Solid-like behaviour of unsheared sickle haemoglobin gels and the effects of shear

Pathogenesis in sickle cell disease depends on the polymerization of deoxyhaemoglobin S into long fibres followed by 'gel' formation. The 'gelation' renders the affected erythrocytes less deformable than normal so that they obstruct the microvasculature and the 'gelation' process has been one of the targets for the development of therapeutic treatments of sickle cell disease. 'Gelation', however, acts through the rheological properties it induces and rheological abnormalities are therefore the immediate bases of pathogenesis. Although there has been very little study of the rheology of haemoglobin S haemolysates, the 'gels' are generally considered to be highly viscous and thixotropic on the basis of gross observation. Limited and generally qualitative observations show that high viscosity depends on deoxygenation^1,2 and exhibits hysteresis in gelling/ungelling cycles¹; also that shearing accelerates gelation^3,4 and can induce formation of fibre aggregates and crystals in suspension which, in contrast to the 'gel', are fluid⁵. Using transient and steady state methods it is shown here that unsheared sickle deoxyhaemoglobin preparations are solid-like, consistent with a gellike nature, whereas shearing converts them to thixotropic viscous systems. These results underline the marked variation and thixotropy the system can undergo and may be relevant to the pathogenesis, clinical course and therapy of sickle cell disease.