title: A correlation of erythrokinetics, ineffective erythropoiesis, and erythroid precursor apoptosis in thai patients with thalassemia.
abstract: The variety of patients with thalassemia in Thailand offers an opportunity to fully characterize the kinetic causes of the anemia and to study apoptosis of marrow erythroid precursors as a possible factor contributing to its severity. Kinetic studies showed that in hemoglobin H (HbH) disease, the extent of hemolysis, as well as the minimally ineffective erythropoiesis, usually falls within the compensatory capacity of normal erythropoiesis; therefore, anemia in patients with HbH partly represents a failure to expand erythropoiesis adequately. Hemoglobin Constant Spring (HbCS), a common variant of alpha thalassemia in Bangkok, causes more severe hemolysis and a distinct increase in ineffective erythropoiesis. Ineffective erythropoiesis plays a much more prominent role in beta thalassemia/hemoglobin E (beta-thal/HbE) disease, in which the variability of the anemia is puzzling. We compared mild and severe cases and found that patients with severe disease had a maximal marrow erythropoietic response that failed to compensate for very short survival of red blood cells and a marked quantitative increase in ineffective erythropoiesis. Analysis of apoptosis of marrow erythroid precursors done both on shipped samples and in Bangkok showed a moderate increase in HbH disease, consistent with the small increase in ineffective erythropoiesis. In patients with homozygous HbCS, there was a further increase in apoptosis, consistent with the additional increase in ineffective erythropoiesis. Patients with beta-thal/HbE disease had the most ineffective erythropoiesis and the most erythroid apoptosis. Thus, it appears that alpha-chain deposition in erythroid precursors, either alpha(A) or alpha(cs), leads to accelerated apoptosis and ineffective erythropoiesis.
authors.affiliation: Thalassemia Research Center, Institute of Sciences and Technology for Research and Development, Mahidol University, Salaya Campus, Nakornprathom, Thailand.
authors.forename: P
authors.initials: P
authors.lastname: Pootrakul
authors.forename: P
authors.initials: P
authors.lastname: Sirankapracha
authors.forename: S
authors.initials: S
authors.lastname: Hemsorach
authors.forename: W
authors.initials: W
authors.lastname: Moungsub
authors.forename: R
authors.initials: R
authors.lastname: Kumbunlue
authors.forename: A
authors.initials: A
authors.lastname: Piangitjagum
authors.forename: P
authors.initials: P
authors.lastname: Wasi
authors.forename: L
authors.initials: L
authors.lastname: Ma
authors.forename: S L
authors.initials: SL
authors.lastname: Schrier
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D001853:Bone Marrow / Q000473:pathology; D004905:Erythrocyte Aging; D015672:Erythroid Precursor Cells / Q000473:pathology*; D004920:Erythropoiesis; D006446:Hemoglobin E / Q000032:analysis; D006455:Hemoglobins, Abnormal / Q000032:analysis; D006461:Hemolysis; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D013785:Thailand; D013789:Thalassemia / Q000097:blood*; D017085:alpha-Thalassemia / Q000097:blood; D017086:beta-Thalassemia / Q000097:blood
chemical_list: D006455:Hemoglobins, Abnormal; D006446:Hemoglobin E; C035541:Hemoglobin Constant Spring