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Sickle Cell Anemia - Prevention NEWBORN SCREENING Newborn screening for sickle cell disease is an effective first step to reduce morbidity and mortality in individuals with the disease. Parents of newborns with a positive screening test result for sickle cell disease must be contacted before the child becomes 2 months of age to confirm the diagnosis. The diagnosis should be confirmed by a laboratory with expertise in analysis of variant hemoglobins. If a child who is presumed to have sickle cell disease through newborn screening is not retested by 4 months of age, he or she should be started on penicillin VK (125 mg given orally twice a day) pending confirmation; the medication can be discontinued in the rare instance that the hemoglobin screening test result was erroneous or is found to represent a benign disorder. Once the disease diagnosis is confirmed, the infant must receive care in an ongoing and comprehensive medical program that includes oral penicillin given twice a day for the prevention of overwhelming Streptococcus pneumoniae infection and parent education about sickle cell disease. The medical program should be staffed by health care professionals who are sensitive to the special needs of infants with sickle cell syndromes and are aware of their propensity to lifethreatening infection and death from complications such as acute splenic sequestration and acute chest syndrome.All infants, of every ethnic group, should be tested to ensure the identification of all affected newborns. Where possible, sickle cell disease screening should be coupled with other newborn screening tests performed to detect hypothyroidism and inborn errors of metabolism. Several screening methodologies are acceptable, including hemoglobin electrophoresis on cellulose acetate and citrate agar, isoelectric focusing, and highpressure liquid chromatography. Because of the high concentration of Hb F in newborns, solubility tests or sickle cell preparations (sodium metabisulfite) should not be used to confirm the presence of Hb S until the infant has reached 12 months of age and should never be used as a sole diagnostic laboratory procedure. States that test for sickle cell disorders as part of their newborn screening procedures usually confirm the original test result by retesting the child and will also request a repeat specimen if the history indicates that the child was transfused before the blood sample was obtained. It must be emphasized that the responsibility for a final and definitive diagnosis rests with the child’s physician. Red cells of normal newborns contain hemoglobins F and A, “FA,” the hemoglobin in highest concentration being listed first. The hemoglobin pattern or phenotype is due to predominance of Hb F at birth. Newborns with sickle cell trait have an “FAS” phenotype, with more Hb A than Hb S. Infants with SC disease have an “FSC” pattern, those with SS disease, Sb o thal, and S HPFH each have an “FS” phenotype on newborn screening. Although infants with Sb + thal will generally have an “FSA” pattern on screening, the percentage of Hb A may be so small that these infants will also have an “FS” phenotype. Definitive diagnosis may require testing both parents or deoxyribonucleic acid (DNA) typing of the infant or retesting the infant after 9 months. It is important to remember that newborns with “FA” patterns are not necessarily hematologically normal—they do not have sickle cell disease but may have thalassemia or another disorder of red blood cells. When definitive diagnostic tests cannot be performed in early infancy, it is best to assume that the infant has SS disease, the most common of the FS disorders. When infants are doubly heterozygous for sickle cell and another abnormal hemoglobin other than C, definitive identification by a knowledgeable hematologist is necessary. In addition to identifying the affected newborn, newborn screening also provides an opportunity to identify couples at risk for having children with sickle cell disorders. Parents of newborns identified with sickle cell trait or hemoglobin C trait should be offered testing for all hemoglobinopathies, including thalassemia, and be appropriately counseled. Newborn screening may identify variant hemoglobins other than S or C. When these are coinherited with Hb S, a definitive diagnosis must be made. Hemoglobin S o Arab disease, for instance, is as serious a condition as SS disease, while the combination of Hb S and Baltimore is as benign as sickle cell trait. If the child has only Hb A and the variant, further diagnostic tests are usually unnecessary, if the child is hematologically normal in other aspects. PREVENTION Immunization Children with SS disease have a normal antibody response to vaccines and should receive all immunizations recommended by the American Academy of Pediatrics (these change periodically, and the most current recommendations should be followed (see Table 2)). In addition, children should receive pneumococcal vaccine. Some clinicians recommend that the influenza vaccine be administered according to epidemiologic considerations.Antibiotic Prophylaxis Prophylactic penicillin is so effective in reducing the number of lifethreatening episodes of pneumococcal sepsis in children with SS disease under age 5 years that most States screen newborns for the disease so they can be placed on the drug by 2 to 3 months of age. Oral penicillin VK (125 mg given twice a day up to age 3 years, then 250 mg given twice a day) is the preferred form of treatment. Prophylaxis should be given to children with SS disease and Sb o thal starting at 2 to 3 months of age and continuing until at least age 5 years. Prophylaxis in older children has not been shown to be beneficial and may be unnecessary after pneumococcal immunizations are complete and antibody titers are protective. Some clinicians give prophylaxis to children with SC disease or Sb + thal: there is an increased risk of severe infection in such patients, although it is less than in SS disease or Sb o thal. Compliance with penicillin prophylaxis can be achieved, provided that a dedicated team of physicians, nurses, and health care educators engage families in intensive educational programs.
