Adhesion molecules and hydroxyurea in the pathophysiology of sickle cell disease

ickle cell disease (SCD) is a systemic disorder caused by a mutation in the gene encoding the chain of hemoglobin. This mutation leads to the production of sickle hemoglobin (HbS) which is predisposed to polymerization while the hemoglobin is not oxygenated. HbS polymerization and Hb denaturation are thought to result in oxidant damage to the red blood cell membrane. Associated with such damage is abnormal erythrocyte cation homeostasis, which in turn can result in dehydrated dense cells and irreversibly sickled cells. 1 Red cell abnormalities result in both hemolysis and vaso-occlusion. Vaso-occlusion appears to be a complex event mediated by red cell and leukocyte adhesion, inflammation, injury to the endothelium, and activation of coagulation pathways. In addition, hemolysis probably contributes to dysregulation of nitric oxide. Vasoocclusion is the major cause of morbidity and mortality in SCD, with occlusion of blood vessels followed by ischemia or infarction in various tissues, leading ultimately to progressive end organ damage.