Why are hemoglobin F levels increased in HbE/beta thalassemia?

To try to further define the mechanisms that increase the levels of hemoglo bin F (HbF) in the blood of patients with severe forms of beta thalassemia, we have studied two comparable populations of hemoglobin E (HbE)/beta thal assemics, one regularly transfused and one receiving only occasional blood transfusions, Regular transfusion was associated with a significant decreas e in soluble transferrin receptor and erythropoietin levels. Globin chain s ynthesis studies also show a highly significant decrease in HbF synthesis r elative to HbE in the transfused patients, This effect was confirmed by seq uential data on one patient, studied before and after the commencement of r egular blood transfusion; blood transfusion was followed by a marked increa se in the alpha/gamma, beta(E)/gamma, and HbE/HbF ratios, These data sugges t that the high HbF levels in HbE/beta thalassemia, and other beta thalasse mia syndromes, result from increased erythropoietin levels leading to bone marrow expansion, and possibly increased F-cell production, combined with i neffective erythropoiesis giving a survival advantage to F cells. This stud y also suggests that alteration in blood transfusion regimes must be taken into account when interpreting changes in HbF levels seen in trials of HbF- promoting drugs. (C) 1999 by The American Society of Hematology.