How do red blood cells (RBCs) sickle in sickle cell anemia?

In sickle cell anemia, red blood cells (RBCs) undergo a transformation into a sickle or crescent shape due to the presence of sickle hemoglobin (HbS). When oxygen levels are low or there is increased dehydration, these cells can lose their normal biconcave disk shape. The correct understanding here is that the RBCs can become irreversibly sickled after multiple episodes of deoxygenation and stress. This transformation is a critical feature of the disease and leads to various complications, including vaso-occlusive crises, where the sickled cells clump together and obstruct blood flow, ultimately resulting in pain and potential organ damage.

While hydration can help improve the shape of sickled cells temporarily, the characteristic nature of sickle cell anemia is that once RBCs sickle under certain conditions, they can become irreversibly sickled, leading to chronic complications associated with the disease. This irreversible sickling is a key factor that distinguishes sickle cell anemia from other conditions affecting red blood cell shape or function.