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:
COMPLICATIONS
1. Increased risk of bacterial infection, primarily due to hypofunctional spleen: overwhelming sepsis, meningitis (children with sickle cell anemia have 36 times greater incidence of pneumococcal meningitis), pneumococcal pneumonia, Salmonella osteomyelitis
2. Reproductive and sexuality: delayed onset of puberty, impaired fertility, priapism
3. Gastrointestinal: gallstones
4. Respiratory: “acute chest syndrome”—respiratory distress with cough and tachypnea, high fever, chest pain, and infiltrate on chest radiographic studies
5. Cardiovascular: chronic heart, liver, and kidney disease, CVAs (10%, especially between ages of 3 and 10 years), avascular necrosis, leg ulcers, proliferative retinopathy
7. Psychiatric and psychosocial: depression, isolation, low self-esteem, risk for drug addiction (actual prevalence in this population is low, according to recent literature), strained parent-child relationships
LABORATORY AND DIAGNOSTIC TESTS
Refer to Appendix D for normal values and ranges of laboratory and diagnostic tests.
1. Hemoglobin electrophoresis, preferably at birth for all infants as part of newborn screening—to quantify percentage of hemoglobin S present. If disorder is not identified at birth, diagnosis is rarely made before 6 to 12 months of age.
2. Tests of fetal blood or fetal cells—to make prenatal diagnosis possible between 9 and 11 weeks’ gestation.
MEDICAL MANAGEMENT
Medical management focuses on pain control, oxygenation, hydration, and careful monitoring for complications of vasoocclusion. Administration of prophylactic penicillin to prevent septicemia should be initiated at 2 to 3 months of age and continued through 5 to 6 years of life. Immunizations are crucial to protect these children from infection. Specifically required are (1) pneumococcal conjugate vaccine (PCV7), four doses between 2 months and 2 years of age; (2) pneumococcal polysaccharide vaccine (PPV23) starting at 2 years of age; and (3) influenza vaccine every fall for children over 6 months of age. Meningococcal vaccine is sometimes recommended for asplenic children.
Transcranial Doppler ultrasonography is being used in some centers to identify children who are at high risk for developing a first stroke. Subsequent initiation of a long-term transfusion program for those with abnormal test results may decrease the incidence of stroke.
A program of hypertransfusion (transfusion every 3 to 4 weeks) is a current treatment (90% effective) for children who have had CVAs, progressive pulmonary disease, and possibly debilitating vasoocclusive crisis. The iron overload leads to hemosiderosis (iron deposits on organs), with the following complications occurring: cardiomyopathy, cirrhosis, insulin-dependent diabetes mellitus, hypothyroidism, hypoparathyroidism, delayed growth, and delayed sexual development. Deferoxamine (Desferal), administered either subcutaneously or by intravenous transfusion at regular intervals, will chelate the iron so that it can be excreted through the urine or bile to help reduce these complications.
Analgesics are used to control pain during a crisis period. Antibiotics may be used, because infection can trigger the crisis. Folic acid supplementation may be considered for children with significant hemolysis. Daily administration of oral hydroxyurea in adults 18 years and older is an effective pharmacologic intervention, although use in children has not been well studied. Treatment with hydroxyurea, which increases levels of fetal hemoglobin, has been shown to reduce pain events, hospital admissions, and the need for blood transfusions.
The only cure is thought to be a bone marrow transplant, which also involves risks. This may be a promising treatment modality in the near future.
NURSING ASSESSMENT
See the Cardiovascular Assessment and Respiratory Assessment sections in Appendix A and the Pain Assessment section in Appendix I.
NURSING INTERVENTIONS
1. Prevent or minimize effects of sickle cell crisis.
2. Provide frequent rest periods to decrease oxygen expenditure.
3. Monitor use of oxygen equipment.
4. Administer and monitor use of blood products and chelation therapy; assess for signs of transfusion reaction—fever, restlessness, cardiac arrhythmias, chills and shaking, nausea and vomiting, chest pain, red or black urine, headache, flank pain, and signs of shock or renal failure.
5. Monitor for signs of circulatory overload—dyspnea, increased respiratory rate, cyanosis, chest pain, and dry cough.
6. Relieve or minimize pain (see Appendix I).
8. Monitor for signs of complications.
9. Provide age-appropriate explanation to child about hospitalization and procedures (see Appendix B).
10. Ensure good nutrition. Metabolic rate of children with sickle cell disease has been demonstrated to be higher than that of children without the disease.
11. Provide emotional support to child and family (see the Supportive Care section in Appendix F).
12. Encourage parents to screen their family members.
13. Identification at birth makes possible early prophylaxis against infections. Use of prophylactic penicillin is recommended beginning in newborn period (2 to 3 months of age).
Discharge Planning and Home Care
1. Provide genetic counseling.
2. Counsel child on appropriate play, leisure activities, and sports participation (to prevent hypoxia resulting from strenuous physical exertion and excessive life stress).
3. Provide parent teaching and anticipatory guidance about prevention of infection to ensure that child is seen by physician at first signs of illness; teach parents procedure for taking temperature and methods to decrease temperature.
4. Counsel parents on the importance of encouraging the child’s self-reliance as appropriate for age.
5. Provide parents with information about routine immunizations. Child should have annual vision screening.
CLIENT OUTCOMES
1. Child’s respiratory rate, oxygen saturation, and arterial blood gas levels will be within normal limits, cyanosis will be absent, and urine output will be higher than 1 ml/kg/hr.
2. Child will indicate relief from pain.
3. Child and family will understand importance of medical follow-up and know when to seek medical attention.
4. Child will have minimal vasoocclusive, sequestration, and aplastic crises.
5. Child will demonstrate regular observable growth and achieve age-appropriate developmental milestones (see Appendix B).
6. Family will seek genetic counseling for other children.
7. Parents will be able to accurately describe disease process and identify special precautions necessary to prevent sickle cell crisis (Box 71-2).
Box 71-2 Resources
• The Sickle Cell Information Center: www.SCInfo.org (404-616-3572)
• The Sickle Cell Disease Association of America: www.sicklecelldisease.org (800-421-8453)
• The Sickle Cell Disease Scientific Research Group: NHLBI Health Information Center: www.nhlbi.nih.gov (301-592-8573 or 240-629-3255 TTY)
American Academy of Pediatrics. Health supervision for children with sickle cell disease, policy statement, American Academy of Pediatrics Web Site. (serial online): http://aappolicy.aappublications.org/cgi/reprint/pediatrics;109/3/526.pdf, 2006. Accessed May 6, 2006
Learn about sickle cell disease and sickle cell trait, 2004 edition (08–04-A), Channing Bete Company, pamphlet number PS21828
The Sickle Cell Information Center. Sickle Cell information—Clinician summary, The Sickle Cell Information Center. (serial online): www.scinfo.org/prod05.htm, 2006. Accessed May 6, 2006
