STUDIES ON ORAL CONTRACEPTIVE-INDUCED CHANGES IN BLOOD-COAGULATION AND FIBRINOLYSIS AND THE ESTROGEN EFFECT ON ENDOTHELIAL-CELLS

Blood coagulation (fibrinogen, thrombin-antithrombin III complexes, TAT, and prothrombin fragment F1+2) and fibrinolytic parameters [fibrin split-product D-dimer, tissue plasminogen activator (t-PA) activity, plasminogen activator inhibitor-1 activity (PAI-1), and plasmin-antiplasmin-complexes (PAP)] were evaluated in 16 women on low estrogen (EE) oral contraceptive (OC) therapy. Blood samples were taken before and between days 18 and 22 of the first, third, and sixth treatment cycle. Fibrinogen levels were found significantly elevated during OC treatment compared with pretreatment values, while TAT and also F1+2 levels remained unchanged. Treatment-induced activation of fibrinolysis was documented by elevated D-dimer [pretreatment (pt): 172 ng/ml (range: 65-640 ng/ml), cycle 6 (c.6): 351 ng/ml (range: 93-960 ng/ml), p < 0.05)] and PAP [(pt: 46.6 ng/ml (13-220 ng/ml), c.6: 66.4 ng/ml (21-200 ng/ml), p < 0.051 plasma levels. Among the fibrinolytic components a decrease in PAI-1 [pt: 10.8 ng/ml (2-56 ng/ml), c.6: 5.3 ng/ml (2.2-14.4 ng/ml), p < 0.05] and an increase in t-PA activity [pt: 0.23 U/ml (0.17-0.45 U/ml), c.6: 0.33 U/ml (0.2-0.9 U/ml), p < 0.05] were detected. Experiments with cultured human endothelial cells (EC) showed that EE influenced neither EC hemostatic regulatory activities (tissue factor, thrombomodulin) nor the secretion of the fibrinolytic components t-PA and PAI-1.