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

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.

Natural history of blood pressure in sickle cell disease pregnancy

“…These hormonal differences were associated with decreased plasma volume expansion and increased systemic vascular resistance. 20,21 This study is limited by its retrospective, observational nature, which contributes to missing data and inconsistent blood pressure measurement techniques. However, the rate of missing data in our sample is not different between compared groups and is most associated with year of pregnancy, as a function of sites' electronic medical record transitions.…”

“…Previous studies have demonstrated abnormally low prostaglandin to thromboxane ratios during pregnancy in people with HbSS compared to unaffected pregnancies. These hormonal differences were associated with decreased plasma volume expansion and increased systemic vascular resistance 20,21 …”

Relationship between the changes in thromboxane B2, 6-keto-prostaglandin Fla, and blood glucose levels and progressive ischemic stroke

“…Progressive ischemic stroke is a common cerebrovascular disease in clinical practice, with a high morbidity and extremely high rate of fatality and disability. Progressive ischemic stroke is a serious threat to the health and life of those affected, and is a prominent disabling and fatal disease (10). For patients with acute ischemic stroke, it is essential to optimize the treatment effect and reduce the rates of disability and fatality via timely diagnosis and the formulation of targeted treatment programs.…”

Low-dose aspirin for preventing intrauterine growth restriction and pre-eclampsia in sickle cell pregnancy (PIPSICKLE): a randomised controlled trial (study protocol)

“…Even when these women do not die, a large proportion of them end up as 'maternal near miss', meaning they would have died but for prompt and appropriate intervention. 8 Choice of comparator Previously, we found a reversal in prostacyclin-thromboxane ratio in pregnant haemoglobin SS (HbSS) women, 9 a situation that is also found in non-sickle pregnancies with PE and unexplained IUGR. 10 Low-dose aspirin (LDA) has been shown to reduce the incidence of PE and IUGR in high-risk women due to its reduction of vasoconstrictor thromboxane while sparing prostacyclin, in effect correcting the ratio.…”