Effects of low and high dose oral contraceptives on blood coagulation and thrombogenesis induced by vascular subendothelium exposed to flowing human blood.
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 micrograms ethinyl estradiol and 150 micrograms desogestrel per day) and [3] high estrogen content (50 micrograms ethinyl estradiol and 125 micrograms 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 less than 0.001) and fibrinogen (2.3 +/- 0.1 and 2.6 +/- 0.1 vs. 2.0 +/- 0.1 g/l, P less than 0.05); and decreased antithrombin III activity (95 +/- 3 and 92 +/- 3 vs. 101 +/- 3 %, P less than 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 less than 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.
Inauen
W
W
Department of Internal Medicine, University Hospital, Inselspital, Bern, Switzerland.
Stocker
G
G
Haeberli
A
A
Straub
P W
PW
D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001772:Blood Cell Count / Q000187:drug effects; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects*; D003277:Contraceptives, Oral, Combined / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D017135:Desogestrel; D004305:Dose-Response Relationship, Drug; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D005260:Female; D005337:Fibrin / Q000096:biosynthesis / Q000187:drug effects; D005340:Fibrinogen / Q000187:drug effects; D006400:Hematocrit; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D009652:Norpregnenes / Q000009:adverse effects / Q000494:pharmacology*; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D011817:Rabbits; D013918:Thrombin Time
D003277:Contraceptives, Oral, Combined; D006454:Hemoglobins; D009652:Norpregnenes; D004997:Ethinyl Estradiol; D017135:Desogestrel; D000990:Antithrombin III; D005337:Fibrin; D005340:Fibrinogen; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D001663:Bilirubin