Rate of Sickling of Red Cells during Deoxygenation of Blood from Persons with Various Sickling Disorders

Abstract

Abstract The clinical severity of various sickle hemoglobinopathies was directly related to the rate of increase of viscosity of blood during deoxygenation. The principal determinants of the rate were the concentration of hemoglobin S in the red cell and the degree of interaction between hemoglobins when more than one major type was present. There was a close correlation between the rate of change of viscosity of blood under the conditions employed and the minimum concentration of the deoxygenated hemolysate required for gelation. Hemoglobin DPunjab showed the most marked interaction with hemoglobin S and hemoglobin F the least, accounting for the striking clinical differences between S-D and S-F heterozygotes. Clinical status of the patients and rate of increase of viscosity of partially deoxygenated blood were not closely correlated with the percentage of hemoglobin S in the hemolysate, the mean corpuscular sickle hemoglobin concentration, or the solubility of the hemoglobin. The viscosity of deoxygenated blood was directly related to the proportion of sickled red cells, but filamentous forms were associated with a greater viscosity than holly leaf forms; accordingly, viscosity could not be predicted precisely from the percentage of sickled erythrocytes in a blood specimen. The viscosity of blood containing sickled erythrocytes was approximately proportional to the square of the hematocrit value, an observation of relevance in explaining the frequent occurrence of vascular occlusive manifestations in patients with certain heterozygous sickling disorders without appreciable anemia. The data of this study support the concept that all of the clinical manifestations of sickle cell disease are attributable to the consequences of intravascular sickling of erythrocytes. Clinical differences between patients whose red cells appear to be similar probably can be explained by extracorpuscular factors influencing rates of sickling.