What is the appropriate action for a patient developing severe pain in the right leg with areas of skin necrosis one week after starting Coumadin (warfarin) therapy?

Management of Warfarin-Induced Skin Necrosis

The appropriate action for a patient who develops severe pain in the right leg with areas of skin necrosis one week after starting Coumadin therapy is to stop Coumadin and start heparin therapy immediately. 1, 2

Pathophysiology and Recognition

Warfarin-induced skin necrosis is a rare but serious complication occurring in approximately 0.01% to 0.1% of patients initiating warfarin therapy 1. The condition typically presents:

• Between days 3-8 of warfarin therapy
• With painful, erythematous lesions that progress to hemorrhagic bullae and full-thickness necrosis
• In areas with substantial subcutaneous fat (breasts, thighs, buttocks)
• More commonly in middle-aged women

The pathophysiology involves warfarin's inhibition of both procoagulant factors (II, VII, IX, X) and anticoagulant proteins (Protein C and S). Because Protein C has a shorter half-life (4-6 hours) compared to the procoagulant factors (24-72 hours), a temporary hypercoagulable state occurs during warfarin initiation 1.

Management Algorithm

1. Immediate discontinuation of warfarin - This is the critical first step to prevent further progression of necrosis 1, 2

2. Initiate heparin therapy - Switch to unfractionated heparin or low molecular weight heparin for anticoagulation 1, 2

   • Heparin provides immediate anticoagulation through a different mechanism that doesn't affect Protein C levels

3. Administer vitamin K - To reverse warfarin's effects 1, 3

   • For serious cases: 5-10 mg intravenously by slow infusion

4. Consider fresh frozen plasma - In severe cases to replenish coagulation factors 3

5. Surgical evaluation - For potential debridement of necrotic tissue 1, 2

6. Long-term anticoagulation planning - Options include:

   • Direct oral anticoagulants (rivaroxaban, apixaban) 1, 4
   • Continued heparin therapy 1
   • Cautious reintroduction of warfarin (if necessary) with very low doses and concurrent heparin coverage 1

Risk Factors and Prevention

The FDA label and clinical guidelines identify several risk factors for warfarin-induced skin necrosis 1, 2:

• Protein C deficiency
• Protein S deficiency
• High loading doses of warfarin
• Female gender
• Middle age

Important Considerations

• Do not delay treatment - Skin necrosis can progress rapidly and lead to permanent tissue damage, amputation, or death 2
• Avoid restarting warfarin - Direct oral anticoagulants are preferred for long-term management 4
• Bridging with heparin is not always protective - Cases have been reported despite appropriate heparin bridging 5, 6
• Surgical consultation - May be necessary for wound care, debridement, or skin grafting in severe cases 2

Prognosis

With prompt recognition and appropriate management, progression of necrosis can be halted. However, established necrotic areas may require surgical intervention, and in severe cases, amputation may be necessary 2, 4.