Calibrated Automated Thrombography (CAT) has been widely used to assess in vitro thrombin generation as an informative intermediary phenotype of coagulation. Interlaboratory exercises have documented a worrisome poor reproducibility. There are some data on the normalisation with an appropriate external reference plasma (RP). This multicentre study of the French-speaking CAT Club aimed at providing further evidence for the usefulness of such a normalisation

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.

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Investigation of 118 patients for protein C deficiency using an immunological and a functional assay, and subsequent investigation of those (nine) found to be deficient, identified 22 patients (14 women, eight men) with protein C deficiency, of whom six were asymptomatic, 15 had histories of venous thromboembolism, and one had a history of arterial thromboembolism. Protein C deficiency was associated in the nine probands with young age at first episode of thromboembolic disease (mean 24-1 (SD 11-9) years), absence of a precipitating condition (five (56%)), and a family history of thromboembolic disease (six (66%)). Investigation of the nine families suggested autosomal dominant transmission of the defect.Thromboembolic episodes were seen in patients with protein C antigen concentrations below 06 U/ml. Mean (SD) protein C antigen concentrations were 0-48 (0-12) U/ml in 18 patients not receiving oral anticoagulant treatment and 0-28 (0-05) U/ml in four receiving such treatment. One patient with severe protein C deficiency (0-16 U/ml) developed skin necrosis soon after starting oral anticoagulant treatment.

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