Sickle cell disease: The physical chemical bases of pathogenesis

At present there is no specific treatment for sickle cell disease. However, a great deal is known about the molecular abnormality that produces the disease and the highly abnormal physical chemical events directly responsible for its pathogenesis. This review outlines the physical chemistry associated with sickle cell disease and its connection with the clinical pathology, and suggests how that knowledge may lead to advances in treatment and perhaps to a specific therapy for the disease. The recent rapid advances in the understanding of basic events in sickle cell disease center on three areas: The kinetics of gelation, which is the fundamental pathogenic process; the equilibria of gelation; and the structure of the gel and the fibers which comprise it. These events are finely balanced: Small changes in solution conditions can, through cooperativity or through alteration of kinetic path, produce large changes in the rates and/or results of gelation. A deeper understanding of these events could lead to advances in treatment with or without the development of a site-specific reagent that inhibits gelation by reacting with the hemoglobin S molecule.