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 < 0.05] 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.
PIP: In Vienna, Austria, health workers took blood samples from 16 healthy, nonsmoking 19-35 year old women before and after they began using a combined oral contraceptive (OC) (Gynovin) (30 mcg ethinyl estradiol and 75 mcg gestodene) to assess the OC's effects on blood coagulation and fibrinolysis and the effect of the estrogen component on endothelial cells. Fibrinogen levels increased significantly after OC use (283 mg/dl vs. 342 mg/dl after the 1st treatment cycle; p .005). These levels remained significantly higher (326 mg/dl and 339 mg/dl after the 2nd and 3rd treatment cycles; p .005 and .05, respectively). Thrombin antithrombin III complex (TAT) and prothrombin fragment F1+2 levels increased just minimally during OC treatment. Levels of fibrin split-product D-dimer, plasma tissue plasminogen activator (t-PA) activity, and plasmin-antiplasmin (PAP) complexes were significantly higher during all OC treatment cycles than they were before treatment. Active plasminogen activator inhibitor (PAI-1) antigen, t-PA, and urokinase plasminogen activator antigen levels fell significantly after OC treatment and remained low during OC treatment. Experiments with the culture of human umbilical vein endothelial cells showed that ethinyl estradiol did not significantly affect the tissue factor content or surface thrombomodulin activity of these endothelial cells (i.e., hemostatic regulatory activities). It also did not change the secretion of the fibrinolytic components t-PA and PAI-1. None of the women developed thrombosis. Even though these findings did not clearly show OC-induced hemostatic activation in this relatively small group of women, clinical researchers should still determine activation markers to monitor the activation state of blood coagulation in certain OC users, such as obese women and those who smoke cigarettes.