Guideline: Laboratory Screening 2 for Sickle Cell Disease The laboratory must use a screening procedure that will detect sickle hemoglobin in the newborn. The laboratory has a responsibility to transmit the infant's results to the infant's health care provider and hospital of birth. Test results must be reported in understandable language that includes the identified phenotype, diagnostic possibilities, and sources where additional information may be obtained. The laboratory also should inform the infant's mother of the screening result, unless prohibited by law. The laboratory is responsible for detecting conditions in which sickle hemoglobin (Hb S) is present. The primary goal is to screen for sickle cell disease, including its common forms: sickle cell anemia (Hb SS), sicklehemoglobin C disease (Hb SC), S beta*-thalassemia (Hb S ẞ*-thalassemia), and S beta-thalassemia (Hb S B°-thalassemia), as well as uncommon types such as Hb S-D Punjab, Hb S/O Arab, Hb S/Lepore, and Hb SE. Screening also will identify persons with sickle cell trait, hemoglobin C trait and disease, hemoglobin E trait, and Hb E disease. Other laboratory responsibilities include accurate recordkeeping, the results reporting process, and quality assurance. Background The principal hemoglobin in the newborn is fetal hemoglobin (Hb F). Hb F is composed of two alpha (a) and two gamma (y) globins. During the last trimester, there is a progressive increase in ẞ globin synthesis and a decrease in y chain synthesis. In the normal-term infant, about 80 percent of the non-a globin is y globin and 20 percent is ẞ globin. This accounts for the normal term infant having approximately 80 percent Hb F and 20 percent Hb A. Because the infant with sickle cell trait has both a normal B gene and a ẞs gene, the infant will have a predominance of Hb F and both Hb A and Hb S. There always will be more Hb A than Hb S in these infants because a chains preferentially pair with normal ẞ chains. In normal infants, y chain synthesis declines rapidly with a corresponding increase in ẞ globins. By 1 year of age, the normal infant will have only 1 to 2 percent Hb F and 95* percent Hb A. The remainder of the hemoglobin is Hb A2, composed of two a and two delta (8) globin chains. Electrophoresis is the most commonly used first step to characterize hemoglobin. Cellulose acetate and isoelectric focusing (IEF) are the most commonly used electrophoretic methods. Electrophoresis separates different hemoglobins by electrical charge. Many but not all high performance Cost-Effectiveness of Screening The cost-effectiveness of universal neonatal hemoglobinopathy screening is a complicated issue. Tsevat and colleagues (1991) found that the cost per life saved by universal screening would vary greatly among those populations with mixed racial composition. They equated the costeffectiveness of universal screening solely with the prevention of death from pneumococcal sepsis by the administration of prophylactic penicillin to infants whose sickle cell disease would otherwise have been unrecognized prior to age 3 years. Their adaptation of risk-reduction data from the Prophylactic Penicillin Study (PROPS), however, biased their results against a policy of early diagnosis (Gaston, Verter, Woods, et al., 1986). All patients in PROPS were known to have sickle cell disease prior to entry, and all were followed carefully; almost two-thirds of the patients were older than 12 months when enrolled. Further, the theoretical population on which Tsevat's most striking result was based does not correspond to any existing U.S. screening jurisdiction. Lane and colleagues (1992), using a computerized decision model to analyze their experience in Colorado, found that easily overlooked procedural and administrative costs associated with targeted screening could be high enough to make universal screening less expensive. Hidden costs included "loss of economy of scale in the screening laboratory and additional personnel costs for determining each infant's ethnic background." Sprinkle, Hynes, and Konrad (in press) projected the costs of finding cases of sickle cell disease in 53 U.S. jurisdictions (the 50 States, the District of Columbia, Puerto Rico, and the Virgin Islands) through universal neonatal hemoglobinopathy screening. They compared these costs to the costs projected for finding cases of phenylketonuria (PKU) through the universal neonatal screening practices long established for PKU in the same jurisdictions. Their estimates suggested that 35 jurisdictions would be able to find a