Variable deformability of irreversibly sickled erythrocytes

The relationship of altered deformability of irreversibly sickled cells (ISC) to their morphological and physiologic characteristics was evaluated in this study. ISC obtained by differential centrifugation and density gradient sedimentation were separated and enriched into hard and soft populations on the basis of their ability to pass through Nuclepore filters with an average pore size of 3.0 mu. Measurement of deformability by micropipette and Nuclepore elastimetry documented marked differences of erythrocyte rigidity in the two populations. Yet ISC morphology, intracellular viscosity determinants (mean cell hemoglobin concentration, density profile gradient, hemoglobin composition), and surface area geometry (mean cell volume, osmotic fragility) were similar in populations of hard and soft ISC. The similarity in intracellular viscosity and surface area geometry suggests that an intrinsic membrane alteration is responsible for the difference in deformability of filtration separated populations of ISC. Hard ISC may be more important to the pathophysiology of sickle cell disease than soft ISC, though ISC counts on peripheral blood smears would not be of help in distinguishing the two populations.