Temporal differences in membrane loss lead to distinct reticulocyte features in hereditary spherocytosis and in immune hemolytic anemia

Spherocytic red cells with reduced membrane surface area are a feature of h ereditary spherocytosis (HS) and some forms of autoimmune hemolytic anemia (AIHA). It is generally assumed that membrane loss in spherocytic red cells occurs during their sojourn in circulation. The structural basis for membr ane loss in HS is improper assembly of membrane proteins, whereas In AIHA i t is due to partial phagocytosis of circulating red cells by macrophages. A hypothesis was formed that these different mechanisms should lead to tempo ral differences in surface area loss during red cell genesis and during soj ourn in circulation in these 2 spherocytic syndromes. It was proposed that cell surface loss could begin at the reticulocyte stage In HS, whereas surf ace area loss in ANA involves only circulating mature red cells. The validi ty of this hypothesis was established by documenting differences in cellula r features of reticulocytes in HS and AIHA. Using a novel technique to quan titate cell surface area, the decreased membrane surface area of both retic ulocytes and mature red cells in HIS compared with normal cells was documen ted. In contrast, in AIHA only mature red cells but not reticulocytes exhib ited decreased membrane surface area. These data imply that surface area lo ss in HS, but not In ANA, is already present at the circulating reticulocyt e stage. These findings imply that loss of cell surface area is an early ev ent during genesis of HS red cells and challenge the existing concepts that surface area loss in HS occurs predominantly during the sojourn of mature red cells in circulation. (C) 2001 by The American Society of Hematology.