Association of Protein S Deficiency with Thrombosis in a Kindred with Increased Levels of Plasminogen Activator Inhibitor-1

15 October 1993 | Volume 119 Issue 8 | Pages 779-785

Objective: A single kindred in North America with venous thrombosis was described as having defective fibrinolysis because of increased levels of plasminogen activator inhibitor-1 (PAI-1). Our study describes the discovery of protein S deficiency in this kindred and its association with venous thromboembolism.

Design: A family study.

Setting: Community.

Participants: Twenty-eight adults (ages 21 to 71 years) from three generations of the kindred; seven had a history of venous thromboembolism.

Measurements: Plasma levels of total and free protein S antigen, as well as the activities of protein S, protein C, PAI-1, and antithrombin III.

Results: Six of 7 persons (86%) with a history of venous thromboembolism were deficient in total and free protein S; of 21 asymptomatic members, 9 were deficient in protein S (P = 0.08). When compared with these 9 asymptomatic family members, the 6 persons with protein 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 thrombosis (95% CI, –9.9 to 7.0).

Conclusions: In this kindred, a deficiency 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 familial thrombosis. The utility of the routine measurement of PAI-1 activity in the evaluation of familial thrombosis has not been established.

Author and Article Information

From the Walter Reed Army Institute of Research and the Walter Reed Army Medical Center, Washington, D.C.
Requests for Reprints: Charles D. Bolan, MD, Department of Hematology Oncology, Ward 78, Walter Reed Army Medical Center, Washington, DC 20307.
Acknowledgments: The authors thank Dr. Jose-Antonio Fernandez for measuring the plasma ß chain-C4BP concentration in the laboratory of Dr. John H. Griffin at the Scripps Research Institute in La Jolla, California.