The sickling process progresses through stages of nucleation, growth, and alignment.
Nucleation involves the aggregation of a small number of hemoglobin tetramers into clusters or short linear polymers. This stage is also called the lag phase. These clusters may be reversed upon re-oxygenation.
With each repeated occurrence, the polymers continue to grow. In this polymerization stage, the internal cellular viscosity increases.
Eventually the fibers that are formed become irreversible crystalline structures, which align into bundles, thus creating the pointed elongated and typically crescent-shaped morphologies associated with sickle cells (drepanocytes) as seen in the peripheral blood field below.
