[Effect of estrogens on cell adhesion molecules in thrombophilic states associated with high blood estrogen levels]

Incidence of thromboembolism in pregnancy is relatively low regarding to many predisposing factors, inclusively the thrombophilia induced changes in coagulation. To evaluate this contradiction we presumed: 1. still not adequately evaluated role of the fibrinolytic system, 2. possible suppression of cytoadhesive molecules in bloodstream and consequently decreased activation of vascular endothelia by high levels of estrogens in the course of pregnancy.

The tests of fibrinolysis (serum levels of fibrinogen, D-dimers, tissue plasminogen activator (tPA) and plasminogen inhibitor 1 (PAI-1) and circulating cytoadhesive molecules (sE-selectin, sP-selectin and ICAM-1) were followed in a group of 66 pregnant women and compared with the unpaired Student's t-test with a group of 16 women after uncomplicated ovarectomy for benign disease. Results were compared with the serum 17 beta-estradiol levels. In pregnancy, significantly decreased levels of both selectins were found: sP-selectin: 159 +/- 39 micrograms/l (SD) vs. 205 +/- 69 micrograms/l (p < 0.05), sE-selectin: 33 +/- 12 micrograms/l (SD) vs. 43 +/- 17 micrograms/l (p < 0.05), meanwhile no significant difference in the concentration of ICAM-1 was found: 248 +/- 80 micrograms/l (SD) vs 285 +/- 101 micrograms/l (SD) (p > 0.05). In concordance, there were found significant negative correlations between serum levels of 17 beta-estradiol and sP selectin (r = -0.35, p < 0.01) and between serum levels of 17 beta-estradiol and sE-selectin (r = -0.21, p < 0.05) but not between 17 beta-estradiol and ICAM-1 (r = -0.1, p > 0.05). There were significant correlations between serum levels of 17 beta-estradiol fibrinogen (r = 0.46, p < 0.01), plasminogen activator I (PAI-1) (r = 0.38) and tissue plasminogen activator I (tPA) (r = 0.22, p < 0.05). No difference was found in serum levels of lipoprotein Lp(a) and naturally occurring inhibitor of the receptor for interleukin 1 (IL-Ira).

This data supports the concept that the decreased serum levels of cytoadhesive molecules of sP-selectin and sE-selectin are dependent on serum estrogen levels and together with a new, estrogen induced, equilibrium of the fibrinolytic system suggest an explanation for the relatively low incidence of thromboembolic events in pregnancy. Decrease of cytoadhesive molecules may be one of explanations of favourable effects of estrogens on the development of atherosclerotic vascular changes.