A fetal hemoglobin test (Hgb electrophoresis) measures the level of fetal hemoglobin (Hemoglobin F or HbF) in the blood of infants and children. It can also be measured in adults, though is more typically needed for diagnoses of congenital illnesses in children. Fetal hemoglobin, an alkali-resistant form of hemoglobin, is the major hemoglobin component in the bloodstream of the fetus. After birth, it decreases rapidly until only traces are found in healthy children and adults. Fetal hemoglobin is one of six types of hemoglobin measured in the clinical laboratory by a method called hemoglobin electrophoresis.
Purpose
The determination of fetal hemoglobin in the blood of infants and children identifies normal and abnormal levels, defining what percentage of total hemoglobin is made up of fetal hemoglobin. Knowing this level may help doctors evaluate low concentrations of normal hemoglobin in red blood cells (anemia), as well as higher-than-normal levels of fetal hemoglobin or its hereditary persistence. Fetal hemoglobin measurement helps diagnose a group of inherited disorders that affect hemoglobin production, among which are the thalassemias and sickle cell anemia. It may also be done to help doctors diagnose acquired illnesses such as acquired hemolytic anemia, leukemia, pernicious anemia, and certain types of cancer.
Description
Hemoglobin is the oxygen-carrying protein in red blood cells. It is also the pigment that gives red blood cells their color. Red blood cells deliver hemoglobin throughout the body, ensuring that all body tissues have the oxygen they need for life and proper function. Hemoglobin consists primarily of iron-bearing proteins called heme groups and moiety globin protein, which together give hemoglobin its ability to carry oxygen. The heme groups are molecular chains of different types and actually create six different hemoglobins that vary in their amino acid composition and also in the genes that control them. Among the six types of hemoglobin, HbA is the normal adult hemoglobin, and HbF is the major fetal hemoglobin. Abnormal types of hemoglobin include Hgb S and Hgb C. All types of hemoglobin are electrically charged, which enables them to be identified and quantified in the laboratory by hemoglobin electrophoresis techniques.
During fetal development, fetal hemoglobin composes about 90 percent of total hemoglobin. At birth, the newborn's blood is composed of about 70 percent fetal hemoglobin. As the infant's bone marrow begins to produce new red cells, fetal hemoglobin begins to decrease rapidly. Normally, only 2 percent or less of total hemoglobin is found as fetal hemoglobin after six months and throughout childhood; in adulthood, only traces (0.5% or less) are found in total hemoglobin.
In some diseases associated with abnormal hemoglobin production (hemoglobinopathy), fetal hemoglobin may persist in larger amounts. When this occurs, the increased amounts of fetal hemoglobin raise questions of possible underlying dysfunction or disease. For example, HbF can be found in higher levels in sickle cell anemia and other hereditary anemias. It has also been reported to be elevated in some other conditions such as leukemia, pregnancy, diabetes, thyroid disease, and sometimes as a side effect of anticonvulsant therapy. It may also reappear in adults when the bone marrow is overactive, as in disorders such as pernicious anemia, multiple myeloma, and invasive (metastatic) cancer affecting bone marrow. When HbF is elevated after age four, the cause is typically investigated. (Persistence of fetal hemoglobin in inherited hemolytic anemias can be associated with less severe disease symptoms.)
Defects in hemoglobin production may be either genetic or acquired. The genetic defects are subdivided
into errors of heme production (porphyria) and those of globin production, known collectively as the hemoglobinopathies. There are two categories of hemoglobinopathy: in one, abnormal globin chains give rise to abnormal hemoglobin molecules; in the other, normal hemoglobin chains are produced but in abnormal amounts. Sickle cell anemia, the inherited condition characterized by curved (sickle-shaped) red blood cells and chronic hemolytic anemia, is an example of the first category. Disorders in the second category are called the thalassemias, which are classified according to which amino acid chain, alpha or beta, is affected, and whether one defective gene (thalassemia minor) or two defective genes (thalassemia major) are responsible for the disorder. Testing for levels of fetal hemoglobin and other types of hemoglobin may be a first, important step in the investigation of possible hemoglobinopathies.
Levels of HbF are of interest in diagnosing several hemoglobinopathies, including the following:
thalassemia minor or thalassemia trait (heterozygous thalassemia), in which HbF does not decrease normally after birth and may remain high in later life
thalassemia major (homozygous thalassmia or Cooley's anemia), the hereditary persistence of HbF involving larger than normal amounts of HbF
sickle cell anemia associated with the abnormal Hgb S, which occurs primarily in African-Americans; also Hgb C, another abnormal hemoglobin found in African-Americans, causing hemolytic anemia
beta-chain hemoglobinopathies with increased HbF during childhood
disease-related hematologic stress as in hemolytic anemias, leukemia, and aplastic anemia
Parents may wish to explain the blood-drawing procedure to older children to help prepare them for the slight discomfort they will experience.
