EFFECTS OF A THROMBOXANE SYNTHETASE INHIBITOR ON PLATELET-FUNCTION - POSSIBLE RISKS OF USE IN PREGNANCY

It has been proposed that thromboxane synthetase inhibitors may be of use in the treatment of hypertensive disorders of pregnancy. A patient in whom aspirin did not prevent the development of pre-eclampsia in a previous pregnancy was treated with a thromboxane synthetase inhibito r (dazmegrel, Pfizer) in addition to low-dose aspirin. Increased urina ry levels of 6-keto-prostaglandin F1alpha were found throughout pregna ncy, which is consistent with the mode of action. At 17-18 weeks of ge station urinary prostaglandin E2 and F2alpha levels were increased com pared with control pregnancies. These increases in PGE2 and PGF2alpha production were associated with mid-trimester abortion. In vitro studi es were carried out to determine the effects of dazmegrel on platelet eicosanoid production. In whole blood from non-pregnant female volunte ers this compound inhibited thromboxane B2 production and significantl y enhanced prostaglandin E2 production and slightly increased prostacy clin production, demonstrating a redirection of prostaglandin endopero xides. This suggested that similar changes in arachidonic acid metabol ite production may occur in vivo and in vitro, and that thromboxane sy nthetase inhibitors should not be used during early pregnancy, since i ncreased production of prostaglandins E2 and F2alpha may result in pre -term labour or abortion.