A correlation of erythrokinetics, ineffective erythropoiesis, and erythroid precursor apoptosis in Thai patients with thalassemia: Presented in part at the XXI Congress of the International Society of Hematology, Sydney, Australia, May 1985, and the Annual Meeting of the American Society of Hematology, San Diego, CA, December 1997.

Abstract

AbstractThe 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 α thalassemia in Bangkok, causes more severe hemolysis and a distinct increase in ineffective erythropoiesis. Ineffective erythropoiesis plays a much more prominent role in β thalassemia/hemoglobin E (β-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 β-thal/HbE disease had the most ineffective erythropoiesis and the most erythroid apoptosis. Thus, it appears that α-chain deposition in erythroid precursors, either αA or αcs, leads to accelerated apoptosis and ineffective erythropoiesis.