Cellular rheology of sickle cell disease

Abstract

Homozygous sickle cell (HbSS) disease is a clinical disorder characterized by abnormal hemorheology and a variety of pathophysiologic conditions; its underlying basis is a defect in the hemoglobin molecule which leads to polymer formation at low levels of oxygen tension. Micropipette analyses of oxygenated HbSS RBC indicate increased membrane elasticity and viscosity versus normal REC, especially for irreversibly sickled cells (ISC). HbSS RBC from a given donor are heterogeneous in their mechanical properties and large donor-to-donor variations are common. The abnormal rheological properties of HbSS blood become accentuated when oxygen tension is reduced, with micropipette data indicating an exponential increase of effective membrane rigidity and the time constant for deformation as oxygen tension is lowered. However, for HbSS REC which remain discoidal and for all normal RBC, no effects of oxygen tension are observed. Presently, correlations between rheologic measurements and clinical severity are less than satisfactory, perhaps due to the hemorheological tests employed; suggestions for alternate rheologic techniques and a brief review of therapeutic approaches are presented.