Sickle-cell anemia results from the inheritance of the gene for S hemoglobin from each parent. In the United States, 1 of 12 African-Americans has sickle-cell trait, which results from inheritance of one gene for hemoglobin S and one for normal hemoglobin A. he computed incidence of sickle-cell anemia among frican-Americans is 1 in 576 (1112 X 1112 X 114 = 11576). But, the disease is less common in adults because of earlier mortality. Hemoglobin C originates from a single 3-chain substitution of glutamic acid by lysine, which stems from a T -forC substitution at codon 6 of the 3-globin gene. Approximately 1 in 40 African-Americans has the gene for hemoglobin C. Thus, the theoretical incidence for co inheritance of the gene for hemoglobin S and an allelic gene for hemoglobin C in an frican-American child is about 1 in 2000 (1/12 X 1140 X 114). 3-halassemia minor is approximately 1 in 40, thus S-3-thalassemia also is found in approximately 1 in 2000 (1/12 X 1140 X 114).
Red cells with hemoglobin S undergo sickling when they are deoxygenated, and the hemoglobin aggregates. Constant sickling and unsickling cause membrane damage, and the cell may become irreversibly sickled. Events that slow erythrocyte transit through the microcirculation include adhesion to endothelial cells, erythrocytic dehydration, and vasomotor dysregulation. Clinically, the hallmarks of sickling episodes are periods during which there is ischemia and infarction in various organs. The sickle-cell crisis produces clinical symptoms, predominately pain, which is often severe. There may be aplastic, megaloblastic, sequestration, and hemolytic crises.
Chronic and acute changes from sickling include bony abnormalities such as osteonecrosis of femoral and humeral heads, renal medullary damage, autosplenectomy in homozygous SS patients and splenomegaly in other variants, hepatomegaly, ventricular hypertrophy, pulmonary infarctions, pulmonary hypertension, cerebrovascular accidents, leg ulcers, and a propensity for infection and sepsis (Benz, 2015; Gladwin, 2004). Other sequelae are cerebrovascular aneurysms and sickle-cell vasculopathy (Buonanno, 2016). Pulmonary hypertension can develop and is found in 20 percent of adults with SS hemoglobin (Gladwin, 2008).
Good supportive care is essential to prevent mortality. Speciic therapies are evolving, and many are still experimental. One treatment is hemoglobin F induction with drugs that stimulate gamma-chain synthesis. This increases hemoglobin F, which inhibits hemoglobin S polymerization. One example is hydroyurea, which augments hemoglobin F production and reduces the number of sickling episodes (Platt, 2008). Hydroxyurea is teratogenic in animls, although a preliminary 17 -year surveillance of antenatally exposed children was reassuring (Ballas, 2009; Briggs, 2015; Italia, 2010). A randomized trial showed no benefit from treatment with prasurel, a platelet inhibitor (Henney, 2016). Treatment with crianlizumab, an antibody against P-selectin, signiicantly lowered the incidence of adverse events (Ataga, 2017).