case of sickle cell disease for less, often far less, than onehalf the cost of finding a case of PKU. The remaining 18 jurisdictions could substantially reduce the per-case costs, typically for finding both diseases, by combining efforts with other States. In fact, many States already have used this approach to reduce costs. States with relatively few African-Americans tended to be States with small populations in which the efficiency of screening for PKU and other metabolic diseases also could be enhanced by such combination, whether or not they decided to screen for hemoglobinopathies. States deciding to simplify the screening of neonates at high risk for sickle cell disease by testing all neonates, regardless of racial classification, would have little trouble finding demographically complementary screening “partners" with which to form low-cost screening composites. Issues for Future Research Although more than 40 States now screen for sickle cell disease, the number of States reporting usable data to CORN remains low. Much of the reported data are inconsistent or incomplete and could not be used in this analysis. Since the data reported here are not correlated with the type of screening program (universal vs. targeted), there is still some room for error. Improved and, more importantly, uniform methods for identifying and classifying subsets of the population are needed. Population subsets other than the general categories of blacks and whites still lack sufficient size to yield meaningful results. The prevalence among Hispanics, when analyzed by geographic area, reflects differences that should be substantiated with further data. In addition, researchers should investigate possible differences among Asians. An additional analysis of the costeffectiveness of sickle cell screening for low-risk populations should be undertaken. This analysis should use actual prevalence data and include the benefits of early detection of sickle cell disease beyond the life-saving effects of penicillin prophylaxis. Guideline: Laboratory Screening 2 for Sickle Cell Disease The laboratory must use a screening procedure that will detect sickle hemoglobin in the newborn. The laboratory has a responsibility to transmit the infant's results to the infant's health care provider and hospital of birth. Test results must be reported in understandable language that includes the identified phenotype, diagnostic possibilities, and sources where additional information may be obtained. The laboratory also should inform the infant's mother of the screening result, unless prohibited by law. The laboratory is responsible for detecting conditions in which sickle hemoglobin (Hb S) is present. The primary goal is to screen for sickle cell disease, including its common forms: sickle cell anemia (Hb SS), sicklehemoglobin C disease (Hb SC), S beta*-thalassemia (Hb S ẞ*-thalassemia), and S beta-thalassemia (Hb S B°-thalassemia), as well as uncommon types such as Hb S-D Punjab, Hb S/O Arab, Hb S/Lepore, and Hb SE. Screening also will identify persons with sickle cell trait, hemoglobin C trait and disease, hemoglobin E trait, and Hb E disease. Other laboratory responsibilities include accurate recordkeeping, the results reporting process, and quality assurance. Background The principal hemoglobin in the newborn is fetal hemoglobin (Hb F). Hb F is composed of two alpha (α) and two gamma (y) globins. During the last trimester, there is a progressive increase in ẞ globin synthesis and a decrease in y chain synthesis. In the normal-term infant, about 80 percent of the non-a globin is y globin and 20 percent is ẞ globin. This accounts for the normal term infant having approximately 80 percent Hb F and 20 percent Hb A. Because the infant with sickle cell trait has both a normal ß gene and a ẞs gene, the infant will have a predominance of Hb F and both Hb A and Hb S. There always will be more Hb A than Hb S in these infants because a chains preferentially pair with normal ẞ chains. In normal infants, y chain synthesis declines rapidly with a corresponding increase in ẞ globins. By 1 year of age, the normal infant will have only 1 to 2 percent Hb F and 95* percent Hb A. The remainder of the hemoglobin is Hb A2, composed of two a and two delta (8) globin chains. Electrophoresis is the most commonly used first step to characterize hemoglobin. Cellulose acetate and isoelectric focusing (IEF) are the most commonly used electrophoretic methods. Electrophoresis separates different hemoglobins by electrical charge. Many but not all high performance |