Management of Sickle Cell Disease

Description: Sickle cell disease (SCD) results from the substitution of a valine residue for glutamic acid at position 6 in the beta-subunit of hemoglobin (Ingram, 1956). With a few minor exceptions, people with only one gene for hemoglobin S (Hb S) are phenotypically normal (sickle trait). People who inherit two Hb S genes from their parents have sickle cell disease. Deoxygenated Hb S tends to polymerize non-covalently into long strands that deform the erythrocyte, giving the characteristic "sickle cell" morphology (Eaton and Hofrichter, 1990). Hb S with bound oxygen (e.g., in the arterial circulation) does not polymerize. The mechanism by which these changes in the physical properties of the hemoglobin molecule produce the clinical manifestations of the disease is not unequivocally proven. The most widely accepted hypothesis is that erythrocytes deform as they release their oxygen in the capillaries and are trapped in the microcirculation (Eaton et al., 1976) (Kaul et al., 1989). The blockade of blood flow produces areas of tissue ischemia, leading to the myriad of clinical problems seen with sickle cell disease. Although a good deal of indirect evidence supports this theory, definitive proof that this is the pathophysiologic mechanism in sickle cell disease is lacking.