Erythroid bone marrow activity and red cell hemoglobinization in iron-sufficient β-thalassemia heterozygotes as reflected by soluble transferrin receptor and reticulocyte hemoglobin content. Correlation with genotypes and Hb A2 levels

631 Background and Objectives. Ferrokinetic studies and erythroid cell ultrastructural studies have indicated some degree of ineffective erythropoiesis in heterozygous β-thalassemia, although a wide case-to-case variation was observed. In this study we applied rapid biochemical and hematologic measurements to assess erythroid marrow activity (sTfR) and reticulocyte hemoglobin content (CHr) in iron-sufficient individuals with heterozygous β-thalassemia and investigated the correlation with the degree of globin polypeptide chain imbalance by comparing parameters between β-thalassemia heterozygotes with genotypes of variable severity. Design and Methods. We studied 57 iron-sufficient adults with heterozygous β-thalassemia, divided into groups according to genotype: group A, βsilent-thalassemia heterozygotes, group B, β+-thalassemia heterozygotes and group C, β0-thalassemia heterozygotes. Twenty-one hematologically normal individuals served as controls (group D). We measured hematologic parameters including CHr with a Bayer-Advia 120 hematology analyzer. Hemoglobins were analyzed by high performance liquid chromatography, while biochemical parameters of iron status (iron, ferritin, transferrin and sTfR) were measured with chemical, luminometric and nephelometric methods. Results. We found significant positive correlations between sTfR values for all β-thalassemia heterozygote groups when plotted against Hb A2 and Hb F levels (r=0.566, p<0.0001 and r=0.283, p<0.03, respectively) and a significantly negative correlation between CHr and Hb A2 values (r=-0.790, p<0.00001). These data reflect the fine association of globin polypeptide chain imbalance with erythron expansion and the greater degree of ineffective erythropoiesis in β-thalassemia heterozygotes with more severe genotypes. Interpretation and Conclusions. This study is the first demonstration that sTfR and CHr are useful parameters for evaluating the relative severity of different genotypes in heterozygous β-thalassemia.