Pharmacology · Year 2 · from Pharmacology
Case 1: Warfarin-Induced Skin Necrosis (Protein C Deficiency)
Clinical Scenario
A 52-year-old female develops painful skin lesions 4 days after starting warfarin therapy for newly diagnosed deep vein thrombosis.
Patient Demographics
- Age: 52 years
- Sex: Female
- Weight: 85 kg
Chief Complaint
Painful, darkening skin patches on thighs and breasts for 24 hours
History of Present Illness
The patient was diagnosed with left lower extremity deep vein thrombosis 5 days ago and started on warfarin 10 mg daily without heparin bridging. She developed painful, erythematous patches on her bilateral thighs and left breast that have rapidly progressed to purple-black discoloration with blistering.
Physical Examination
- Vital Signs: BP 138/82 mmHg, HR 92 bpm, RR 16, T 37.4C
- General: Anxious, in moderate pain
- Skin:
- Bilateral thighs: 8-10 cm areas of violaceous discoloration with central necrosis and surrounding erythema
- Left breast: 5 cm area of purple-black eschar with bullae
- Areas are exquisitely tender to palpation
- Extremities: Left lower extremity swelling consistent with DVT
Workup and Results
| Test | Result | Reference Range |
|---|---|---|
| INR | 3.8 | 2.0-3.0 (therapeutic) |
| Protein C activity | 28% | 70-140% |
| Protein S activity | 85% | 60-150% |
| D-dimer | 4.2 mcg/mL | <0.5 mcg/mL |
| Platelet count | 245,000/mcL | 150,000-400,000/mcL |
Skin biopsy: Thrombosis of dermal vessels with overlying epidermal necrosis
Diagnosis
Warfarin-induced skin necrosis due to acquired protein C deficiency in a patient with underlying heterozygous protein C deficiency
Pharmacodynamic Principles Illustrated
- Differential protein half-lives: Protein C (vitamin K-dependent anticoagulant) has a shorter half-life (8 hours) than clotting factors II and X (60-72 hours).
- Transient hypercoagulable state: Early warfarin therapy depletes protein C before adequate anticoagulation is achieved, creating paradoxical thrombosis.
- Therapeutic index: This adverse effect demonstrates that even drugs within therapeutic range can cause severe harm.
- Receptor/pathway effects: Warfarin affects the vitamin K cycle broadly, impacting both procoagulant and anticoagulant proteins.
Treatment
- Immediately discontinue warfarin
- Administer vitamin K 10 mg IV to reverse warfarin effect
- Start therapeutic anticoagulation with heparin or LMWH
- Fresh frozen plasma or protein C concentrate for severe cases
- Wound care with possible surgical debridement of necrotic tissue
- Consider alternative anticoagulation (DOAC) for long-term therapy
- Genetic testing for hereditary protein C deficiency
Clinical Image
Warfarin-induced skin necrosis showing characteristic violaceous discoloration with central necrosis. This occurs in areas with significant subcutaneous fat (breast, thighs, buttocks) due to microvascular thrombosis.
Image Source: Wikimedia Commons License: CC BY-SA 3.0 URL: https://commons.wikimedia.org/wiki/File:Warfarin_necrosis.jpg