Rheology of the sickle cell disorders.
The sickling process causes secondary changes in cell shape, size, cation and water content, and membrane structure that contribute to the impairment of intrinsic cell deformability (Figure 2). This rheological defect is partially compensated by a low haematocrit, which moderates the rise in whole-blood viscosity, and by a rise in cardiac output which increases capillary flow velocity (Berger and King, 1982). A delicate balance exists between these mechanisms and any local disturbance of this balance by pathological changes in factors extrinsic to the sickle cell (Figure 2) can precipitate vaso-occlusion. There is still considerable controversy over the site (arteriolar, capillary, or venular) of vaso-occlusion, the type of sickle cell (reversibly sickled or irreversibly sickled) that is primarily involved, and the relative importance of extra-erythrocytic precipitating factors such as stasis, hypoxia, hyperosmolality, acidosis, alteration in temperature, acute-phase rise in plasma proteins and leukocytes, prothrombotic changes in coagulation factors and platelets, and adhesion of blood cells to vascular endothelium (Figure 2). A low-grade hypercoagulable state has been described in patients with SS (Leichtman and Brewer, 1978; Richardson et al, 1979) which may be related to the procoagulant effect of the shift of phosphatidyl serine to the outer lipid bilayer of the sickle cell (Chiu et al, 1981; Franck et al, 1985). Platelets appear to accumulate at sites of vaso-occlusion (Siegel et al, 1985) and their migration to the vessel wall may be enhanced by the presence of poorly deformable erythrocytes (Aarts et al, 1984). Endothelial cell damage in the arterial or venous circulation may also contribute (Klug et al, 1982). Thus vaso-occlusion appears to result from a complex interaction between blood cells, plasma proteins and endothelium and any one of several precipitating factors may disturb the fragile steady state and cause a painful crisis. The study of sickle cells by rheological methods has considerable potential for investigating the pathophysiology of vaso-occlusive episodes in the SCD and for monitoring, both in vitro and ex vivo, the efficacy of antisickling compounds. Because of the multiple intrinsic and extrinsic factors that contribute to the rheological defect, it is not yet known which of these should be the primary target for an antisickling agent. In-vitro rheological studies in which different metabolic stresses can be applied to intact sickle cells in the presence of a putative antisickling drug should help to answer this question.(ABSTRACT TRUNCATED AT 400 WORDS)