Volume regulatory hormones and plasma volume in pregnant women with sickle cell disorder

Abstract

Background:Sickle cell disease (haemoglobin SS (HbSS)) mainly affects those of West African origin and is associated with hypervolaemia. Plasma volume rises by up to 50% in normal pregnancy but was previously found to be paradoxically contracted in late sickle cell pregnancy. The renin–angiotensin–aldosterone system is activated very early in human pregnancy to support the plasma volume expansion. We hypothesised that activation of the renin–angiotensin–aldosterone system would be blunted in pregnant women with sickle cell disease.Materials and methods:We measured plasma volume and concentrations of plasma renin, angiotensinogen, aldosterone and other volume-related hormones in a cross-sectional study of pregnant and non-pregnant Nigerian women with HbSS or HbAA.Results:Plasma volume was higher in non-pregnant HbSS than HbAA women, but had not risen by 16 weeks, unlike plasma volume in HbAA women. The concentration of plasma renin also rose significantly less by 16 weeks in HbSS; angiotensinogen and aldosterone concentrations increased.Conclusions:The lower plasma renin concentration at 16 weeks with HbSS could be either primary or secondary to vasoconstriction related to inadequate vasodilator activity. The contracted plasma volume might then stimulate aldosterone synthesis by non-angiotensin II dependent stimulation. Studies of vasodilators such as nitric oxide, vasodilator eicosanoids or the PlGF/VEGF/sFlT-1 axis in pregnant HbSS and HbAA women will test this hypothesis.

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

“…This pregnancy-related rise in GFR was small and not statistically significant in HbSS pregnancy, and was in fact less than 25% of the GFR increase in the HbAA pregnancy ( Table 2 ). The finding of significant blunting of the pregnancy-associated GFR increase in the pregnant HbSS, relative to HbAA pregnancy supports our previous finding of reduced PV expansion in pregnant HbSS women [ 13 ] since plasma volume and GFR tend to change in the same direction in pregnancy [ 22 ]. It also supports our hypothesis of a relative renal vasoconstriction and a reversal of the normal pregnancy vasodilatation in them.…”

“…It has been found to be reduced in preeclamptic pregnancies [ 21 , 22 ], but has not previously been examined in pregnant women with HbSS. In our previous study [ 13 ], we also found that non-pregnant HbSS women had a supranormal PV that did not change in pregnancy despite the blunted renin release, and postulated renal dysfunction to be a possible cause.…”

“…Previous studies in pregnant women with sickle cell disease have reported little or no PV expansion especially in late pregnancy, compared with their non-pregnant counterparts [ 12 , 13 ]. We have previously examined PV in the context of volume regulatory hormones including components of the renin-angiotensin-aldosterone system (RAAS) and found a relatively low plasma renin concentration in late pregnancy compared with early pregnancy, and compared with pregnant HbAA controls [ 13 ].…”

“…Previous studies in pregnant women with sickle cell disease have reported little or no PV expansion especially in late pregnancy, compared with their non-pregnant counterparts [ 12 , 13 ]. We have previously examined PV in the context of volume regulatory hormones including components of the renin-angiotensin-aldosterone system (RAAS) and found a relatively low plasma renin concentration in late pregnancy compared with early pregnancy, and compared with pregnant HbAA controls [ 13 ]. We hypothesized that pregnant HbSS women may have a generalized increase in systemic vascular resistance in late pregnancy leading to a reduction in renin synthesis or secretion and suggested that this could be due to an imbalance in vasoactive substances such as prostacyclin and thromboxane.…”

Prevalence and foetomaternal effects of iron deficiency anaemia among pregnant women in Lagos, Nigeria

“…A pregnant woman is considered to be anaemic if her haemoglobin concentration during the first and third trimester of gestation is lower than 11.0g/dL or lower than 10.5g/dL in the second trimester of pregnancy [3]. The reason for these different values, in pregnancy, is that the plasma volume expansion of 40 to 50% exceeds the 20 to 25% increase in red cell mass leading to the physiological haemodilution [4,5]. This physiologic plasma expansion has been linked to favourable pregnancy outcome [6].…”