Dear Sir, Skin necrosis is a rare complication of oral anticoagulants. Recently it has been reported in the initial phase of oral anticoagulant treatment, and at the onset of cholestatic vitamin K deficiency, in two patients with congenital deficiency in Pro tein C, a vitamin K-dependent protein (1). We report a similar case who, after 3 complicated attempts of treatment, was success fully anticoagulated by phenprocoumon administered at progres sively increasing doses. A 17 years old male had an ilio-femoral thrombosis confirmed by venography after a minor trauma. Treatment with streptokin ase was followed by intravenous and subcutaneous heparin. On three occasions over eight months, oral anticoagulation was attempted but had to be discontinued. For the first oral anticoagu lation treatment, acenocoumarol (4 mg per day) was adminis tered in conjunction with 11,250 u subcutaneous heparin, twice a day (APTT 72/Control 27). After the second dose, bruises were observed on the lower limbs followed by a hematoma of the calf which appeared a few hours later. Coagulation studies revealed signs of defibrination: FDP: 80 pg/ml (normal: below 40 pg/ml) ; fibrinogen: 0.50 g/1 (normal: 2 to 4 g/1), PT: >50 sec./Control: 12 sec., platelets 165,000/mm3, negative ethanol gelation test and normal euglobulin lysis time. Consequently, acenocoumarol was stopped and subcutaneous heparin continued. Four months later, during a second oral anticoagulant treat ment, after one tablet of acenocoumarol (4 mg) associated with low doses of heparin (5,000 u three times a day) ecchymoses were observed on both legs and disappeared after a few hours. Heparin and acenocoumarol were discontinued for a day and restarted at the same dose of heparin but a lower dose of acenocoumarol (3 mg). Two days later, ecchymotic plaques appeared, followed by bullous reaction, and finally, skin necrosis attributed to an allergic vasculitis to acenocoumarol. Heparin was continued. Two months later, a third oral anticoagulant, fluindione at a dose of 20 mg was given with heparin, but it had to be discontinued after 2 days because of ecchymoses. Since the thrombotic episode had occurred eight months before, it was decided to stop all anticoagulation. Two weeks later, the patient had a recurrent ilio-femoral thrombosis con firmed by venography. Heparin had to be restarted and the patient was referred to our hospital.

In seven patients with acquired von Willebrand's disease (AvWD) associated with lymphoproliferative disorders or benign monoclonal gammopathies, the platelet contents of von Willebrand factor antigen and ristocetin cofactor (vWF:Ag and vWF:RiCof, respectively) were normal. All the multimers of vWF:Ag could be seen in the 1.6% SDS- agarose gel electrophoresis patterns of plasma and platelet lysates. Infusion of 1-deamino-8-D-arginine vasopressin (DDAVP) augmented plasma levels of vWF:Ag and vWF:RiCof of all patients and corrected prolonged bleeding times (BT). However, compared with patients with congenital vWD type I and comparable degrees of baseline abnormalities treated in the same way, vWF:Ag and vWF:RiCof were increased less and cleared more rapidly from plasma and the BT remained normal for a shorter period of time. These studies provide evidence that these AvWD patients have qualitatively normal vWF in plasma, but at lower concentrations, that vWF in platelets is normal both qualitatively and quantitatively, and that cellular vWF can be rapidly released into plasma by DDAVP to correct the hemostatic abnormalities. However, vWF is removed rapidly from plasma, making the correction more transient than in congenital vWD type I.

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