Sickle Cell Anemia

Sickle Cell Anemia

Sickle cell anemia is an inherited blood disorder, characterized primarily by chronic anemia and periodic episodes of pain. The underlying problem involves hemoglobin, a component of the red cells in the blood. The hemoglobin molecules in each red blood cell carry oxygen from the lungs to the body organs and tissues and bring back carbon dioxide to the lungs. In sickle cell anemia, the hemoglobin is defective. After the hemoglobin molecules give up their oxygen, some of them may cluster together and form long, rod-like structures. These structures cause the red blood cells to become stiff and to assume a sickle shape. Unlike normal red cells, which are usually smooth and donut-shaped, the sickled red cells cannot squeeze through small blood vessels. Instead, they stack up and cause blockages that deprive the organs and tissue of oxygen-carrying blood. This process produces the periodic episodes of pain and ultimately can damage the tissues and vital organs and lead to other serious medical problems. Unlike normal red blood cells, which last about 120 days in the bloodstream, sickled red cells die after only about 10 to 20 days. Because they cannot be replaced fast enough, the blood is chronically short of red blood cells, a condition called anemia.

In the western literature, the first description of sickle cell disease was by a Chicago physician, James B. Herrick, who noted in 1910 that a patient of his from the West Indies had an anemia characterized by unusual red cells that were "sickle-shaped". In 1927, Hahn and Gillespie showed that sickling of the red cells was related to low oxygen. In 1940, Sherman (a student at Johns Hopkins Medical School) noted a birefringence of deoxygenated red cells, suggesting that low oxygen altered the structure of the hemoglobin in the molecule. Janet Watson, a pediatric hematologist in New York, suggested in 1948 that the paucity of sickle cells in the peripheral blood of newborns was due to the presence of fetal hemoglobin in the red cells, which consequently did not have the abnormal sickle hemoglobin seen in adults. Using the new technique of protein electrophoresis, Linus Pauling and Harvey Itano showed in 1948 that the hemoglobin from patients with sickle cell disease is different than that of normal people. This made sickle cell disease the first disorder in which an abnormality in a protein was known to be at fault. In 1956, Vernon Ingram, then at the MRC in England, and J.A. Hunt sequenced sickle hemoglobin and showed that a