title: Erythroid bone marrow activity and red cell hemoglobinization in iron sufficient beta-thalassemia heterozygotes as reflected by soluble transferrin receptor and reticulocyte hemoglobin in content. Correlation with genotypes and Hb A(2) levels.
abstract: OBJECTIVE
  Ferrokinetic studies and erythroid cell ultrastructural studies have indicated some degree of ineffective erythropoiesis in heterozygous beta-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 beta-thalassemia and investigated the correlation with the degree of globin polypeptide chain imbalance by comparing parameters between beta-thalassemia heterozygotes with genotypes of variable severity.
  
  
  METHODS
  We studied 57 iron-sufficient adults with heterozygous beta-thalassemia, divided into groups according to genotype: group A: beta(silent)-thalassemia heterozygotes, group B: beta(+)-thalassemia heterozygotes and group C: beta(0)-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 beta-thalassemia heterozygote groups when plotted against Hb A(2) and Hb F levels (r=0.566, p<0.0001 and r=0.283, p<0.03, respectively) and significantly negative correlation between CHr and Hb A(2) 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 beta-thalassemia heterozygotes with more severe genotypes.
  
  
  CONCLUSIONS
  This study is the first demonstration that sTfR and CHr are useful parameters for evaluating the relative severity of different genotypes in heterozygous beta-thalassemia.
authors.affiliation: Hematology Laboratory, First Dept. of Pediatrics, Athens University, "Aghia Sophia" Children's Hospital, Athens, Greece.
authors.forename: Christophille
authors.initials: C
authors.lastname: Skarmoutsou
authors.forename: Ioannis
authors.initials: I
authors.lastname: Papassotiriou
authors.forename: Joanne
authors.initials: J
authors.lastname: Traeger-Synodinos
authors.forename: Helene
authors.initials: H
authors.lastname: Stamou
authors.forename: Vassilios
authors.initials: V
authors.lastname: Ladis
authors.forename: Anna
authors.initials: A
authors.lastname: Metaxotou-Mavrommati
authors.forename: Alexandra
authors.initials: A
authors.lastname: Stamoulakatou
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Kanavakis
mesh_terms: D000293:Adolescent; D000328:Adult; D015672:Erythroid Precursor Cells / Q000502:physiology; D004920:Erythropoiesis; D005260:Female; D005838:Genotype; D006443:Hemoglobin A2 / Q000032:analysis*; D006454:Hemoglobins / Q000032:analysis*; D006579:Heterozygote; D006801:Humans; D007501:Iron / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011990:Receptors, Transferrin / Q000097:blood*; D012156:Reticulocytes / Q000737:chemistry*; D017086:beta-Thalassemia / Q000175:diagnosis* / Q000235:genetics
chemical_list: D006454:Hemoglobins; D011990:Receptors, Transferrin; D006443:Hemoglobin A2; D007501:Iron