Inherited deficiency of functional and free form protein S.

We studied hemostatic function in a family with a history of venous thromboembolic disease. In the propositus, a 36-year-old male, the results of assays for the coagulation, anticoagulation and fibrinolytic factors were almost normal. However, the functional protein S activity in his plasma was less than 5% of normal. Similar laboratory findings were noted in his paternal uncle and two sisters who had recurrent thrombotic episodes and in his asymptomatic father as well. The mean total protein S antigen level in these five patients was 37% (range 19-66%) by conventional Laurell rocket immunoelectrophoresis. However, by crossed immunoelectrophoresis of their plasmas and Laurell rocket immunoelectrophoresis of the polyethyleneglycol 6000-treated plasmas, the free form of protein S was undetectable in their plasmas. The levels of C4b-binding protein in the plasma of three of the five patients were in normal range, and that those in the remaining two were below the normal level. These findings suggest that the recurrent thrombotic disease in this family is due to inherited deficiency of protein S, particularly of the functionally active free form of protein S.