Blood, 15 November 2001, Vol. 98, No. 10, pp. 2885-2886
Hereditary spherocytosis: back to the
reticulocytes
Da Costa and colleagues (page 2894) shed new light on the
chronology of membrane area loss in 2 hemolytic disorders, hereditary spherocytosis (HS) and autoimmune hemolytic anemia (AIHA). By cleverly
combining the time-honored measurements of osmotic fragility and a
contemporary flow cytometric assay of both erythrocytes and
reticulocytes, Da Costa et al were able to directly measure critical
hemolytic volume and, thus, cell surface area of both reticulocytes and
mature erythrocytes in normal blood, HS blood, and AIHA
blood.
Their studies reveal that maturation of normal
reticulocytes into erythrocytes is associated with the loss of
approximately 9 µm2 of surface area (from 142.4 ± 2.0
to 133.6 ± 3.0) and that the spleen plays a major role in this
process. In HS, a marked reduction in the surface area of reticulocytes
was noted while the reduction of surface area associated with
maturation into erythrocytes was the same as that of normal cells.
Thus, contrary to the general belief that surface area loss in
HS is a gradual process occurring during the shortened lifetime of
erythrocytes, Da Costa et al demonstrate that surface area loss occurs
very early at the reticulocytes stage and is also not affected by
splenectomy. In AIHA, membrane surface loss is not evident at the
reticulocyte stage and occurs only in mature erythrocytes. While
great progress has been made on understanding the molecular nature of
HS, the pathophysiology of this disease is still unclear. This study
resets the clock of membrane surface loss in HS back to the
reticulocyte stage: how are reticulocytes losing cell membrane so early
and what is the underlying process still remain to be defined.
But this study identifies HS as a paradigm of a potentially novel
category of anemias due to "reticulocyte" membrane diseases.
Carlo Brugnara
Children's Hospital, Harvard
