Effects of low and high dose oral contraceptives on blood coagulation and thrombogenesis induced by vascular subendothelium exposed to flowing human blood

Abstract

We investigated the effect of oral contraceptives with low and high estrogen concentration on blood coagulation and thrombogenesis, induced by vascular subendothelium of rabbit aorta exposed to flowing human blood. Twenty healthy women intending to take oral contraceptives were studied [1]before drug ingestion (control), and subsequently during the intake of oral contraceptives with [2]low estrogen content (20 μg ethinyl estradiol and 150 μg desogestrel per day) and [3] high estrogen content (50 μg ethinyl estradiol and 125 μg desogestrel per day). All experiments were performed between day 17 and 21 of the menstrual cycle and drug effects were studied during the third tablet cycle. Deposition of fibrin, platelets and platelet thrombi on vascular subendothelium was tested at a defined blood flow and wall shear rate (10 ml/min, 650 s .1) and was quantified by morphometrical techniques. Treatment with the low and high dose contraceptive increased the plasma levels of ethinyl estradiol (728 ± 139 and 1438 ± 212 vs. 0 fmol/ l [low and high dose vs. control], means ± SEM, P<0.001) and fibrinogen (2.3 ± 0.1 and 2.6 ± 0.1 vs. 2.0 ± 0.1 g/l, P<0.05); and decreased antithrombin III activity (95 ±3 and 92 ± 3 vs. 101 ± 3 %, P<0.05). Fibrin deposition on vascular subendothelium was enhanced by the high dose contraceptive only (47 ± 4 vs. 35 ±4 % coverage of the subendothelial surface with fibrin, high dose vs. control, P<0.05). The subendothelial deposition of platelets and platelet thrombi was not changed by contraceptive treatment. These results indicate that treatment with high dose contraceptives leads to an increase of fibrin-subendothelial interactions, whereas low dose contraceptives do not significantly alter the blood-subendothelium interactions observed in this ex vivo model of thrombogenesis.