predictable pharmacokinetics requiring no monitoring 1, 3, 4
- Unfractionated heparin frequently results in subtherapeutic or supratherapeutic levels, leaving patients unprotected or at bleeding risk 1, 3
- LMWH achieves rapid and consistent therapeutic anticoagulation 1
Critical Pitfalls to Avoid
Never use warfarin alone without heparin bridging in acute DVT. 1, 3 This is particularly dangerous in:
- Heparin-induced thrombocytopenia (HIT) with thrombosis, where warfarin monotherapy can cause venous limb gangrene 1, 3
- Any acute thrombotic event where the hypercoagulable state from warfarin initiation could extend the clot 1
Do not stop LMWH prematurely based on INR alone. 3 The most common error is discontinuing parenteral anticoagulation when INR first reaches 2.0, which typically occurs around day 2-3 due to factor VII depletion alone. 1, 3 This leaves the patient unprotected with inadequate anticoagulation of the other factors.
Check platelet count before and during heparin therapy to rule out HIT. 1, 3 If HIT is suspected clinically (thrombocytopenia, new thrombosis, skin necrosis), immediately:
- Stop all heparin products including LMWH 1, 3
- Switch to a direct thrombin inhibitor (lepirudin or argatroban) 1, 3
- Send HIT antibody testing but do not delay treatment while awaiting results 3
- Do not use warfarin alone in this setting 1, 3
Target INR and Long-Term Management
The target INR is 2.5 (range 2.0-3.0) for all DVT treatment durations. 1, 2 Once therapeutic overlap is achieved: