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Sickle Cell Disease Guideline Panel. Sickle Cell Disease: Screening, Diagnosis, Management, and Counseling in Newborns and Infants. Rockville (MD): Agency for Health Care Policy and Research (AHCPR); 1993 Apr. (AHCPR Clinical Practice Guidelines, No. 6.)

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

Cover of Sickle Cell Disease: Screening, Diagnosis, Management, and Counseling in Newborns and Infants

Sickle Cell Disease: Screening, Diagnosis, Management, and Counseling in Newborns and Infants.

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Overview

Introduction

Neonatal screening and comprehensive health care can significantly reduce morbidity and mortality in infants with sickle cell disease. In addition to saving lives and reducing morbidity, neonatal sickle cell disease screening has other benefits, including the identification of individuals with sickle cell trait and other hemoglobin disorders, as well as couples at risk for having a child with a hemoglobin disease.

This guideline makes specific recommendations about the population to be screened for sickle cell disease, the laboratory methods currently acceptable for screening and diagnosis, the care of infants with sickle cell disease, and the provision of educational and decision-making counseling services to parents of affected infants and those whose infants have sickle cell trait.

What is sickle cell disease?

The term sickle cell disease refers to a group of genetic disorders characterized by the presence of sickle hemoglobin , anemia, and acute and chronic tissue injury secondary to blockage of blood flow by abnormally shaped red cells. Normal hemoglobin, hemoglobin A , is composed of two alpha (a) globin chains and two beta (B) globin chains. In Hb S, the a chain is the same as in Hb A, but the B globin chain differs from the normal by the substitution of valine for glutamic acid at the sixth position (Bs). The most common type of sickle cell disease is sickle cell anemia in which the affected individual is homozygous for the Bs gene. Other common forms of sickle cell disease include the inheritance of the Bs gene and a gene for B-thalassemia (Hb S B-thalassemia) or another abnormal B globin gene. Examples of these latter conditions include Hb SC disease (Hb S and Hb C), Hb S OArab (HbS and Hb OArab) and Hb SD (Hb S and Hb D), and Hb SE (Hb S and Hb E) disease.

The hallmark features of sickle cell disease are chronic hemolytic anemia and both acute and chronic tissue injury. The amino acid substitution in the B globin of Hb S results in polymerization of the Hb S molecules within the red cell upon deoxygenation. This polymerization of Hb S produces a change in the red cell shape from a biconcave disc to a crescent or sickle shape. Upon reoxygenation, the red cell initially resumes a normal configuration, but after repeated cycles of sickling and unsickling, the erythrocyte is damaged permanently and hemolyzes. This hemolysis is responsible for the anemia in sickle cell disease.

The tissue injury is secondary to the obstruction of blood flow produced by the abnormally shaped red cells. All tissues within the body are at risk for damage as a consequence of the vascular obstruction produced by the sickled red cells. The more common complications include painful episodes involving soft tissues and bones, acute chest syndrome, priapism, cerebral vascular accidents, and both splenic and renal dysfunction. In sickle cell anemia, the splenic dysfunction develops during infancy and predisposes the infant to painful episodes involving soft tissues and bones, acute chest syndrome, priapism, cerebral vascular accidents, and both splenic and renal dysfunction. In sickle cell anemia, the splenic dysfunction develops during infancy and predisposes the infant to overwhelming infection from encapsulated bacteria, particularly members of the Streptococcus pneumoniae and Haemophilus influenzae species.

Who is affected by sickle cell disease?

Sickle cell disease is estimated to affect more than 50,000 Americans and has been identified in persons from several different racial backgrounds. The estimated prevalence of the common sickle cell disease variants in African-American live births is approximately 1 in 375 for sickle cell anemia, 1 in 835 for Hb SC disease, and 1 in 1,667 for the sickle B-thalassemia disorders. While sickle cell disease is most commonly found in persons of African ancestry, it also affects persons of Mediterranean, Caribbean, South and Central American, Arabian, and East Indian ancestry.

What is sickle cell trait?

In sickle cell trait, the individual has inherited both a normal B globin gene and a Bs globin gene. Individuals with sickle cell trait produce both normal hemoglobin and Hb S and have a predominance of Hb A. Red cells from persons with sickle cell trait do not sickle except under adverse circumstances. Persons with sickle cell trait have normal hemoglobin concentrations and normal red cell morphology. Approximately 8 percent of the African-American population in the United States has sickle cell trait. The prevalence of sickle cell trait is lower in other racial and ethnic groups.

Background

The passage of the National Sickle Cell Anemia Control Act in 1972 authorized funding for research, testing, and education related to sickle cell anemia. Funds appropriated within the budget of the National Heart, Lung, and Blood Institute, National Institutes of Health, established several federally funded sickle cell screening programs, as did monies from the Bureau of Maternal and Child Health, Health Resources and Services Administration. These early programs focused on detecting persons with sickle cell trait so that they could be educated about the trait and its genetic implications. Education and genetic counseling for persons with sickle cell trait were important components of these early programs.

Newborn screening for sickle cell disease began in the United States in the early 1970s. These initial screening programs grew out of the recognition that sickle cell anemia was associated with significant morbidity and mortality. In 1970, the estimated median expected survival was 20 years for affected persons living in the United States (Scott, 1970). With advances in the diagnosis, treatment, and prevention of complications, the life expectancy of persons with sickle cell disease has improved. Presently there is an 85 percent chance that infants with Hb SS will survive to age 20 and a 92 percent change that babies born with Hb SC will survive to a similar age, (Leikin, Gallagher, and Kinney, 1989).

The principal causes of death in infants with Hb SS disease are overwhelming infections with Streptococcus pneumoniae organisms, cerebral vascular accidents, and acute splenic sequestration crisis (Emond, Collis, Darvill, et al., 1985 ; Leikin, Gallagher, and Kinney, 1989). The predisposition to pneumococcal infection is secondary to the functional asplenia that develops within the first 2 years of life (Pearson, Gallagher, Chilcote, et al., 1985). Twice-daily oral penicillin reduces both the morbidity and mortality from pneumococcal infection (Gaston, Verter, Woods, et al., 1986). Teaching parents to recognize the early signs of splenic sequestration crisis should reduce deaths from this complication.

Although laboratory procedures to detect sickle hemoglobin in newborns have been available for nearly two decades, neonatal screening for sickle cell disease was not widely implemented by State screening programs until the late 1980s (Garrick, Dembure, and Guthrie, 1973 ; Gilman, McFarlane, and Huisman, 1976 ; Schneider, Gustafson, and Haggard, 1970). Arguments against neonatal screening included the contention that little could be done to reduce either morbidity or mortality once sickle cell disease was detected. This position prevailed despite evidence that early identification and entry into comprehensive care favorably affected overall morbidity and mortality (Powars, Overturf, Weiss, et al., 1981). The position was invalidated by a randomized controlled clinical trial which demonstrated that twice-daily oral penicillin reduced both mortality and morbidity from infectious complications of sickle cell anemia (Gaston, Verter, Woods, et al., 1986).

Following the report on the beneficial effects of prophylactic penicillin, the National Institutes of Health convened a Consensus Conference to review evidence about the benefits of newborn screening for sickle cell disease. The conference panel concluded that screening could reduce morbidity and mortality, provided the screening program was linked to the provision of comprehensive health care services to affected infants (Consensus Conference, 1987).

Shortly after these findings were disseminated, sickle cell screening in the United States became widespread. The proliferation of screening programs was stimulated by funds from the Bureau of Maternal and Child Health which were earmarked to support screening programs that could demonstrate the ability of neonatal hemoglobinopathy screening to reduce morbidity and mortality. Today, newborn hemoglobinopathy screening is performed in more than 40 States, the District of Columbia, Puerto Rico, and the Virgin Islands. The remarkable growth in screening programs within the past few years illustrates how Federal and State partnerships can dramatically improve the quality of health care programs.

Purpose of the Guideline

Although the findings of the Consensus Conference were published 6 years ago, there remain many unresolved issues surrounding neonatal sickle cell disease screening related to:

  1. Definition of the essential screening program components and their respective responsibilities.
  2. Definition of the population to be screened.
  3. Standards for sample identification, collection, and shipment.
  4. Standards for laboratory methods, quality control, quality assurance, and result reporting.
  5. Education and genetic counseling services for the parents of identified heterozygotes and infants with disease.
  6. Medical care for infants with sickle cell disease.
  7. Cost effectiveness of neonatal sickle cell screening.

This guideline was developed to address each of these problematic areas. The guideline emphasizes the required components for a program, defines the population to be screened, addresses important laboratory and genetic counseling issues, and describes essential health services for infants identified with sickle cell disease. The guideline also discusses the cost effectiveness of neonatal screening for sickle cell disorders.

The panel recognizes that financial constraints may prevent a particular screening program from meeting all recommendations within the guideline. This guideline, however, provides the framework for the implementation and conduct of a screening program that will achieve the ultimate objective of reducing infant morbidity and mortality from sickle cell disease.

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