Sickle cell anemia
A congenital hemolytic anemia that occurs primarily, but not exclusively, in blacks, sickle cell anemia results from a defective hemoglobin (Hb) molecule (Hb S) that causes red blood cells (RBCs) to roughen and become sickle shaped. Such cells impair circulation, resulting in chronic ill health (fatigue, dyspnea on exertion, swollen joints), periodic crises, long-term complications, and premature death.
Sickle cell anemia is most common in tropical Africans and in people of African descent; about 1 in 10 blacks carries the abnormal gene. If two such carriers have offspring, there is a 1 in 4 (25%) chance that each child will have the disease. Overall, 1 in every 400 to 600 black children has sickle cell anemia.
This disease also occurs in Puerto Rico, Turkey, India, the Middle East, and the Mediterranean, as well as in other populations. The defective Hb gene may have persisted in areas where malaria is endemic because the hetero-zygous sickle cell trait provides resistance to malaria and is actually beneficial.
Penicillin prophylaxis can decrease morbidity and mortality from bacterial infections. Half of such patients die by their early twenties; few live to middle age.
Causes
Sickle cell anemia results from homo-zygous inheritance of the Hb S gene, which causes substitution of the amino acid valine for glutamic acid in the B Hb chain. Heterozygous inheritance of this gene results in sickle cell trait, usually an asymptomatic condition. (See Sickle cell trait, page 774.)
Altered cells
The abnormal Hb S found in RBCs of patients with sickle cell anemia becomes insoluble whenever hypoxia occurs. As a result, these RBCs become rigid, rough, and elongated, forming a crescent, or sickle, shape. Such sickling can produce hemolysis (cell destruction).
In addition, these altered cells tend to pile up in capillaries and smaller blood vessels, making the blood more
viscous. Normal circulation is impaired, causing pain, tissue infarctions, and swelling. Such blockage causes anoxic changes that lead to further sickling and obstruction.
viscous. Normal circulation is impaired, causing pain, tissue infarctions, and swelling. Such blockage causes anoxic changes that lead to further sickling and obstruction.
Sickle cell trait
This relatively benign condition results from heterozygous inheritance of the abnormal hemoglobin S (Hb S) gene from one parent, while receiving one normal Hb gene from the other parent. Like sickle cell anemia, this condition is most common in blacks. Sickle cell trait never progresses to sickle cell anemia.
In persons with sickle cell trait (also called carriers), 20% to 40% of their total Hb is Hb S; the rest is normal.
Such carriers usually have no symptoms. They have normal Hb and hematocrit values and can expect a normal life span. Nevertheless, they must avoid situations that provoke hypoxia because these occasionally cause a sickling crisis similar to that in sickle cell anemia.
Genetic counseling is essential for sickle cell carriers. If two sickle cell carriers marry, each of their children has a 25% chance of inheriting sickle cell anemia.
Signs and symptoms
Characteristically, sickle cell anemia produces tachycardia, cardiomegaly, systolic and diastolic murmurs, pulmonary infarctions (which may result in cor pulmonale), chronic fatigue, unexplained dyspnea or dyspnea on exertion, hepatomegaly, jaundice, pallor, joint swelling, aching bones, chest pains, ischemic leg ulcers (especially around the ankles), and increased susceptibility to infection.
Such symptoms usually don’t develop until after age 6 months, because large amounts of fetal Hb protect infants for the first few months after birth. Low socioeconomic status and related problems, such as poor nutrition and education, may delay diagnosis and supportive treatment.
Infection, stress, dehydration, and conditions that provoke hypoxia— strenuous exercise, high altitude, unpressurized aircraft, cold, and vasoconstrictive drugs—may all provoke periodic crisis. Four types of crises can occur: painful, aplastic, acute sequestration, or hemolytic.
Painful crisis
Also called a vaso-occlusive crisis or infarctive crisis, painful crisis is the most common crisis and the hallmark of this disease. It usually appears periodically after age 5.
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