Thromboxane and prostacyclin in maternal and fetal circulation in pre-eclampsia

Abstract

Objectives: A major pathophysiologic change of pre-eclampsia has been attributed to the overproduction of thromboxane A 2 (TXA 2) mainly from activated platelets. On the other hand, increased biosynthesis of TXA 2 has also been reported from preeclamptic placentas. The systemic role of these different sources of TXA 2 has not been clarified. The purpose of this study is to define the changes of TXA 2 and the antagonizing prostacyclin (PC) in maternal and fetal circulations. Methods: The stable metabolites of TXA 2 and PC [Thromboxine B 2 (TXB 2) and 6-keto-prostaglandin F 1α (6-keto-PGF 1α), respectively] in the cord and maternal blood of nine patients with pre-eclampsia and nine normal parturients were measured by radioimmunoassay. Result: In normal pregnancy, the cord blood contained much higher TXB 2 (1697±898 vs. 267±128 ng/ml, P<0.01) and 6-keto-PGF 1α (266±263 vs. 12.5±3.9 ng/ml, P<0.05) levels than the maternal blood. In the preeclamptic state, a marked increase of TXB 2 was noted in both maternal and cord blood, reaching levels which were significantly higher than during normal pregnancy (2995±1103 vs. 267±128 ng/ml in maternal blood, P<0.0001, and 3197±1288 vs. 1697±898 ng/ml in cord blood, P<0.005). A less significant increase in 6-keto-PGF 1α (134±10.8 vs. 12.5±3.9 ng/ml, P<0.05) was also noted in the maternal blood. Moreover, the level of TXB 2 correlated with the diastolic blood pressure of preeclamptic patients before and after delivery. Conclusion: The results suggest an abundant source of eicosanoids in the feto-placental circulation, which does not readily cross the placental barrier. In pregnancy complicated with pre-eclampsia, thromboxane level of both fetal and maternal circulations are markedly increased, which may be responsible for the pathophysiologic changes. The lack of adverse systemic effects on the fetus highlights a placental source of TXA 2 of transient bioactivity which is rapidly hydrolyzed to non-active TXB 2.