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

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 hypothesi...

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Main Authors: Obilade, Opeyemi Abayomi, Akanmu, Alani Suleimon, Broughton Pipkin, Fiona, Afolabi, Bosede Bukola
Format: Article
Published: Public Library of Science 2017
Online Access:https://eprints.nottingham.ac.uk/47005/
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author Obilade, Opeyemi Abayomi
Akanmu, Alani Suleimon
Broughton Pipkin, Fiona
Afolabi, Bosede Bukola
author_facet Obilade, Opeyemi Abayomi
Akanmu, Alani Suleimon
Broughton Pipkin, Fiona
Afolabi, Bosede Bukola
author_sort Obilade, Opeyemi Abayomi
building Nottingham Research Data Repository
collection Online Access
description 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). OBJECTIVE: To compare estimated prostacyclin, thromboxane and GFR in non-pregnant and pregnant women with hemoglobin SS (HbSS) and AA (HbAA). STUDY DESIGN: Four 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. RESULTS: HbSS 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). CONCLUSION: The 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.
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spelling nottingham-470052024-08-15T15:23:57Z https://eprints.nottingham.ac.uk/47005/ Prostacyclin, thromboxane and glomerular filtration rate are abnormal in sickle cell pregnancy Obilade, Opeyemi Abayomi Akanmu, Alani Suleimon Broughton Pipkin, Fiona Afolabi, Bosede Bukola 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). OBJECTIVE: To compare estimated prostacyclin, thromboxane and GFR in non-pregnant and pregnant women with hemoglobin SS (HbSS) and AA (HbAA). STUDY DESIGN: Four 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. RESULTS: HbSS 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). CONCLUSION: The 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. Public Library of Science 2017-09-07 Article PeerReviewed Obilade, Opeyemi Abayomi, Akanmu, Alani Suleimon, Broughton Pipkin, Fiona and Afolabi, Bosede Bukola (2017) Prostacyclin, thromboxane and glomerular filtration rate are abnormal in sickle cell pregnancy. PLoS ONE, 12 (9). e0184345. ISSN 1932-6203 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0184345 doi:10.1371/journal.pone.0184345 doi:10.1371/journal.pone.0184345
spellingShingle Obilade, Opeyemi Abayomi
Akanmu, Alani Suleimon
Broughton Pipkin, Fiona
Afolabi, Bosede Bukola
Prostacyclin, thromboxane and glomerular filtration rate are abnormal in sickle cell pregnancy
title Prostacyclin, thromboxane and glomerular filtration rate are abnormal in sickle cell pregnancy
title_full Prostacyclin, thromboxane and glomerular filtration rate are abnormal in sickle cell pregnancy
title_fullStr Prostacyclin, thromboxane and glomerular filtration rate are abnormal in sickle cell pregnancy
title_full_unstemmed Prostacyclin, thromboxane and glomerular filtration rate are abnormal in sickle cell pregnancy
title_short Prostacyclin, thromboxane and glomerular filtration rate are abnormal in sickle cell pregnancy
title_sort prostacyclin, thromboxane and glomerular filtration rate are abnormal in sickle cell pregnancy
url https://eprints.nottingham.ac.uk/47005/
https://eprints.nottingham.ac.uk/47005/
https://eprints.nottingham.ac.uk/47005/