Regulation of fetal and adult hemoglobin formation in patients with sickle cell disease transfused to normal hematocrits.

Wit/i the technical assistance of Anne Council F ETAL HEMOGLOBIN ( Hb F) is the major respiratory pigment formed during intrauterine life. In the adult, however, only trace concentrations normally are present. In man there are at least two distinct conditions in which genetic factors cause elevated levels of Hb F in adult life. They are the hereditary persistence of fetal hemoglobin syndromes and F-thalassemia ( or Type II thalassemia).”2 It is not known why increased amounts of Hb F are sometimes associated with other clinical states, such as A2 ( or Type I) thalassemia, sickle cell anemia, aplastic anemia, leukemia, or pernicious anemia. Although marrow stress has been considered as a possible factor, there is no relation of the level of Hb F to the degree of anemia. Elevated levels of Hb F may, in fact, persist for some months following remission in aplastic anemia or pernicious anemia. ’4 The lack of immediate connection between the degree of anemia and the synthesis of increased quantities of Hb F was experimentally studied by Reed, Bradley, and Ranney in two patients with sickle cell anemia.5 They found that fetal hemoglobin synthesis persisted in spite of partial relief of the stress of anemia by the chronic administration of blood transfusion. They also found that the relative amount of Hb F in the recipients’ red cells increased during the first weeks following the institution of transfusion therapy. They considered that this finding was related solely to the more prolonged survival time of red cells containing relatively greater amounts of hemoglobin F as compared to those containing relatively greater amounts of hemoglobin S ( Hb S ).6 They did not rule out the possibility, however, that fetal hemoglobin synthesis may have continued unsuppressed by the transfusions, only that of the adult hemoglobin