Effect of Low-Dose Aspirin on Fetal and Maternal Generation of Thromboxane by Platelets in Women at Risk for Ppregnancy-Induced Hypertension

Abstract

There is evidence that aspirin in low doses favorably influences the course of pregnancy-induced hypertension, but the mechanism, although assumed to involve suppression of the production of thromboxane by platelets, has not been established. We performed a randomized study of the effect of the long-term daily administration of 60 mg of aspirin (n = 17) or placebo (n = 16) on platelet thromboxane A2 and vascular prostacyclin in women at risk for pregnancy-induced hypertension. Low doses of aspirin were associated with a longer pregnancy and increased weight of newborns. Serum levels of thromboxane B2, a stable product of thromboxane A2, were almost completely (greater than 90 percent) inhibited by low doses of aspirin. The urinary excretion of immunoreactive thromboxane B2 was significantly reduced without changes in the level of 6-keto-prostaglandin F1 alpha, a product of prostacyclin. Mass spectrometric analysis showed that aspirin reduced the excretion of the 2,3-dinor-thromboxane B2 metabolite--mainly of platelet origin--by 81 percent and of thromboxane B2, probably chiefly of renal origin, by 59 percent. The urinary excretion of 6-keto-prostaglandin F1 alpha and of its metabolite 2,3-dinor-6-keto-prostaglandin F1 alpha was not affected. Low doses of aspirin only partially (63 percent) reduced neonatal serum thromboxane B2. No hemorrhagic complications were observed in the newborns. Thus, in women at risk for pregnancy-induced hypertension, low doses of aspirin selectively suppressed maternal platelet thromboxane B2 while sparing vascular prostacyclin, but only partially suppressed neonatal platelet thromboxane B2, allowing hemostatic competence in the fetus and newborn.

Endogenous biosynthesis of arachidonic acid epoxides in humans: increased formation in pregnancy-induced hypertension.

“…This condition correlates with their mean arterial pressure, plasma lactate dehydrogenase, and the degree of thrombocytopenia (39). Several small studies, which suggest that pretreatment with aspirin may reduce the incidence of PIH in women at risk of developing the disease (40)(41)(42)(43), also support the possibility that thromboxane formation is of functional importance, perhaps contributing to reduced placental blood flow (22,24).…”

Platelet function in pregnant women receiving aspirin and dipyridamole

“…In diseased states coagulability is further increased, including placental coagulation leading to uteroplacental insufficiency. There are several reports showing the efficacy of antiplatelet therapy among selected women deemed to be at high risk for preeclampsia, IUGR, and intrauterine fetal death [1][2][3][4]. Other indications for antiplatelet therapy include recurrent spontaneous abortion and the detection of autoimmune antibodies [5].…”

“…Antiplatelet therapy with low-dose aspirin, with or without dipyridamole, has been reported to be effective in the prevention of preeclampsia, intrauterine growth retardation (IUGR), and pregnancy losses, and its prophylactic use in patients at high risk has become increasingly popular [1][2][3][4][5]. Daily oral intake of aspirin and dipyridamole is usually started before pregnancy or in the first trimester and continued up to 30-37 weeks of gestation.…”

État des connaissances : prise en charge thérapeutique de la prééclampsie

“…L'effet bénéfique de l'association aspirine-dipyridamole chez les femmes enceintes à haut risque de prééclampsie lance le débat international. Les années qui suivent, voient défiler une succession d'articles en faveur de l'efficacité de l'aspirine [64][65][66][67]. Ensuite, vint l'essai EPREDA [68] qui tend à montrer que l'efficacité suggérée est d'autant plus réelle que la patiente pré-sente des antécédents obstétricaux vasculaires.…”