Normal human erythrocytes suspended in the series of hypotonic salt solutions employed for testing red cell fragility behave like nearly perfect osmometers throughout the series, with their maximum swelling, usually around 175 per cent of their initial volume, sharply defined by their mean surface area. The same principles govern the swelling and hemolysis of some abnormal types of erythrocytes with different characteristics of abnormal fragility or resistance to osmotic hemolysis. The red cells of congenital hemolytic icterus exhibit essentially normal osmotic behavior, but since the spherocytes can swell very little within the limits of their surface area they rupture at higher tonicities, with the maximal swelling in most instances around 150 per cent of their initial volume. Thin cells are capable of greater swelling than normal cells. Moderately hypochromic erythrocytes from patients with mild anemia behaved like perfect osmometers throughout the series, to attain a maximal swelling of around 200 per cent, this value agreeing with predictions based on their mean surface area.
Erythrocytes of patients with thalassemia, sicklemia and pernicious anemia exhibited less than the expected osmometric swelling throughout the series of hypotonic solutions. The cells behaving as imperfect osmometers displayed varying patterns of hemolysis, and of maximal swelling in relation to predicted values. The increased osmotic resistance characteristic of the cells of thalassemia is accounted for by two mechanisms: they swell less than normal cells at each tonicity; and, being thin, they undergo greater swelling (around 220 per cent) before they are hemolyzed.