Testing for fetal hemoglobin requires that a blood sample be drawn from the child. No preparation is needed before performing fetal hemoglobin tests, and fasting (nothing to eat or drink for a period of hours before the test) is not required. Proper identification and careful handling of the child are important when a blood sample is being obtained for testing. A site, usually the heel on an infant and a finger on an older child, is chosen by the phlebotomist who will draw the blood. A baby's foot may be wrapped in a warm cloth for a few minutes to bring blood to the surface and allow it to flow more easily. The baby's heel or child's finger is then wiped with alcohol and/or an antibacterial solution such as betadine to sterilize the surface. Puncture is performed quickly with a lancet, avoiding the center of an infant's heel to prevent inflammation of the bone. The blood sample is drawn into tiny capillary tubes, properly labeled, and taken to the laboratory for testing. In rare instances, a phlebotomist will not be able to draw sufficient blood from an infant's heel puncture, and a physician may draw venous blood from a femoral vein in the groin area, which is larger than veins in an infant's arms. Older children may also have venous blood drawn, particularly if other blood tests are being done.
Aftercare
Pressure is applied to the blood-drawing site for a few minutes to prevent bleeding. The site of heel stick, finger stick, or venipuncture must be kept clean and dry and observed for any undue bleeding or bruising. A small bandage can be used to cover the site. Any unusual conditions or reactions should be reported to the pediatrician.
Risks
Risks for this test are minimal but may include slight bleeding from the blood-drawing site or blood may accumulate under the puncture site (hematoma). Fainting, nausea, or feeling lightheaded after venipuncture may occur in some children.
Normal results
Reference values vary from laboratory to laboratory but results of hemoglobin electrophoresis are generally reported within the following ranges:
Newborn to six months: HbF may be up to 70 percent of total hemoglobin.
Six months to adult: HbF may be up to 2 percent of total hemoglobin.
Levels of HbF greater than 2 percent of total hemoglobin is abnormal after the age of six months. Some hemoglobinopathies have elevated levels of other types of hemoglobin and normal levels of HbF as shown below.
Typical results for certain hemoglobinopathies include:
Sickle cell trait: Hemoglobin S 20–40%, Hgb A 60–80%, HbF 2%.
Hgb C disease: Hgb C 90–100%, Hgb A 0%, and Hb F 2%.
Thalassemia major: HbF 65–100%, Hgb A 5–25%.
Thalassemia minor: HbF 1–3%, Hgb A 50–90%.
Parental concerns
Children generally respond well to blood-drawing procedures if they are prepared for the slight discomfort. If parents are concerned about the possibility of inherited blood disorders, it may be helpful to remember that abnormal levels of fetal hemoglobin may be caused by a variety of conditions, not all of which are inherited or serious, and early recognition of a blood condition usually leads to early treatment and effective management of the condition.
KEY TERMS
Anemia—A condition in which there is an abnormally low number of red blood cells in the bloodstream. It may be due to loss of blood, an increase in red blood cell destruction, or a decrease in red blood cell production. Major symptoms are paleness, shortness of breath, unusually fast or strong heart beats, and tiredness.
Hemoglobinopathy—A disorder of hemoglobin, which can be either the presence of abnormal types of hemoglobin or abnormal levels of specific types of hemoglobin.
Hemolytic anemia—A form of anemia characterized by chronic premature destruction of red cells in the bloodstream. Hemolytic anemias are classified as either inherited or acquired.
Heterozygote/Heterozygous—Having two different versions of the same gene.
Homozygote/Homozygous—Having two identical copies of a gene.
Chernecky, Cynthia C., et al. Laboratory Tests and Diagnostic Procedures. Philadelphia, PA: Elsevier—Health Sciences Division, 2003.
Fischback, Frances Talaska. Manual of Laboratory and Diagnostic Tests. Hagerstown, MD: Lippincott Williams & Wilkins, 2004.
Nicoll, Diana, et al. Pocket Guide to Diagnostic Tests. Backlick, OH: McGraw-Hill Professional Publishing, 2003.
ORGANIZATIONS
The National Institutes of Health. 9000 Rockville Pike, Bethesda, MD 20892. Web site: <www.nih.gov>.
WEB SITES
"An Introduction to Genetics and Genetic Testing." Kids Health, 2004. Available online at <www.kidshealth.org/parent/system/medical/genetics.html> (accessed January 12, 2005).
