Association of protein S deficiency with thrombosis in a kindred with increased levels of plasminogen activator inhibitor-1.
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.


METHODS
A family study.


METHODS
Community.


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


METHODS
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.
Bolan
C D
CD
Department of Hematology Oncology, Walter Reed Army Medical Center, Washington, DC 20307.
Krishnamurti
C
C
Tang
D B
DB
Carrington
L R
LR
Alving
B M
BM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000990:Antithrombin III / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011486:Protein C / Q000378:metabolism; D018455:Protein S Deficiency; D012016:Reference Values; D013924:Thrombophlebitis / Q000097:blood* / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; D014280:Triglycerides; D000990:Antithrombin III