When should warfarin be introduced in a patient naive to warfarin who develops a Deep Vein Thrombosis (DVT) and is started on heparin?

Warfarin Introduction Timing in DVT Management

Warfarin therapy should be initiated at the same time as heparin therapy for a patient who develops DVT. 1

Initial Anticoagulation Protocol

When managing a patient who is warfarin-naive and has developed a DVT requiring heparin therapy:

1. Start warfarin on day 1 concurrently with heparin therapy 1
2. Continue heparin overlap with warfarin until:
   • INR reaches therapeutic range (2.0-3.0) 1
   • Therapeutic INR has been maintained for at least 2 days 1
   • Total minimum heparin duration of 5 days 1

Rationale for Concurrent Initiation

The concurrent initiation approach is recommended because:

• Warfarin has a delayed onset of action (takes 36-72 hours to achieve significant anticoagulant effect)
• Heparin provides immediate anticoagulation while warfarin takes effect
• Early warfarin initiation allows for dose titration and achievement of stable therapeutic levels

Important Considerations and Precautions

Protein C and S Depletion

• Caution: Warfarin initially depletes proteins C and S (natural anticoagulants) before affecting other vitamin K-dependent clotting factors 1
• This can create a transient hypercoagulable state if warfarin is given without heparin coverage 2
• The heparin overlap prevents this paradoxical prothrombotic effect

Initial Dosing

• Typical starting dose: 5 mg once daily 1
• Adjust based on:
  • Age (lower doses for elderly)
  • Nutritional status
  • Concurrent medications affecting metabolism
  • Liver function 1

Monitoring Requirements

• Check INR daily after initial dose until stabilized in therapeutic range 3
• Target INR: 2.5 (range 2.0-3.0) 1
• Once stable, monitoring frequency can be reduced to intervals based on stability (typically weekly initially, then less frequently) 1

Duration of Anticoagulation Therapy

After initiating warfarin, the total duration of therapy depends on the etiology of the DVT:

• Known reversible risk factor: 3+ months 1
• First idiopathic event: 6+ months 1
• Recurrent idiopathic VTE or continuing risk factors: 12+ months or indefinite 1
• Thrombophilic conditions: Duration varies based on specific condition 1

Potential Pitfalls to Avoid

1. Never start warfarin without heparin coverage in acute DVT due to risk of warfarin-induced skin necrosis and venous limb gangrene 2

2. Do not discontinue heparin prematurely before achieving therapeutic INR for at least 2 days, even if INR rises quickly 1

3. Avoid high loading doses (>5 mg) in elderly patients, those with poor nutrition, or hepatic dysfunction 1

4. Do not delay warfarin initiation - starting on day 1 with heparin is optimal for most patients 1

By following these evidence-based recommendations, you can optimize the management of DVT in warfarin-naive patients while minimizing both thrombotic and bleeding complications.