Serial microscopic immunodiffusion assays of F cells, i.e., erythrocytes that contain fetal hemoglobin (HbF), in four individuals recovering from anemia demonstrate initial increases in the percentage of circulating reticulocytes that contain HbF (F reticulocytes) and subsequent increases in the percentage of mature erythrocytes that contain HbF (F erythrocytes). In one individual responding to therapy for iron-deficiency anemia, the average percentage of F reticulocytes increased from 4.8 ± 1.1 to 16.0 ± 2.8% (mean ± SD), while the mean level of F erythrocytes increased from 3.5 ± 0.7 to 7.2 ± 0.6%. Two normal children with transient erythroblastopenia exhibited F reticulocyte percentages of 71.3 ± 6.7 and 41.5 ± 1.5%, respectively, when erythropoiesis resumed. With recovery these values fell to finally measured values of 33.7 ± 4.7 and 12.6 ± 1.1%, respectively. In an adolescent with sickle cell anemia, F-reticulocyte percentages fluctuated between 0.6 ± 1.1 and 34.0 ± 2.8% and paralleled the rise and fall of total reticulocytes associated with therapy for a nasopharyngeal carcinoma. Such findings suggest that first, the production of F cells and non-F cells are separately regulated. Second, F-cell production is preferentially stimulated during escape from erythropoietic suppression and selectively depressed at the start of suppression. Third, during escape from erythropoietic suppression, F-cell production in vivo resembles that reported for in vitro cultures of erythroid stem cells. Fourth, individuals with sickle cell anemia, like individuals without hemoglobinopathies, can change their relative level of F-cell production.
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