ASSOCIATION OF PROTEIN-S DEFICIENCY WITH THROMBOSIS IN A KINDRED WITHINCREASED LEVELS OF PLASMINOGEN-ACTIVATOR INHIBITOR-1

Objective: A single kindred in North America with venous thrombosis wa s described as having defective fibrinolysis because of increased leve ls of plasminogen activator inhibitor-1 (PAI-1). Our study describes t he discovery of protein S deficiency in this kindred and its associati on with venous thromboembolism. Design: A family study. Setting: Commu nity. Participants: Twenty-eight adults (ages 21 to 71 years) from thr ee generations of the kindred; seven had a history of venous thromboem bolism. Measurements: Plasma levels of total and free protein S antige n, as well as the activities of protein S, protein C, PAI-1, and antit hrombin III. Results: Six of 7 persons (86%) with a history of venous thromboembolism were deficient in total and free protein S; of 21 asym ptomatic members, 9 were deficient in protein S (P = 0.08). When compa red with these 9 asymptomatic family members, the 6 persons with prote in S deficiency and a history of thrombosis tended to smoke (P = 0.01) and to have higher triglyceride levels (P = 0.001). Overall, the mean PAI-1 activity in the 7 persons who had thrombosis was 7.9 kAU/L (AU/ mL) and was 9.3 kAU/L (AU/mL) in the 21 persons who did not have throm bosis (95% CI, -9.9 to 7.0). Conclusions: In this kindred, a deficienc y of total and free or functional protein S is the cause of thrombosis . Measurement of PAI-1 activity was not useful in the evaluation of fa milial thrombosis. The utility of the routine measurement of PAI-1 act ivity in the evaluation of familial thrombosis has not been establishe d.