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

The variety of patients with thalassemia in Thailand offers an opportunity to fully characterize the kinetic causes of the anemia and to study apoptos is of marrow erythroid precursors as a possible factor contributing to its severity. Kinetic studies showed that in hemoglobin H (HbH) disease, the ex tent of hemolysis, as well as the minimally ineffective erythropoiesis, usu ally falls within the compensatory capacity of normal erythropoiesis; there fore, anemia in patients with HbH partly represents a failure to expand ery thropoiesis adequately. Hemoglobin Constant Spring (HbCS), a common variant of or 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) d isease, in which the variability of the anemia is puzzling. We compared mil d and severe cases and found that patients with severe disease had a maxima l marrow erythropoietic response that failed to compensate for very short s urvival of red blood cells and a marked quantitative increase in ineffectiv e erythropoiesis. Analysis of apoptosis of marrow erythroid precursors done both on shipped samples and in Bangkok showed a moderate increase in HbH d isease, consistent with the small increase in ineffective erythropoiesis. I n patients with homozygous HbCS, there was a further Increase in apoptosis, consistent with the additional increase in ineffective erythropoiesis. Pat ients with beta-thal/HbE disease had the most ineffective erythropoiesis an d the most erythroid apoptosis. Thus, it appears that or-chain deposition i n erythroid precursors, either alpha(A) or alpha(CS), leads to accelerated apoptosis and ineffective erythropoiesis. (Blood. 2000;96: 2606-2612) (C) 2 000 by The American Society of Hematology.