Whats New in the Pathophysiology of Sickle Cell Disease?

Hemoglobin S (Hb S) is the most widely distributed structural hemoglobin (Hb) variant and results from the substitution of valine for glutamic acid in the 6th amino acid in the β-globin chain. This leads to reduced solubility of the Hb molecule especially in a deoxygenated medium with the formation of polymers, which distort the red blood cell (RBC) membrane causing rigidity and less deformability of the cell. In addition, there is reduced life span of the RBC. Homozygotes or compound heterozygotes (Sβ0thal, SC, etc.) have sickle cell disease (SCD), which is characterized by recurrent vaso-occlusion with consequent body pains, chronic hemolysis and end-organ damage.