The long-term goal of this study is to gain insight into the mechanisms involved in the development of thrombosis in men with coronary heart disease and other individuals who are at statistical risk. A possible cause of thrombosis is a state of """"""""hypercoagulability"""""""", for example, abnormally high titers of clotting factors in plasma. In women using oral contraceptives containing estrogenic compounds, as well as pregnant women, the plasma titer of Hageman factor (HF, factor XII) is doubly elevated. The cold-induced increase in factor VII and plasma renin activities observed in women using oral contraceptives reflect their high HF titers. Recently, the Framingham Heart Study reported that men with coronary heart disease have hyperestrogenemia. Since estrogens increase prolactin secretion, both estrogen and prolactin may play a role in raising HF titer, possibly by affecting protein synthesis. This project will study the mechanisms involved in HF activation, synthesis and catabolism, as well as the hormonal control of its titer in plasma. The specific objectives are: 1) to determine whether men with coronary heart disease have high HF titers, and whether their plasmas manifest enhanced cold-activation of factor VII and prorenin, HF coagulant and antigen titers, plasma renin and factor VII activities will be measured in fresh and cold-stored plasmas and will be related to their estradiol and prolactin titers; 2) to determine whether the high HF titer observed in estradiol, prolactin and dexamethasone-treated rats is due to de novo synthesis or decreased degradation of HF, liver perfusion techniques and in vivo catabolism studies will be performed; 3) to determine whether the inhibition of prolactin secretion will reduce HF titer, HF titer will be measured in bromocriptine-treated rats; 4) to determine whether the thromboembolic and hypertensive complications of pregnancy are related to high HF titer, a longitudinal study of women throughout their pregnancy will be performed using methods in the study of men with coronary heart disease; 5) to determine whether corticosteroid therapy raises HF titer in humans, HF coagulant and antigen titers will be measured in patients receiving decadron or prednisone; 6) to determine whether an activated HF-C1 esterase inhibitor complex is formed in women using oral contraceptives and in sickle cell patients during vaso-occlusive crises, crossed immunoelectrophoretic techniques will be used. Statistical methods of analyses will include the Student's t test, Pearson's coefficient of correlation and multiple correlation.
