Fig. 5.

Intracellular concentration distributions and fraction sickled at equilibrium in SS disease, S/HPFH, and sickle trait (AS). The ordinate is the probability of a red cell containing a total hemoglobin concentration (c) indicated on the abscissa. The dark red area shows cells where the solution in the cell is supersaturated at 75% saturation with oxygen of the free hemoglobin molecules (i.e., the initial Hb concentration is greater than the equilibrium solubility), while the light red area shows the cells that are superstaurated at 50% saturation (p50) with oxygen of the free hemoglobin. See (Henry et al., 2020a) for details of the concentration distributions and sickling calculations, which also include the large non-ideality from molecular crowding in these concentrated protein soluitons, as well as copolymerization of HbF in SS disease (~90% HbS, ~10% HbF) and in S/HPFH (~70% HbS, ~30% HbF), and HbA in sickle trait (~40% HbS, ~60% HbA).(Eaton and Hofrichter, 1990; Ross and Minton, 1977). The larger portion of cells at lower and higher hemoglobin concentrations in SS disease compared to S/HPFH and sickle trait correspond to an increase in reticulocyte production responding to the anemia and dehydration from mutiple sickling/unsickling cycles. respectively.