Calcium and
sodium permeability of erythrocytes from patients with untransfused alpha- or
beta- thalassemia major has been studied and compared to mature erythrocytes or control cells with comparable
reticulocytosis. Isotopic Na(+) influx was increased a mean fourfold greater than normals and threefold greater than reticulocyte rich control. Passive net leak of Na(+) into thalassemic cells incubated with
ouabain was also increased corresponding to their greater (22)Na(+) influx. Erythrocyte Na(+) and K(+) concentrations and cell water content per unit volume of cells were normal. Quantitation of active
cation pumps in the cell membrane by the technique of [(3)H]
ouabain binding showed a 2.6- to 9.9-fold increase above normal. Inward Ca(2+) movement was studied in cells with absent Ca(2+) pumping produced by depletion of either
ATP or Mg(2+)-
ions.
Calcium uptake by
ATP depleted thalassemic cells was increased 12-fold above normals and 3.6-fold above reticulocyte-rich controls. The Ca(2+) uptake by Mg(2+)-depleted thalassemic cells was also increased above normal confirming that erythrocyte Ca(2+) permeability is increased in this disease. Osmotic fragility measurements show that the surface area to volume ratio of thalassemic erythrocytes was increased by 15 to 25% above mature erythrocytes. The increased passive
cation permeability of thalassemic erythrocytes cannot be explained by either
reticulocytosis or an increased surface area to volume ratio of these cells. Moreover, erythrocyte Na(+) and Ca(2+) influxes in
congenital dyserythropoietic anemia (CDA type 2) were increased 2- and 14-fold, respectively, above normal. The increased
cation fluxes and
cation pump numbers in thalassemic and
congenital dyserythropoietic anemia erythrocytes are consistent with the hypothesis of membrane immaturity arising from rapid marrow transit times, a concept previously advanced to explain the persistence of
i-antigen on these cells.