Elevated Levels Of Fetal Hemoglobin Research Articles

Individual variation in the production and survival of F cells in sickle-cell disease.

The protective role and underlying sources of the elevated levels of fetal hemoglobin associated with sickle-cell anemia were reassessed by microscopical immunodiffusion assays. Three variables that contribute to levels of fetal hemoglobin were examined: the percentage of fetal-hemoglobin-containing reticulocytes produced; the quantity of fetal hemoglobin synthesized within such cells; and the extent to which the fraction of fetal-hemoglobin-bearing erythrocytes is enriched beyond the level produced. Four general findings emerged from analysis of 29 patients: each variable is separately regulated; the expression of each is often distinctly different between individual patients; contrary to prior speculation, production of fetal hemoglobin may be as great in the absence of heterocellular hereditary persistence of the hemoglobin as in its presence; and fetal hemoglobin does not, as often supposed, guarantee preferential cell survival. We conclude that the differences encountered among patients must reflect heterogeneity among factors that modify production and survival of cells bearing fetal hemoglobin.

F-thalassemia: A study of thirty-one families with simple heterozygotes and combinations of F-thalassemia with A 2-thalassemia

Phenotypes of F-thalassemia are described, as revealed by a study of sixty-eight simple heterozygotes and twenty-one combinations with A 2-thalassemia. Simple heterozygotes present with typical hematologic stigmata of the thalassemia trait, elevated fetal hemoglobin levels and normal hemoglobin A 2. Double heterozygotes for F-thalassemia and A 2-thalassemia display heterogeneity in their clinical and hematologic picture, but when compared to homozygotes for A 2-thalassemia they are found to have milder clinical manifestations, less anemia and usually no transfusion requirement. Absence of hemoglobin A was observed in more than one third of double heterozygotes. Mean hemoglobin A 2 in simple heterozygotes was 50 per cent lower than in those with A 2-thalassemia trait. Elevation of fetal hemoglobin levels was observed in all but one simple heterozygote and was transmitted in a dominant pattern of inheritance. High intrafamilial similarities in the levels of hemoglobin F were documented. The data are analyzed in relation to the information on F-thalassemia thus far available. The over-all picture is that of a mutation causing defective red cell hemoglobinization, simultaneous suppression of β and δ hemoglobin chain synthesis in cis position and hereditarily determined elevation of fetal hemoglobin levels. The proposed molecular mechanisms are discussed. It is concluded that current hypotheses as to the pathogenesis of thalassemias and prevailing concepts of the regulation of hemoglobin genes cannot account for the findings in F-thalassemia.