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. (N Engl J Med 299:1428–1435, 1978) THE origins of the increased level of fetal hemoglobin (HbF) evident in most patients with sickle-cell anemia have not been well defined. It has been unclear to what extent such increase is due to selective production of HbF-bearing red blood cells (F cells) and possibly enhanced biosynthesis of HbF within them and to what extent it is a reflection of HbF-based resistance to sickling²³ and consequent preferential survival of F cells. Although there is little doubt that HbF production is increased beyond the normal adult limit in some homozygotes for sickle-cell hemoglobin (HbS)⁴ and that F-cell survival is selectively prolonged.