Chapter 71 Sickle Cell Disease
PATHOPHYSIOLOGY
Sickle cell disease is a general term that is used to describe a group of related disorders that affect the red blood cells. The basic defect is a mutant autosomal gene that effects a substitution of valine for glutamic acid on the beta chain of hemoglobin. The result is a person with either a heterozygous or homozygous hemoglobinopathy. A person diagnosed with sickle cell trait (heterozygous form Hb AS) has inherited the sickle gene from only one parent and will not have any signs and symptoms of sickle cell disease. Sickle cell trait cannot change into sickle cell disease; however, there is a 50% chance that affected persons will pass the trait to their offspring. Sickle cell anemia, or homozygous sickle cell disease (Hb SS), is an inherited autosomal recessive disorder, which means that a person has inherited the sickle gene from both parents and will have signs and symptoms of disease. There are other variants of sickle cell anemia as well; Hb SC, Hb SB thalassemia, Hb SD, and Hb SE are the most common. Sickled red blood cells are crescent-shaped, have decreased oxygen-carrying capacity, and undergo destruction at a greater rate than normal red blood cells. The life span of sickled cells is diminished to 10 to 30 days (normal is 120 days). Sickled cells are extremely rigid because of the gelled hemoglobin, cellular dehydration, and an inflexible membrane. The rigid cells become trapped in the circulatory system, which leads to a vicious cycle of infarction and progressive sickling.
Splenic hypofunction and, later, splenic atrophy result in reticuloendothelial failure and an incidence of infection that is 600 times higher in children with sickle cell disease than in the normal population. Children are born with fetal hemoglobin, which consists of a gamma chain; therefore, until approximately 6 months of age, when the hemoglobin begins to change to the adult type, symptoms of the disease do not usually occur (Box 71-1).
Box 71-1 Early Detection: Newborn Screening Programs
• Morbidity and mortality can be significantly reduced with newborn screening and early intervention.
• Screening should include prenatal, maternal, and neonatal screening.
• Public education is critical for effective neonatal screening. Target groups include day care centers, schools, and the media.
Adapted from Commission on Classification and Terminology of the International League Against Epilepsy: Proposal for revised clinical and electroencephalographic classification of epileptic seizures, Epilepsia 22(4): 489, 1981, currently under revision.In: Dreifuss FE: Classification of the epilepsies: Influence on management. In: Santilli N, editor: Managing seizure disorders: A handbook for health care professionals,Philidelphia, 1998, Lippincott-Raven.
Sickle cell crises result from physiologic changes that decrease the oxygen available to the hemoglobin; they are typically precipitated by dehydration, infection, and hypoxia. Sickling of cells results in clumping of red blood cells in the vessels, decreased oxygen transport, and increased destruction of red blood cells. Ischemia, infarct, and tissue necrosis result from the obstruction of vessels and decreased blood flow. Three types of crisis occur: (1) vasoocclusive (painful), (2) splenic sequestration, and (3) aplastic. Sickle cell crises occur less frequently with age. Mortality in the first years of life is usually caused by infection and sequestration crisis.
INCIDENCE
1. Incidence of sickle cell trait among African Americans is estimated at 1 in 12, and incidence of sickle cell disease is estimated at 1 in 375. The disease has also been reported occasionally in those from certain areas of the Mediterranean basin (Turkey, Greece, Italy), the Caribbean, and South and Central America, as well as in some with Arabian, Asiatic Indian, Native American, or East Indian ancestry.
2. Approximately 2000 infants are born with sickle cell disease each year in the United States.
3. Death occurs most frequently in children from 1 to 3 years of age from organ failure or thrombosis of major organs, most commonly the lungs and the brain.
4. With new treatments, 85% of affected individuals survive to the age of 20 years; 50% survive beyond 50 years.
CLINICAL MANIFESTATIONS
1. Vasoocclusive crisis (painful crisis) results from ischemia in tissue distal to occlusion. Crises can occur when the child has an illness that causes dehydration or a respiratory infection that lowers oxygen exchange. Other precipitating events can be exposure to cold, anesthesia, or high altitudes, or extremely strenuous exercise. Fifty percent of children will have a vasoocclusive crisis by 1 year of age, and close to 100% will suffer from one by the age of 6 years. Vasoocclusive crisis is characterized by the following symptoms:
2. Sequestration crisis (usually seen in children from 5 to 36 months of age, with 76% of cases occurring before age 2 years) is due to the sequestration of sickled blood within the spleen over a period of hours, which rapidly decreases the hemoglobin level (blood pooled in the spleen is not available to the general circulation). Children are subject to fatal splenic rupture and/or splenic atrophy. Signs and symptoms of sequestration crisis are as follows:
3. Aplastic crisis results from a transient suppression of red cell production while hemolysis continues at the same rate. It often occurs in association with an infection, when the strong compensatory mechanism is depressed (e.g., parvovirus B19, Salmonella, Streptococcus, Mycoplasma, Epstein-Barr virus infections). Aplastic crisis typically occurs in children younger than 10 years. Signs and symptoms of aplastic crisis are as follows:
