Studies of erythropoietic cells in heterozygotes and homozygotes for haemoglobin Constant Spring and in heterozygotes for both haemoglobin Constant Spring and alpha-thalassaemia 1 trait: extent of globin chain precipitation and cell cycle distribution.

Abstract

Electron microscope studies revealed that the average value for the percentage of erythropoietic cell profiles containing globin chain precipitates in heterozygotes for haemoglobin Constant Spring (HbCS) was similar to that in subjects with alpha-thalassaemia 2 trait and that the average values for this parameter in homozygotes for HbCS and patients with HbCS-H disease were similar to that in individuals with HbH disease. The explanation for the finding that the presence of two alpha cs genes (in homozygotes for HbCS) caused a degree of precipitation corresponding to that seen in patients with HbH disease, who have three deleted alpha genes, rather than to that seen in individuals with alpha-thalassaemia 1 trait, who have two deleted alpha genes, is uncertain. In all the patients with HbCS studied, the majority of the inclusions of precipitated globin chains had a stellate or branching appearance and were considered to consist of beta-chains. However, in the homozygotes for HbCS and to a lesser extent in the patients with HbCS-H disease there were small but significant numbers of erythropoietic cell profiles containing multiple rounded inclusions of the type seen in the beta-thalassaemia syndromes, or both branching and multiple rounded inclusions. It is argued that these rounded inclusions probably consisted either of precipitated HbCS or beta-chains rather than alpha-chains. The distribution of erythroblasts in the different stages of the cell cycle was normal in two homozygotes for HbCS and two patients with HbCS-H disease, indicating that there was little or no cell death during the proliferative phase of erythropoiesis in either of these conditions.