Lab Profiles UPDATED




Sickle Cell Anemia/Hemoglobinopathies
 
Condition: Sickle Cell Anemia/Hemoglobinopathies

Hemoglobinopathies (including Sickle Cell Diseases) are caused by abnormalities of a child's hemoglobin. Hemoglobin is the component of red blood cells which carries oxygen and abnormalities often lead to infections and further complications. Treatment in the form of antibiotics has proven effective.



More technical information from the Mountain States Genetic Network:



Most clinically significant hemoglobinopathies are inherited defects of the ß globin chain of adult hemoglobin. While some ß globin (and hence adult hemoglobin) is present at birth, red blood cells of newborns have a predominance of fetal hemoglobin which does not contain ß globin. For this reason, clinical signs and symptoms of ß globin abnormalities are usually not apparent at birth but become evident later after adult hemoglobin replaces fetal hemoglobin.



Most of the ß globin variants detected by newborn screening are the result of single amino acid substitutions and are inherited as autosomal recessive disorders. Individuals with one abnormal ß globin gene (heterozygotes) are said to have a hemoglobin trait and are carriers for disease. Persons with two abnormal ß globin genes, homozygotes (e.g., sickle cell anemia) or compound heterozygotes (e.g., sickle hemoglobin C disease), have disease. Other serious hemoglobinopathies, such as sickle ß -thalassemia, result from the coinheritance of some ß globin variants (e.g., sickle hemoglobin) with ß thalassemia.



Thalassemias are caused by the decreased synthesis of the globin chains. Infants with a thalassemia are often identified by newborn screening because Barts hemoglobin (composed of four gamma chains) is readily detected. The clinical severity of a thalassemia varies from the silent carrier state with no clinical or hematologic manifestations to hydrops fetalis with perinatal mortality. In contrast to a thalassemia, most infants with ß thalassemia (i.e., ß thalassemia trait) are not identified by newborn screening (exceptions include infants with hemoglobin E or hemoglobin Lepore).



The frequency of hemoglobinopathies varies among ethnic groups. Sickle hemoglobin is found most commonly in descendants of people from Africa, the Mediterranean basin, the Middle East, and India. In the U.S. sickle hemoglobin is encountered in virtually all ethnic groups. Hemoglobin C occurs most commonly in descendants of central and western Africans. Hemoglobin E is common in persons of southeast Asian ancestry. Thalassemia genes (alpha and ß ) originated in west and central Africa, the Mediterranean basin, the Middle East, south Asia, southeast Asia, southern China, and the Pacific Islands.





Clinical Features

Sickle cell diseases occur in persons homozygous for the sickle gene (sickle cell anemia), in compound heterozygotes for sickle hemoglobin and hemoglobin C (hemoglobin SC disease), and in compound heterozygotes for sickle hemoglobin and ß thalassemia (sickle ß -thalassemia). Persons who inherit hemoglobin S with hemoglobin CHarlem ,D, E, or O also have a sickling disease. Infants with sickle cell diseases may present with dactylitis, fever and sepsis, jaundice, anemia, or splenic sequestration at any time after the age of 2-3 months. Other complications, including recurrent pain, acute chest syndrome, stroke, cholelithiasis, priapism, and aseptic necrosis of bone, occur as the disease progresses. These disorders are heterogeneous in severity, and all clinical features are not present in all affected individuals.

The clinical features of other (non-sickle) hemoglobin diseases vary. Homozygous hemoglobin C causes mild hemolytic anemia. Homozygous hemoglobin E causes microcytosis and sometimes mild anemia. Persons with thalassemias have varying degrees of microcytic, hypochromic anemia and those with severe forms (e.g., homozygous ß thalassemia, HbE ßo-thalassemia) develop severe anemia and may be transfusion dependent.



Most hemoglobin traits (heterozygous carriers) are not associated with any clinical problems. Thus, the value of carrier detection is the opportunity to educate families, to test other family members, and to offer genetic counseling.





Laboratory Tests

Screening is performed by isoelectric focusing (IEF) of a hemolysate prepared from a dried capillary blood spot (New Mexico screens with HPLC and confirms with IEF). Individual hemoglobins (or "bands") are identified by their migration in the electrophoretic field.

Confirmatory testing is always necessary to adequately diagnosis a hemoglobin disease or trait. Some states use a repeat hemoglobin electrophoresis by IEF plus citrate agar. Others use cellulose acetate and citrate agar. In some cases testing of parents may be helpful in clarifying the infant's hemoglobin phenotype. Solubility testing (sickle prep or sickledex) should never be used as a confirmatory test.



Treatment

Treatment for sickle cell diseases includes the following:

Education and genetic counseling for parents.

Overall medical management should be planned in consultation with a comprehensive sickle cell center or a pediatric hematologist.

Penicillin prophylaxis, 125 mg p.o. bid, started by 2 months of age for children with sickle cell anemia and

sickle ß o-thalassemia.

Prompt medical evaluation, including appropriate cultures and parenteral antibiotics (e.g., ceftriaxone), for all significant febrile illnesses (T >101o).

Prompt medical evaluation for signs and symptoms of splenic sequestration.

Routine immunizations plus pneumococcal vaccine at 2 and 5 years of age.

Other treatments, including red cell transfusion, are based on clinical course.



Treatment for other hemoglobin diseases is usually determined by the severity of the anemia.



Screening Practice Considerations

The primary purpose of hemoglobinopathy screening is the identification of infants with sickle cell diseases for whom early intervention has been shown to markedly reduce morbidity and mortality. The screening test is not diagnostic, and confirmation of all abnormal results should be obtained by hemoglobin electrophoresis. Blood transfusion may cause false negative results and thus a newborn screen should always be obtained prior to a transfusion, regardless of the neonate's age. In cases where this is not accomplished, repeat hemoglobin electrophoresis should be obtained 3-4 months after the date of the last transfusion. Current screening methods do not detect many infants with thalassemias. Detection of infants with hemoglobin traits affords an opportunity for genetic counseling and for the identification of couples at risk for having subsequent children born with a disease.

Hemoglobinopathies are complex disorders, and practitioners are strongly encouraged to consult local program consultants and follow-up resources for additional information concerning abnormal screening test results and appropriate follow-up and treatment.