Pathophysiology of sickle cell disease (SCD)
Hemolysis, vasoocclusion, and ischemia reperfusion are the clinical hallmarks of SCD. The substitution of glutamate for valine at position 6 of the hemoglobin β-chain is the mutation defining hemoglobin S (HbS).
HbS polymerizes when the concentration of its deoxygenated form exceeds a critical threshold. Conditions that promote HbS polymerization and red blood cell sickling include low local oxygen tension, acidemia (reduces HbS affinity for oxygen), and hyperosmolality (dehydrates red blood cells and increases HbS concentration).
Extensive HbS polymerization, red blood cell sickling, cell membrane injury, and associated cell membrane adhesive interactions with the endothelium contribute to vasoocclusion leading to multiorgan damage.