Sickle Cell Disease

Abstract

1. M. Catherine Driscoll, MD* 1. *Director, Hematology Program, Children's Hospital at Montefiore, Bronx, NY After completing this article, readers should be able to: 1. Describe the pathogenesis of sickle cell disease. 2. Delineate the complications of sickle cell disease and their management. 3. Review guidelines for health maintenance and preventive measures. 4. Discuss the current treatments for sickle cell disease. Sickle cell disease (SCD) is a chronic hemolytic anemia that includes the hemoglobin (Hb) variants SS, SC, S-beta thalassemia, SO Arab, SD, and other rare S-Hb genotypes. SCD is one of the most common genetic diseases worldwide. Sickle disorders are seen commonly in sub-Saharan Africa but also occur in the Mediterranean, India, and the Arabian Peninsula. The geographic distribution of sickle hemoglobinopathies corresponds to the distribution of malaria; indeed, the sickle gene in the heterozygote (AS) form protects against death from endemic Plasmodium falciparum malaria infection. In addition, the clinical manifestations of SCD vary among these geographic sites, with individuals from India, the Arabian Peninsula, and Senegal having milder disease than those from parts of Africa. This pattern suggests that genetic modifiers ameliorate the disease in certain populations and contribute to the significant variation in clinical manifestations. The presence of SCD in North, South, and Central America is due to immigration patterns and represents primarily the more severe African types. The genetic defect producing sickle Hb is a single nucleotide substitution (GTG for GAG) at codon 6 of the beta globin gene on chromosome 11 that results in the substitution of valine for glutamic acid. This hydrophobic amino acid substitution allows Hb S to polymerize on deoxygenation, and multiple polymers bundle to form rodlike structures that distort the red cell into the classic crescent shape. Sickled red cells are less deformable in the microcirculation and provoke a cascade of events that results in vascular occlusion, organ ischemia, and eventually, chronic end-organ damage. The ancillary events of polymerization that …