Prostacyclin, thromboxane A2 and the effect of low-dose ASA in pregnancies at high risk for hypertensive disorders

Abstract

Background. The aim of this study was to investigate the prostanoid production in pregnancies at high risk for hypertensive disorders, and the effect of low-dose acetyl-salicylic acid (ASA) on prostanoids. Material and methods. Ninety women with a bilateral notching in uterine arteries screened by Doppler ultrasound at 12-14 gestational weeks were randomized to the ASA (0.5mg/kg/day) or placebo group. Forty-three women in both groups were followed up through-out the pregnancy. Urine samples were taken at baseline, and at 24-26 and 32-34 weeks of gestation to determine the urinary 11-dehydrothromboxane B2 (u-11-dehydro-TxB2) and 2,3-dinor-6-keto-prostaglandin F1α(u-2,3-dinor-6-keto-PGF1α), the metabolites of thromboxane A2 and prostacyclin, respectively. Results. In the pregnancies with pregnancy-induced hypertension (PIH) before 37 gestational weeks, the 2,3-dinor-6-keto-PGF1α/11-dehydro-TxB2 ratio did not increase as much as in other pregnancies (P = 0.028). In the placebo group pregnancies with preeclampsia had significantly lower 2,3-dinor-6-keto-PGF1α (P = 0.019) at 12-14 weeks of gestation compared to other pregnancies. In the placebo group the 2,3-dinor-6-keto- PGF1α/11-dehydroTxB2 ratio remained unchanged throughout the pregnancy, with no significant difference between pregnancies with a normal or an adverse outcome. In the ASA group the 2,3-dinor-6-keto- PGF1α/ 11-dehydro-TxB2 ratio increased (P < 0.001, early vs. midpregnancy). Again, the changes were similar in pregnancies with a normal or an adverse outcome. Conclusion. The balance of prostacyclin and thromboxane A2 shifted in an unfavorable direction in pregnancies complicated by PIH. ASA had a favorable effect on the prostanoids.