Tables 1. Prevalence per 100,000 population of sickle cell disease (Hb SS, Hb SC, Hb S/B-thalassemia) by race and/or ethnic group 2. Prevalence per 100,000 population of sickle cell trait (AS) 3. Prevalence per 100,000 population of doubly heterozygous 4. Prevalence per 100,000 population of other hemoglobinopathy 5. Screening methods . 6. Types of blood samples for hemoglobin screening tests 7. Sensitivity of laboratory methods for detecting hemoglobinopathy disease in newborns 8. Specificity of laboratory methods for detecting hemoglobinopathy disease in newborns 9. Results of repeated testing of same newborn specimen 10. Hemoglobin patterns 11. Comparison of sample types for confirmation tests 24 26 28 28 32 of hemoglobin screening. 12. Comparison of testing methods for confirmation tests 13. Mortality from pneumococcal sepsis in different clinical settings.. 40 14. Morbidity and mortality in controlled trials of penicillin prophylaxis and pneumococcal vaccine in children with sickle cell disease 15. Incidence of splenic sequestration in children with sickle cell disease 41 44 16. Counseling on the nature of sickle hemoglobinopathies 18. Counseling of individuals with sickle cell trait for family planning and decision making 56 Figure 1. Meta-analysis of CORN data on prevalence of sickle cell disease among black populations 17 Executive Summary Introduction This Clinical Practice Guideline on Sickle Cell Disease was developed by a private-sector panel of internists, pediatricians, nurses, a family physician, geneticists, a social worker, a person with sickle cell disease, and the parent of a child with sickle cell disease. The panel was convened and supported by the Agency for Health Care Policy and Research, Public Health Service, U.S. Department of Health and Human Services. The guideline makes specific recommendations about the newborn population to be screened for sickle cell disease, laboratory methods for screening and diagnosing the disease, medical management of affected individuals, and counseling of parents whose children have sickle cell disease or trait. The guideline is based on the best science available. Using the panel's literature search outline, data base specialists at the National Library of Medicine conducted a comprehensive literature search that yielded the titles, and usually the abstracts, of more than 7,000 relevant publications. Of these, over 2,000 papers and monographs were selected for further consideration; hundreds of these were used by the panel in formulating its recommendations. In addition, both oral and written suggestions for elements to be included in the guideline were solicited during an open forum held in Washington, DC, on September 24, 1991. Drafts of the guideline document were submitted for peer review to individuals and organizations representative of the spectrum of components required for a screening program. Peer reviewers assessed its validity, efficacy, and applicability. Most recommendations from this peer review were incorporated into the final document. Background Sickle cell disease is a term for a group of genetic disorders characterized by production of hemoglobin S (Hb S), anemia, and acute and chronic tissue damage secondary to the blockage of blood flow produced by the abnormally shaped red cells. Sickle cell anemia (Hb SS) is the most common type of sickle cell disease and is estimated to affect more than 50,000 Americans. The estimated prevalence of Hb SS in African-American live births is approximately 1 in 375; other common variants of the disease include hemoglobin SC disease (Hb SC)—with an estimated prevalence of 1 in 835 African-American live births-and sickle beta-thalassemia (S B-thalassemia)—1 in 1,667 African-American live births. In the United States, sickle cell disease is most commonly found in persons of African ancestry, but it also affects persons of Mediterranean, Caribbean, South and Central American, Arabian, and East Indian ancestry. Sickle cell trait is characterized by the inheritance of a normal ẞ globin gene and a ẞ globin gene. Persons with sickle cell trait produce both normal hemoglobin (Hb A) and sickle hemoglobin but have a predominance of Hb A. When both parents have sickle cell trait, there is a 25 percent chance with each pregnancy that the infant will have sickle cell anemia. Guideline Recommendations This guideline on sickle cell disease provides specific recommendations for newborns and infants in several areas, including: 1. Population to be screened. 2. Laboratory methods and responsibilities. Population To Be Screened The panel recommends screening all newborns regardless of racial or ethnic background for sickle cell disease. This recommendation is based on several factors. First, twice-daily oral prophylactic penicillin reduces both morbidity and mortality from pneumococcal infections in infants with sickle cell anemia and sickle beta°-thalassemia. Second, although sickle cell disease is more prevalent in certain racial and ethnic groups, it is not possible to define accurately an individual's heritage by physical appearance or surname. Screening targeted to specific racial and ethnic groups, therefore, will miss some affected infants, subjecting them to an increased risk of early mortality. Third, screening should benefit all babies equally, as State-sponsored newborn screening programs in the United States are supported at least in part by public funds and often are mandated by State law. Universal screening is the best and most reliable method for casting the broadest possible net to identify affected infants. In addition to ensuring that all infants benefit equally from the screening program funded by State or Federal money, universal screening also is the most costeffective screening method. Laboratory Testing and Responsibilities When feasible, laboratory testing should be linked to other neonatal screening programs to facilitate specimen collection, identification, and handling. There is no single "best" laboratory method for screening. Several techniques—including hemoglobin electrophoresis, isoelectric focusing, and high performance liquid chromatography-are acceptable, reliable, and accurate. Recent reports have advocated globin DNA analysis as an additional testing method. At present, this method is both costly and limited in the number of genotypes that can be identified. Metabisulfite sickle cell preparations and Hb S solubility testing, however, are not acceptable screening methods. The screening methodology should be selected in light of the program's available resources and knowledge of the technique and its limitations. The screening laboratory should participate in quality assurance and proficiency testing programs, regardless of the technique employed. The initial screening sample should not be used to establish a definitive diagnosis for infants with suspected disease. A second sample must be collected from the infant to establish a diagnosis. Definitive diagnosis should be made by the physician caring for the infant using consultation as needed. Techniques to establish the definitive diagnosis include reassessment of the infant's hemoglobin phenotype, measurement of hemoglobin concentration and red cell indices, inspection of the red cell morphology, and correlation with the clinical history. Assessment of the hemoglobin phenotypes of the parents, including the amounts of fetal hemoglobin and hemoglobin A, and the distribution of fetal hemoglobin within the parents' red cells, is useful in assigning a definitive diagnosis when both parents are available for study. Definitive diagnosis also can be established in some cases by direct analysis of the infant's globin DNA. The laboratory should be responsible for sending test results to the health provider of record, the screening program's administrative component, and when applicable, the infant's hospital of birth. When permitted by law, test results also should be sent to the infant's mother. Reporting of results should include the hemoglobin phenotype, mention the diagnostic possibilities associated with the phenotype, and identify sources where additional information can be obtained. Medical Followup Pneumococcal infections in infants with sickle cell anemia and sickle Bo-thalassemia account for significant morbidity and mortality. It has been documented unequivocally that these infections are reduced significantly by the administration of twice-daily oral penicillin. For this inexpensive and effective therapy to be beneficial, infants identified by screening must be located promptly, definitively diagnosed, and given penicillin. Parents must be educated as to the necessity for complying with this treatment. Parents also must be taught to recognize early signs of specific complications of sickle cell disease and be provided with anticipatory guidance related to the management of these complications. Specific instructions should be given in the recognition of fever, splenic sequestration crisis, respiratory distress, and dehydration. Parents should be taught to take the infant's temperature and be provided with specific guidelines for oral fluid therapy, analgesics, and antipyretics. A trusting relationship between the infant's health care provider and parent is |