THE ROLE OF THROMBOXANE A(2) IN INCREASED WHOLE-BLOOD PLATELET-AGGREGATION IN ORAL-CONTRACEPTIVE USERS

Epidemiological studies have shown that oral contraceptives increase t he risk of thromboembolic disease in susceptible women however the mec hanisms involved are unclear. We investigated whole blood platelet agg regation in 44 women randomly allocated to 6 cycles of treatment with either gestodene (75ug) or desogestrel (150ug) combined with 30ug ethi nyloestradiol (EE). The in vitro effects of aspirin and a thromboxane synthetase inhibitor, dazmegrel (UK38485) were also investigated. Oral contraceptive treatment caused a significant increase in collagen, ar achidonic acid (AA) and ADP induced whole blood platelet aggregation. PAF induced aggregation was unchanged. There were no significant diffe rences in the levels of platelet aggregation between the desogestrel/3 0ugEE and gestodene/30ugEE groups. In vitro incubation of platelets wi th aspirin and dazmegrel prevented the oral contraceptive induced incr ease in platelet aggregation. Dazmegrel caused an on treatment decreas e in PAF induced aggregation in the desogestrel/30ugEE but not the ges todene/30ugEE group. The results of this study indicate that the use o f oral contraceptives is associated with an increase in platelet aggre gation that is mediated by changes in thromboxane/prostacyclin ratio(T XA(2)/PGI(2)). Although no significant differences were found between the two different progestogen combinations, the effects of dazmegrel o n PAF induced aggregation suggest a possible difference in the progest ogen modifying effects of desogestrel and gestodene which is unmasked when thromboxane synthetase is inhibited.