A Dutch family with hereditary protein S deficiency.

Protein S, a vitamin K dependent factor, acts as a cofactor for activated protein C in preventing coagulation and stimulating fibrinolysis. Hereditary protein S deficiency has been reported to be an autosomal dominant disorder, associated with an increased risk for developing thrombosis in heterozygotes. Here we present a large Dutch family with familial thrombophilia based on hereditary protein S deficiency. Besides the proband, 27 individuals were tested. Of these, four had had complaints of thromboembolic events. Three of them had protein S levels below the limits of normal, and were considered to be heterozygous for protein S deficiency. Ten others who were also found to be heterozygotes had had no manifestations. Seven of them were under 15 years of age at the time of the investigation. It is uncommon for heterozygotes with protein S deficiency to develop thrombosis before that age, although there have been a few reports. Following these observations, some remarks are made on how to make the laboratory diagnosis of the deficiency, on when to perform family choice of analysis, and on the consequences for therapy.