This chemical reaction underlying sickling is a nucleus-mediated reaction. That is, a nucleus of about 10 hemoglobin tet-ramers has to form first, before the polymerization can start its characteristic exponential course to form sickle fibers. The formation of a nucleus is a hit-and-miss affair, and it takes time to form the right structure. Hence, the reaction has a delay time, after deoxygenation, that is shortened by an increase in intracellular hemoglobin concentration (above the normal 33 g/dl), by lowering the pH and by increasing the temperature. This explains why red cell dehydration and infections are serious in sickle cell anemia patients. The final products of polymerization are double-stranded fibers which lead to red cell deformity with protuberances (Figure 14.6).
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