Why are hemoglobin F levels increased in HbE/beta thalassemia?
Weatherall D., Porter JB., Clegg JB., Rees DC.
To try to further define the mechanisms that increase the levels of hemoglobin F (HbF) in the blood of patients with severe forms of beta thalassemia, we have studied two comparable populations of hemoglobin E (HbE)/beta thalassemics, one regularly transfused and one receiving only occasional blood transfusions. Regular transfusion was associated with a significant decrease in soluble transferrin receptor and erythropoietin levels. Globin chain synthesis studies also show a highly significant decrease in HbF synthesis relative to HbE in the transfused patients. This effect was confirmed by sequential data on one patient, studied before and after the commencement of regular blood transfusion; blood transfusion was followed by a marked increase in the alpha/gamma, beta(E)/gamma, and HbE/HbF ratios. These data suggest that the high HbF levels in HbE/beta thalassemia, and other beta thalassemia syndromes, result from increased erythropoietin levels leading to bone marrow expansion, and possibly increased F-cell production, combined with ineffective erythropoiesis giving a survival advantage to F cells. This study 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.