The pleiotropic effects of α-thalassemia on HbSS and HbSC sickle cell disease: reduced erythrocyte cation co-transport activity, serum erythropoietin and transfusion burden do not translate into increased survival
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Authors
Brewin, John N.
Nardo‐Marino, Amina
Stuart‐Smith, Sara
El Hoss, Sara
Hanneman, Anke
Strouboulis, John
Menzel, Stephan
Gibson, John S.
Rees, David C.
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Issue Date
2022
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Article
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Abstract
α-Thalassemia is one of the most important genetic modulators of sickle cell disease (SCD). Both beneficial and detrimental effects have been described previously. We use a 12-year data set on a large cohort of patients with HbSS (n = 411) and HbSC (n = 146) to examine a wide range of these clinical and laboratory associations. Our novel findings are that α-thalassemia strongly reduces erythrocyte potassium chloride co-transporter (KCC) activity in both HbSS and HbSC (p = .035 and p = .00045 respectively), suggesting a novel mechanism through which α-thalassemia induces a milder phenotype by reducing red cell cation loss. This may be particularly important in HbSC where reduction in mean cell hemoglobin concentration is not seen and where KCC activity has previously been found to correlate with disease severity. Additionally, we show that α-thalassemia not only increases hemoglobin in patients with HbSS (p = .0009) but also reduces erythropoietin values (p = .0005), demonstrating a measurable response to improved tissue oxygenation. We confirm the reno-protective effect of α-thalassemia in patients with HbSS, with reduced proteinuria (p = .003) and demonstrate a novel association with increased serum sodium (p = .0004) and reduced serum potassium values (p = 5.74 × 10
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American Journal of Hematology
Volume
97
Issue
10