Neither the pneumococcal vaccine nor
available antibiotics has been shown to
eliminate nasopharyngeal colonization with
S. pneumoniae, Neisseria meningitis, and
H. influenzae in normal young children orthose with sickle cell disease. Prophylactic
antibiotics prevent bacteremia and tissue
invasion, despite continued nasopharyngeal
carriage or reexposure. When failure
occurs, it may be due to a variety of microbiologic
causes as well as a lack of patient
compliance. As discussed below, the emergence
of penicillin and cephalosporinresistant
S. pneumoniae is a serious evolving
problem in many communities and
may ultimately undermine the effectiveness
of the established prophylactic regimen.
Clinicians should be aware that recommendations
concerning the use of prophylactic
penicillin and the choice of empiric antibiotics
in patients with sickle cell disease
may well undergo tremendous change during
the next few years. At present, the
most effective approach is a combination
of traditional pneumococcal vaccination
and regular penicillin prophylaxis; it is
hoped that newer conjugated pneumococcal
vaccines will prove protective in infancy.
PAIN MANAGEMENT Prevention Because all painful episodes cannot be prevented, patients should know how to manage mild pain and should be taught to recognize symptoms suggestive of serious problems. Optimal management of patients with painful events requires adequate education of the patient, family, and health care providers. Conditions that expose the patient to hypoxia, dehydration, and extreme cold should be avoided. Mountain climbing, flying in unpressurized aircraft, and swimming in frigid water are potentially hazardous. If air travel is necessary, patients should be advised to travel in pressurized aircraft, refrain from alcohol consumption, maintain an increased fluid intake, move about the plane periodically, and stay warm. Fluid intake (juices, soft drinks, and bouillon) should be increased during fevers, high ambient temperatures, and increased physical activity.Exchange transfusion to decrease the level of Hb S to less than 30 percent may help to prevent progression of the acute stroke. In addition to transfusions, it is important to provide rehabilitation services to the patient. Although many children may exhibit remarkable recovery from a stroke, a detailed assessment of intellectual function should be done to determine if the child would benefit from special assistance with academic work because acquired learning difficulties may be the consequence of the stroke. PREVENTION OF RECURRENT OCCLUSIVE STROKE Vasoocclusive strokes will recur in at least twothirds of patients, unless they are placed on a chronic program. Transfusions of packed red blood cells given at regular intervals to keep the level of Hb S below 30 percent are effective in minimizing a recurrence of cerebral infarction in children. A transfusion program should be maintained for a minimum of 5 years. Should neurologic symptoms develop in adequately transfused patients, repeat imaging studies are warranted. The optimal duration of transfusion therapy is not known. The risk of recurrence in untransfused children is greatest in the first 3 years after the initial event. Many centers transfuse patients for years but modify the intensity of transfusions to reduce the rate of iron accumulation. Centers that transfuse patients for long periods use ironchelating agents (deferoxamine mesylate) to decrease iron overload. Prognosis for longterm neurologic function and independent selfsufficient adult life is guarded. The role of bone marrow transplantation as an alternative therapy for these patients is unclear at present.Inadequate transfusion therapy, as defined by a failure to suppress Hb S below 30 percent, may be due to inadequate frequency of transfusions, poor compliance, development of alloimmune or autoimmune antibodies, or blood loss. Although aspirin or coumadin therapy has been effective in decreasing the risk of recurrent stroke in adult patients with normal hemoglobin (AA), or in those who have had prior TIA, the efficacy of such therapy in central nervous system disease in patients with sickle cell disease has not been established. EXPERIMENTAL THERAPY There has been no established method of treatment for the prevention of vasoocclusive pain crisis and other complications of sickle cell disease. A number of experimental therapeutic approaches, including use of hydroxyurea, erythropoietin combined with hydroxyurea, shortchain fatty acids (such as butyrate derivatives), and clotrimazole, are currently under investigation, Experimental Therapy). |
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