Blood, Vol. 92 No. 6 (September 15), 1998:
pp. 2141-2146
Is Hemoglobin Instability Important in the Interaction Between
Hemoglobin E and 
Thalassemia?
D.C. Rees,
J.B. Clegg, and
D.J. Weatherall
From the MRC Molecular Haematology Unit, Institute of Molecular
Medicine, University of Oxford, The John Radcliffe, Headington, Oxford,
UK.
Hemoglobin E (HbE;
2
226glu-lys), globally the
commonest hemoglobin variant, is synthesized at a slightly reduced rate
and has a homozygous phenotype similar to heterozygous thalassemia.
Yet, when it is inherited together with a thalassemia allele, the
resulting condition, HbE/ thalassemia, is sometimes characterized by
a severe, transfusion-dependent thalassemia major. The severity of this
interaction has not been explained. We have explored the possibility
that it may reflect the instability of HbE consequent upon globin chain
imbalance imposed by the thalassemia allele. Time-course and
pulse-chase globin chain synthesis studies at 37°C on peripheral
blood and bone marrow suggest that hemoglobin instability is not
significant in steady-state HbE/ thalassemia; this is confirmed by
density-gradient centrifugation studies that show no decrease in HbE
levels relative to HbA as HbE/+ thalassemia red blood
cells age. Globin binding to membranes was assessed and only globin
chains were found, in contrast to other unstable hemoglobins in which
both and chains were present. However, in experiments performed
on blood from HbE/ thalassemics in the temperature range 39°C to
41°C, there was evidence of instability of HbE, a finding that was
also observed in homozygous HbE. These findings suggest that the
phenotype of HbE/ thalassemia is primarily the result of the
interaction of two thalassemia alleles; however, hemoglobin
instability may be important during febrile episodes, contributing to
worsening anemia.
© 1998 by The American Society of Hematology.
