Abstract
Warfarin-induced skin necrosis is a rare but serious complication of treatment with this commonly prescribed drug. This lesson presents the case of a patient with extensive skin necrosis after inappropriately prolonged warfarinisation and delayed recognition. The condition is briefly reviewed to highlight key features and risk factors.
Lesson
A malnourished 82-year-old woman was referred to the emergency department with an extensive, painful rash. This had worsened despite two weeks treatment for herpes zoster. A month prior to admission she had undergone patellar surgery with a brief interruption of warfarin treatment. Warfarinisation had been commenced a year previously for a postoperative pulmonary embolus. Examination revealed extensive tender and malodorous erythematous plaques with a violacious hue. Central necrotic eschars and vesiculobullous changes were evident and there was involvement of the face, breasts, trunk and limbs (Fig 1).
Multiple tender, malodorous necrotic lesions were found on the patient's trunks, limbs and face. Right panel: these were typically comprised an eschar with surrounding purpura. Approximately 20% of the patient's body surface area was eventually involved.
Warfarin-induced skin necrosis (WISN) was suspected necessitating the cessation of warfarin, and administration of vitamin K and low molecular weight heparin. Broad-spectrum antibiotics, enteral feeding and a three-day course of methylprednisolone, as vasculitis could not be excluded, were commenced. Biopsy of involved skin showed vascular thrombi, patchy necrosis and recent haemorrhage consistent with WISN. No evidence of Warfarin-induced skin necrosis vasculitis was seen. The erythematous plaques progressively became entirely necrotic. Despite prolonged treatment with intravenous antibiotics, the patient died from overwhelming sepsis and multi-organ failure.
Discussion
WISN typically occurs in obese middle-aged women. Lesions have a propensity for areas with increased subcutaneous fat and classically appear on the breast, buttocks, thighs and abdomen.1–4 In the majority, lesions develop 3–6 days after starting warfarin therapy,1,2,4–8 although cases are reported after up to three years.5,7 Affected skin undergoes infarction evolving to necrotic eschar and full thickness skin loss.1–4,8 Clinical history and cutaneous distribution in conjunction with histology helps distinguish WISN from other conditions such as heparin-induced skin necrosis, disseminated intravascular coagulation and necrotising fasciitis.1
Implicated aetiological mechanisms include protein C deficiency, hypersensitivity and a direct toxic effect of warfarin.1,2,8 Histology typically shows diffuse microthrombi within dermal and subcutaneous capillaries, venules and deep veins, with endothelial cell damage resulting in ischaemic skin necrosis and red blood cell extravasation.1 The lack of perivascular inflammation and arteriolar thrombosis, differentiates WISN from the vasculitides.1,3
The mainstay of management is supportive. Treatment is aimed at withdrawing warfarin and reversing its effect on protein C with vitamin K and fresh frozen plasma.1–9 Heparin therapy is utilised to prevent further thrombosis in the postcapillary venules,4 and protein C concentrate is effective although high cost has limited its use. Patients may require local debridement and occasionally skin grafting or even amputation.2 The main causes of death are deep tissue necrosis, sepsis syndrome secondary to wound infection and multi-organ failure.11
Lessons to be elicited
One per cent of the UK population take warfarin.11,12 WISN is a rare but important complication that requires high clinical suspicion and early recognition. Timely initiation of treatment may prevent extensive skin involvement and predisposition to overwhelming bacterial infection. Moreover, this case highlights the importance of determining treatment interval at initiation of anticoagulation and subsequently reviewing the indication for its continuation in all anticoagulated patients encountered in medical practice.
- © 2012 Royal College of Physicians
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