The role of thromboxane A2 in increased whole blood platelet aggregation in oral contraceptive users.
Thromb Res
; 81(4): 407-17, 1996 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-8907290
ABSTRACT
Epidemiological studies have shown that oral contraceptives increase the risk of thromboembolic disease in susceptible women however the mechanisms involved are unclear. We investigated whole blood platelet aggregation in 44 women randomly allocated to 6 cycles of treatment with either gestodene (75ug) or desogestrel (150ug) combined with 30ug ethinyloestradiol (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, arachidonic acid (AA) and ADP induced whole blood platelet aggregation. PAF induced aggregation was unchanged. There were no significant differences in the levels of platelet aggregation between the desogestrel/30ugEE and gestodene/30ugEE groups. In vitro incubation of platelets with aspirin and dazmegrel prevented the oral contraceptive induced increase in platelet aggregation. Dazmegrel caused an on treatment decrease in PAF induced aggregation in the desogestrel/30ugEE but not the gestodene/30ugEE group. The results of this study indicate that the use of oral contraceptives is associated with an increase in platelet aggregation that is mediated by changes in thromboxane/prostacyclin ratio(TXA2/PGI2). Although no significant differences were found between the two different progestogen combinations, the effects of dazmegrel on PAF induced aggregation suggest a possible difference in the progestogen modifying effects of desogestrel and gestodene which is unmasked when thromboxane synthetase is inhibited.
ABSTRACT
PIP 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.
Palavras-chave
Biology; Clinical Research; Clinical Trials; Contraception; Contraceptive Agents; Contraceptive Agents, Female; Contraceptive Agents, Progestin; Contraceptive Methods; Desogestrel; Developed Countries; Diseases; Embolism; Enzyme Inhibitors; Enzymes And Enzyme Inhibitors; Europe; Family Planning; Gestodene; Hematological Effects; Hemic System; In Vitro; Ireland; Northern Europe; Oral Contraceptives; Oral Contraceptives, Combined; Physiology; Platelet Aggregation; Research Methodology; Research Report; Thromboembolism; Vascular Diseases
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Base de dados:
MEDLINE
Assunto principal:
Tromboxano A2
/
Plaquetas
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Agregação Plaquetária
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Anticoncepcionais Orais Combinados
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Anticoncepcionais Orais Hormonais
Tipo de estudo:
Clinical_trials
Limite:
Adolescent
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Adult
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Female
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Humans
Idioma:
En
Ano de publicação:
1996
Tipo de documento:
Article