Sickle Cell Anemia
A congenital hemolytic disease, sickle cell anemia results from a defective hemoglobin molecule (hemoglobin S) that causes red blood cells (RBCs) to become sickle shaped. Such cells impair circulation, resulting in chronic ill health (fatigue, dyspnea on exertion, and 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 African Americans carries the abnormal gene. If two such carriers have offspring, each child has a 1in 4 chance of developing 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 area. Possibly, the defective hemoglobin S-producing gene has persisted because in areas where malaria is endemic, the heterozygous sickle cell trait provides resistance to malaria and is actually beneficial.
Penicillin prophylaxis can decrease morbidity and mortality from bacterial infections.
Causes
Sickle cell anemia results from homozygous inheritance of the hemoglobin S-producing gene, which causes substitution of the amino acid valine for glutamic acid in the beta hemoglobin chain. Heterozygous inheritance of this gene results in sickle cell trait, a condition with minimal or no symptoms. The patient with sickle cell trait is a carrier; he can pass the sickle cell gene to his offspring.
In sickle cell anemia, the abnormal hemoglobin S found in the patient’s RBCs 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).
Each person with sickle cell anemia has a different hypoxic threshold and different factors that precipitate a sickle cell crisis. Illness, cold exposure, and stress are known to precipitate sickling crises in most people.
In addition, these altered cells accumulate 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.
Complications
Sickle cell anemia causes long-term complications. An adult with this disease may develop chronic obstructive pulmonary disease, heart failure, or organ infarction, such as retinopathy and nephropathy. Splenic infarctions are common and often cause significant necrosis early in life, so that splenomegaly leads to a small, nodular, and malfunctioning spleen. Infection or repeated occlusion of small blood vessels and consequent infarction or necrosis of major organs commonly cause premature death. For example, cerebral blood vessel occlusion causes cerebrovascular accident and is the most common cause of death in severe sickle cell disease. Frequent sickling and hyperviscosity can lead to heart murmurs and heart failure.
Assessment
Signs and symptoms usually don’t develop until after age 6 months, because large amounts of fetal hemoglobin protect infants for the first few months after birth.
Characteristically, the patient history in sickle cell anemia includes chronic fatigue, unexplained dyspnea or dyspnea on exertion, joint swelling, aching bones, chest pain, ischemic leg ulcers (especially around the ankles), and an increased susceptibility to infection. The patient’s medical history may include pulmonary infarctions and cardiomegaly. Inspection of an adult usually reveals a spiderlike body build (narrow shoulders and hips, long extremities, curved spine, and barrel chest).
Pediatric pointerInspection for sickle cell anemia in children may reveal jaundice or pallor. A young child may appear small for his age, whereas an older child may experience delayed growth and puberty.
Differentiating types of sickle cell crisis
The following characteristic signs and symptoms help determine the type of sickle cell crisis the patient is experiencing.
Vaso-occlusive crisis
The most common crisis and the hallmark of this disease, a vaso-occlusive crisis (painful crisis, infarctive crisis) usually appears periodically after age 5. It results from blood vessel obstruction by rigid, tangled sickle cells, which causes tissue anoxia and, possibly, necrosis.
Vaso-occlusive crisis is characterized by severe abdominal, thoracic, muscle, or bone pain and, possibly, increased jaundice, dark urine, or a low-grade fever. Patients with long term disease may experience autosplenectomy, in which splenic damage and scarring is so extensive that the spleen shrinks and becomes impalpable. This can lead to increased susceptibility to Streptococcus pneumoniae sepsis, which can be fatal without prompt treatment. After the crisis subsides (in 4 days to several weeks), infection may develop, producing lethargy, sleepiness, fever, and apathy.
Aplastic crisis
Associated with infection (usually viral), an aplastic crisis (megaloblastic crisis) results from bone marrow depression. It’s characterized by pallor, lethargy, sleepiness, dyspnea, possible coma, markedly decreased bone marrow activity, and red blood cell (RBC) hemolysis.
Acute sequestration crisis
Occurring in infants between ages 8 months and 2 years, an acute sequestration crisis may cause sudden, massive entrapment of RBCs in the spleen and liver. This rare crisis causes lethargy and pallor and, if untreated, commonly progresses to hypovolemic shock and death.
