The role of thromboxane A2 in increased whole blood platelet aggregation in oral contraceptive users
Norris, L.A.; Devitt, M.; Bonnar, J.
Thrombosis Research 81(4): 407-417
1996
ISSN/ISBN: 0049-3848 PMID: 8907290 DOI: 10.1016/0049-3848(96)00013-8Document Number: 305228
In Ireland, researchers randomly assigned 44 healthy women, 18-34 years old, to either the group using the oral contraceptive (OC) containing 30 mcg ethinyl estradiol (EE) and 150 mcg desogestrel (Marviol) or the group using the OC containing 30 mcg EE and 75 mcg gestodene (Femodene) to determine the progestogen's modifying effect on whole blood platelet aggregation. In vitro, they incubated the platelets with aspirin and a thromboxane synthetase inhibitor (dazmegrel) to examine the role of thromboxane (TXA2) in any increased aggregation. The women were recruited from the postnatal clinic of the Coombe Women's Hospital in Dublin. OC use caused a significant increase in collagen-, arachidonic acid- (AA), and ADP-induced whole blood platelet aggregation (p 0.03, 0.001, and 0.01, respectively). It had no effect on PAF-induced aggregation, however. No significant differences in platelet aggregation levels existed between gestodene and desogestrel. Both aspirin and dazmegrel had a significant inhibitory effect on OC-induced increase in platelet aggregation in terms of collagen, AA, and ADP. This suggests that OCs act synergistically with ADP to cause a TXA2 mediated increase in platelet aggregation. Dazmegrel, but not aspirin, caused a decrease in PAF-induced platelet aggregation in the desogestrel/30 mcg EE group only, suggesting a possible difference in the modifying effects of the 2 progestogens, which is revealed when thromboxane synthetase is inhibited. Dazmegrel's inhibitory effect suggests that increased thromboxane synthetase activity plays a role in the OC-induced platelet hyperactivity. Changes in the TXA2/prostacyclin ratio appear to mediate OCs' effect on platelet aggregation.