The question concerns an 82-year-old woman who has been treated with warfarin since December 1994.

Fråga: The question concerns an 82-year-old woman who has been treated with warfarin since December 1994. She now has developed painful necrotic skin lesions on her left inner thigh with a diameter of 5 cm. According to the clinical picture, the skin necrosis is likely to be caused by warfarin, although the results of the skin biopsy taken are inconclusive. The physician would like some more documentation about this possible side effect, especially with regard to treatment.

Sammanfattning: Skin necrosis is a rare, but well-known side effect of oral anticoagulants such as warfarin. There is no specific therapy, but discontinuation of warfarin is usually recommended. The skin lesins may heal spontaneously or after surgical intervention.

Svar: The question concerning skin necrosis following therapy with oral anticoagulants has been dealt with in a number of earlier Drugline questions. In short, all oral anticoagulants have been described to cause skin necrosis and up to about 200 cases have been reported in the literature. A description of the skin lesions is given in (1). The incidence with warfarin treatment is about 0.1 per cent. An elderly adipose woman suffering from a malignant disease seems to be at a higher risk to develop this side effect and the possibility of concurrent malignancy should be taken into consideration. The skin lesions usually appear within 3-10 days after the treatment is started, but may also appear much later or even after several courses of anticoagulant treatment (2). The pathophysiology seems uncertain. Direct toxicity on the small arteriolar vessels, allergic reactions and factor VII deficiency have been suggested (2), as well a a deficiency in protein C or its co-factor protein S (3). Protein C undergoes carboxylation in the liver before it serves as an anticoagulant, a step which is prevented by warfarin. A low protein C activity relative to the vitamin K dependent clotting factors during the first few days of warfarin therapy is suggested to lead to small vessel thrombosis, predominant of the vessels of the skin overlying fatty areas of the body. Therefore, starting warfarin with a low inital dose which is gradually increased, may be preventive (3). There is no specific therapy. After appearance of the necrotic lesions, warfarin treatment is usually discontinued. The skin lesions may heal spontaneously or after surgical intervention. 1 Drugline nr 07219 (year 1989) (enclosed) 2 Sjöberg A, Mellblom L, Konrad P, Holmberg B, Bergquist D: Sex fall av warfarinframkallad hudnekros. Läkartidningen 1986; 83: 4089-4092 3 Locht H, Lindström FD: Severe skin necrosis following warfarin therapy in a patient with protein C deficiency. J Intern Med 1993; 233: 287-289