Warfarin-induced skin necrosis (coumarin necrosis)

Definition

Coumarin necrosis is a rare, severe complication induced by coumarin-type vitamin K antagonists (e.g. warfarin, phenprocoumon): paradoxical clot formation in small skin vessels causes necrosis of the skin and subcutaneous fat. It was first described in 1943.

Occurrence & epidemiology

After taking warfarin, it occurs in about 1 in 10,000 people (reported prevalence 0.01–0.1%). Women are affected more often, usually between 50 and 70 years of age; obesity increases the risk.

Aetiopathogenesis

Vitamin K antagonists lower clotting factors II, VII, IX and X but also the natural clotting regulators protein C and protein S. Protein C has a half-life of about 6 hours, factors II and X of 2–5 days; in the first days after starting the drug this creates a transient prothrombotic state. Predisposing factors are inherited protein C or protein S deficiency, factor V Leiden, antithrombin III deficiency and antiphospholipid antibodies.

Clinical features

• Onset usually between day 2 and day 5 after starting the drug, very rarely after weeks or months.
• First pain and purpura, which turns bluish-black with a red rim within days; then haemorrhagic blisters and full-thickness skin necrosis, sometimes with retiform purpura.
• Predilection for fatty areas: breasts, thighs, buttocks, hips, abdomen.

Histology

Diffuse microthrombi in dermal vessels with endothelial damage and red cell extravasation, without significant inflammation; later full-thickness coagulative necrosis.

Diagnosis

• Clinical diagnosis from timing and distribution.
• Skin biopsy for support and to distinguish it from necrotising fasciitis and calciphylaxis, among others.
• Protein C and protein S blood levels to look for a predisposition.

Differential diagnoses

• Necrotizing fasciitis
• Purpura fulminans
• Antiphospholipid syndrome – skin manifestations (livedo racemosa, Sneddon syndrome)
• Arterial (ischaemic) ulcer
• Erythema ab igne
• Cutaneous angiosarcoma

Keep learning in the app

References (selection)

1. DermNet: Warfarin-induced skin necrosis
2. Warfarin-induced skin necrosis
3. Warfarin induced skin necrosis
4. [The clinical course of coumarin-induced necrosis]

Cross-references