Congenital Protein C Deficiency and Venous Thromboembolism: A Study of Three Dutch Families

Protein C is the zymogen of a vitamin K–dependent serine protease involved in blood coagulation. In the absence of protein C the inactivation of activated factors V and VIIIC is impaired, and the fibrinolytic capacity of the circulating blood is reduced. These conditions promote excessive fibrin formation and thus constitute a risk factor for thrombosis. Using an immunologic assay for protein C, we identified 18 patients (11 male and 7 female) in three unrelated Dutch families as fulfilling the criteria for an isolated protein C deficiency. In 12 patients who were not receiving oral anticoagulant treatment the mean protein C antigen concentration was 0.48±0.09 U per milliliter (±S.D.), and in 6 patients who were receiving adjusted doses of oral anticoagulants and had stable anticoagulation, the mean value was 0.17±0.05 U per milliliter. (The value in healthy subjects is 0.98±0.19 U per milliliter.) Fourteen of the 18 patients had a history of venous thromboembolism, with superficial thrombophlebitis as the hallmark of this condition (in 13 patients). These data are consistent with an autosomal dominant trait with variable expressivity. (N Engl J Med 1983; 309:340–4.) Protein C is the zymogen of a serine protease involved in blood coagulation. 1 2 3 4 It is synthesized in the liver in the presence of sufficient amounts of vitamin K. 1 Protein C can be activated by thrombin, 2 , 3 , 5 and this reaction is greatly accelerated by a protein that is present on the endothelial-cell surface. 6 Activated protein C has been reported to have potent anticoagulant properties, 7 , 8 which are probably related to its inhibitory action on activated factors V and VIIIC and to a stimulatory effect on fibrinolysis. 4 , 5 , 9 , 10 These biochemical findings have led to the hypothesis that a deficiency of protein C will be associated . . .