Blood, Vol. 94 No. 9 (November 1), 1999:
pp. 3199-3204
Why Are Hemoglobin F Levels Increased in HbE/
Thalassemia?
D.C. Rees,
J.B. Porter,
J.B. Clegg, and
D.J. Weatherall
From MRC Molecular Haematology Unit, University of Oxford, The
Institute of Molecular Medicine, The John Radcliffe, Headington,
Oxford, UK; and Department of Haematology, University College Hospital,
London, UK.
To try to further define the mechanisms that increase the levels of
hemoglobin F (HbF) in the blood of patients with severe forms of 
thalassemia, we have studied two comparable populations of hemoglobin E
(HbE)/ 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 
/
, E/, and
HbE/HbF ratios. These data suggest that the high HbF levels in HbE/
thalassemia, and other 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.
