The sequence of pathogenic events in sickle cell disease begins with the genetic abnormality and proceeds through molecular and red cell abnormalities to clinical events of vascular obstruction, hemolysis, and crisis. The least studied event, central in the sequence, is altered viscosity and rheology of the gelled deoxyhemoglobin S. In this work, shear is shown not only to measure the formation of gels, but to alter the progress of gelation. Thus, intraerythrocytic shear may be an important factor in pathogenesis. Increasing shear decreases the delay time for gelation as measured directly and by experiments in which shear rate is altered during the delay period. After the delay time, during the growth stage, characterized by a large increase in viscosity, shearing increases the rate of viscosity increase. On the other hand, as previously shown, shearing breaks down solid-like gels. These two effects of shear, one detrimental and the other possibly beneficial, may contribute to the variations known to exist in the clinical picture of sickle cell disease. The growth stage progress curve of gelation is here shown to he exponential in shape. This suggests that fiber breakage occurs under shear and/or that new fibers nucleate on the surface of existing fibers (i.e. heterogeneous nucleation). Finally, the progress curve is shown to be composed of plastic (i.e. solid-like) as well as viscous components early in gel development.
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health