A correlation of erythrokinetics, ineffective erythropoiesis, and erythroid precursor apoptosis in thai patients with thalassemia

Blood. 2000 Oct 1;96(7):2606-12.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Apoptosis*
  • Bone Marrow / pathology
  • Erythrocyte Aging*
  • Erythroid Precursor Cells / pathology*
  • Erythropoiesis*
  • Hemoglobin E / analysis
  • Hemoglobins, Abnormal / analysis
  • Hemolysis
  • Humans
  • Kinetics
  • Middle Aged
  • Thailand
  • Thalassemia / blood*
  • alpha-Thalassemia / blood
  • beta-Thalassemia / blood


  • Hemoglobins, Abnormal
  • Hemoglobin E
  • Hemoglobin Constant Spring