Red cell mechanics: what changes are needed to adversely affect in vivo circulation

The ability of red cells to deform is essential to allow their circulation. However the degree of rheological abnormality which can be tolerated before flow is impaired is not so clear. Red cell rheology has been characterised in a number of physiological, pathological and genetic conditions, and some inferences can be drawn. In vivo aging causes a small loss of cell deformability attributable to increased membrane and internal viscosity; volume and surface area are also lost. These changes cannot be sufficient to cause cellular removal, since the cells sampled had continued to circulate. In sickle cell disease, the oxygenated blood contains dense cells that are more severely abnormal than dense, aged cells from normal individuals. Melanesian ovalocytes have comparable rigidity to dense SS cells, but this condition has no marked circulatory pathology. Thus circulatory problems in SS disease probably stem from deoxygenation-induced sickling which causes extreme loss of deformability, rather than from the abnormal cells in oxygenated blood. In falciparum malaria, immature parasites cause appreciable loss of deformability but continue to circulate. Maturation of the parasites causes much greater rheological changes, including attachment to vascular endothelium, and the cells cease to circulate. In summary, quite marked changes in cell mechanics can occur without loss of ability to circulate. It thus seems that slight rheological alterations reported in some clinical studies are unlikely to cause appreciable flow disruption.