Prostacyclin, thromboxane and glomerular filtration rate are abnormal in sickle cell pregnancy.

Opeyemi Abayomi Obilade,Fiona Broughton Pipkin,Alani Suleimon Akanmu,Bosede Bukola Afolabi

doi:10.1371/journal.pone.0184345

Opeyemi Abayomi Obilade, Fiona Broughton Pipkin + Show 2 more

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https://doi.org/10.1371/journal.pone.0184345

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Abstract

BackgroundPregnancy increases the risk of morbidity and mortality in sickle cell disease. We previously showed pregnant women with sickle cell disease to have a relatively low plasma renin concentration in late pregnancy, associated with a lack of the expected plasma volume expansion. We hypothesized this to be due to increased systemic vascular resistance through an imbalance between the vasodilator prostacyclin and vasoconstrictor thromboxane, associated with decreased glomerular filtration rate (GFR).ObjectiveTo compare estimated prostacyclin, thromboxane and GFR in non-pregnant and pregnant women with hemoglobin SS (HbSS) and AA (HbAA).Study designFour groups of 20 normotensive, nulliparous women were studied in Lagos, Nigeria: pregnant HbSS or HbAA women at 36–40 weeks gestation; non-pregnant HbSS and HbAA controls. We measured stable metabolites of prostacyclin and thromboxane A2 by enzyme-linked immunosorbent assay; GFR using the Cockcroft-Gault equation. Data analysis was by independent (Student’s) t-test or Mann-Whitney U test for comparisons between any two groups of continuous variables, univariate ANOVA for multiple groups and Pearson’s correlation coefficient for degree of association between variables.ResultsHbSS women had lower serum 6-keto-PGF1α concentrations than HbAA, whether pregnant or non-pregnant (P<0.001; P<0.004 respectively). Conversely, pregnant HbSS women had higher serum TxB2 (P<0.001); non-pregnant HbSS women had non-significantly higher TxB2 concentrations. The 6-keto-PGF1α:TxB2 ratio was markedly increased (pro-vasodilatory) in HbAA pregnancy (P<0.001) but reduced in HbSS pregnancy (P = 0.037). GFRs (mL/min) were higher in non-pregnant HbSS than HbAA (P<0.008) but only marginally raised in HbSS women in late pregnancy (P = 0.019) while markedly raised in HbAA pregnancy (P<0.001).ConclusionThe lower ratio of prostacyclin-thromboxane metabolites in HbSS pregnancy may indicate endothelial damage and an increased tendency to vasoconstriction and clotting. If confirmed by subsequent longitudinal studies, interventions to increase prostacyclin and reduce thromboxane, such as low dose aspirin, may be potentially useful in their management.

Highlights

BackgroundPregnancy increases the risk of morbidity and mortality in sickle cell disease
Sickle cell disease is a hemoglobinopathy that presents with various complications due to chronic anemia, hemolysis and occlusion of small vessels [1, 2]
Plasma volume (PV) rises early in the first trimester and plateaus at about 34 weeks’ gestation. This ~50% rise [6, 7] is associated with improved uteroplacental perfusion, oxygenation, and good fetomaternal outcomes [8, 9]; poor plasma volume (PV) expansion is associated with poor outcomes such as preeclampsia and fetal growth restriction [10, 11]

Summary

Background

Pregnancy increases the risk of morbidity and mortality in sickle cell disease. We previously showed pregnant women with sickle cell disease to have a relatively low plasma renin concentration in late pregnancy, associated with a lack of the expected plasma volume expansion. We hypothesized this to be due to increased systemic vascular resistance through an imbalance between the vasodilator prostacyclin and vasoconstrictor thromboxane, associated with decreased glomerular filtration rate (GFR)

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