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Increased levels of 2,3-Diphosphoglycerate (2,3-DPG) are associated with the risk factors for hemoglobin S (HbS) polymerization, particularly in the context of sickle cell disease. 2,3-DPG plays a critical role in the regulation of hemoglobin’s affinity for oxygen. When 2,3-DPG levels are elevated, it promotes the release of oxygen from hemoglobin, facilitating the delivery of oxygen to tissues. However, in individuals with sickle cell disease, high concentrations of 2,3-DPG can lead to a situation where the deoxygenated form of hemoglobin S is more likely to polymerize, contributing to the sickling of red blood cells.

When hemoglobin S is deoxygenated, it tends to aggregate and form long, rigid polymers that distort red blood cell shape into a sickle form, leading to vaso-occlusive episodes and other complications. Therefore, the presence of elevated 2,3-DPG is significant in this process, as it can aggravate the polymerization of HbS under low oxygen conditions.

Other compounds mentioned, such as ATP, cAMP, and GTP, do not have a direct role in the polymer