Quantitative analysis of cellular fetal hemoglobin gamma chain messenger RNA (HbF‐γ mRNA) in maternal peripheral blood

Okuda, Tomohiro; Kinoshita, Yoshiyuki; Tamura, Takeyuki; Kato, Chikako; Kojima, Hidenori; Watanabe, Ai; Honjo, Hideo

doi:10.1002/pd.1039

Cited by 3 publications

(2 citation statements)

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“…HbF is a helical tetramer composed of a porphyrin ring and 2 attached a and g globin subunits (a 2 g 2 ) (17) encoded by a (Hb-a) and g (Hb-g) globin genes; both expressed within the placental villi (12). Compared with normal pregnancies, a 20-fold up-regulation in Hb-g in umbilical cord blood and amniotic fluid as well as increased fHbF mRNA in maternal blood occur in FGR pregnancies, implying a strong hematologic component to the disease (10,17). Indeed, as a marker of chronic fetoplacental hypoxia, increased hematocrit and erythropoiesis has been reported by several authors, but never before has it been linked to hemolytic intravascular events (11,37,38).…”

Section: Elevated Fhbf In the Fetoplacental Circulation And Heme Handmentioning

confidence: 99%

“…Although the direct impact of fHbF on the fetal circulation remains unclear, it is proposed that erythrocyte behavior is disturbed in FGR, with elevations of nucleated red cells defined in the placenta in as many as 89% of cases, even those devoid of Doppler anomalies (15,16). Although difficult to substantiate in the fetus, perpetuated erythrocytes are known to rupture under modest elevations in vascular shear stress; conditions which, without doubt are present in FGR cases, and manifest by flow abnormalities on antenatal Doppler (17). Under these circumstances, free hemoglobin release is inevitable, but under normal homeostasis remains finely regulated.…”

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confidence: 99%

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Cell free hemoglobin in the fetoplacental circulation: a novel cause of fetal growth restriction?

et al. 2018

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Cell free hemoglobin impairs vascular function and blood flow in adult cardiovascular disease. In this study, we investigated the hypothesis that free fetal hemoglobin (fHbF) compromises vascular integrity and function in the fetoplacental circulation, contributing to the increased vascular resistance associated with fetal growth restriction (FGR). Women with normal and FGR pregnancies were recruited and their placentas collected freshly postpartum. FGR fetal capillaries showed evidence of erythrocyte vascular packing and extravasation. Fetal cord blood fHbF levels were higher in FGR than in normal pregnancies ( P < 0.05) and the elevation of fHbF in relation to heme oxygenase-1 suggests a failure of expected catabolic compensation, which occurs in adults. During ex vivo placental perfusion, pathophysiological fHbF concentrations significantly increased fetal-side microcirculatory resistance ( P < 0.05). fHbF sequestered NO in acute and chronic exposure models ( P < 0.001), and fHbF-primed placental endothelial cells developed a proinflammatory phenotype, demonstrated by activation of NF-κB pathway, generation of IL-1α and TNF-α (both P < 0.05), uncontrolled angiogenesis, and disruption of endothelial cell flow alignment. Elevated fHbF contributes to increased fetoplacental vascular resistance and impaired endothelial protection. This unrecognized mechanism for fetal compromise offers a novel insight into FGR as well as a potential explanation for associated poor fetal outcomes such as fetal demise and stillbirth.-Brook, A., Hoaksey, A., Gurung, R., Yoong, E. E. C., Sneyd, R., Baynes, G. C., Bischof, H., Jones, S., Higgins, L. E., Jones, C., Greenwood, S. L., Jones, R. L., Gram, M., Lang, I., Desoye, G., Myers, J., Schneider, H., Hansson, S. R., Crocker, I. P., Brownbill, P. Cell free hemoglobin in the fetoplacental circulation: a novel cause of fetal growth restriction?

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