losartan-potassium and Hemoglobin-SC-Disease

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

Topics: alpha-Thalassemia; Anemia, Sickle Cell; Cations; Erythrocytes; Erythropoietin; Hemoglobin SC Disease; Hemoglobin, Sickle; Humans

Topics: Erythropoietin; Female; Hemoglobin SC Disease; Humans; Middle Aged; Multiple Organ Failure

The ability of circulating progenitor cells to develop erythroid colonies was studied in vitro in the presence or absence of growth factors (5637-CM and erythropoietin) in 63 patients with sickle cell disease (SCD) (36 homozygotes for hemoglobin [Hb] S, 13 double heterozygotes for Hb S and beta thalassemia, and 14 SC patients) in Southeast Brazil. In the presence of growth factors, SCD patients (all genotypes) presented significantly higher numbers of circulating burst-forming unit-erythroid (BFU-E/5 x 10(5) MNC), when compared with control subjects. However, when the progenitor cells were cultured in the absence of added stimulus, high numbers of BFU-E were observed only in the genotypes SS and S/beta thalassemia. SC patients presented a similar response to the control subjects. Moreover, there was an inverse correlation between spontaneous (without stimulus) BFU-E and Hb levels in SCD patients. These results suggest that the formation of spontaneous BFU-E observed in SCD may be due to an expanded erythropoiesis secondary to hemolysis.

Topics: Adult; Anemia, Sickle Cell; beta-Thalassemia; Brazil; Cell Differentiation; Cell Division; Colony-Forming Units Assay; Erythroid Precursor Cells; Erythropoietin; Genotype; Hemoglobin SC Disease; Humans; Recombinant Proteins; Sickle Cell Trait