Hemoglobinopathy Evaluation

A hemoglobinopathy evaluation is used to detect abnormal forms and/or relative amounts of hemoglobin, the protein found in all red blood cells that transports oxygen. Testing may be used for:

• Screening
  • All states require that newborns be screened for certain hemoglobin variants.
  • Prenatal screening is often performed on high-risk parents with an ethnic background associated with a higher prevalence of hemoglobin abnormality and those with affected family members. Screening may also be done in conjunction with genetic counseling prior to pregnancy to determine whether the parents are carriers.
  • To identify variants in asymptomatic parents who have an affected child
• Diagnosis
  • To detect and/or identify hemoglobinopathy (hemoglobin abnormality or thalassemia) in those with symptoms of unexplained anemia or abnormal results on a complete blood count (CBC) 

Several different laboratory methods are available to evaluate the types of hemoglobin that a person has. Some of these include:

• Hemoglobin solubility test: used to test specifically for hemoglobin S, the main hemoglobin in sickle cell disease
• Hemoglobin gel electrophoresis (Hb ELP)
• Hemoglobin isoelectric focusing (Hb IEF)
• Hemoglobin by high performance liquid chromatography (HPLC)
• Hemoglobin by capillary zone electrophoresis
• Hemoglobin by mass spectrometry

These methods evaluate the different types of hemoglobin based on the physical and chemical properties of the different hemoglobin molecules.

Most of the common hemoglobin variants or thalassemias can be identified using one of these tests or a combination. The relative amounts of any variant hemoglobin detected can aid in a diagnosis. However, a single test is usually not sufficient to establish a diagnosis of hemoglobinopathy. Rather, the results of several different tests are considered. Examples of other laboratory tests that may be performed include:

• CBC
• Blood smear
• Reticulocyte count
• Iron studies such as serum iron, TIBC, transferrin
• Genetic testing: may be used to detect mutations in the genes that code for the protein chains (alpha and beta globulin) that comprise hemoglobin. This is not a routine test but can be used to confirm whether a person has a mutated gene and whether there is one or two mutated copies (heterozygous or homozygous).

Testing for hemoglobinopathies is required as part of state-mandated newborn screening. In addition, it is often used for prenatal screening when a parent is at high risk or when parents have a child who has a hemoglobinopathy.

An evaluation is usually ordered when results of a complete blood count (CBC) and/or blood smear indicate that a person may have an abnormal form of hemoglobin.

It may be ordered when a healthcare practitioner suspects that a person's signs and symptoms are the result of abnormal hemoglobin production. Abnormal forms of hemoglobin often lead to hemolytic anemia, resulting in signs and symptoms such as:

• Weakness, fatigue
• Lack of energy
• Jaundice
• Pale skin

Some severe forms of hemoglobinopathies (e.g., sickle cell disease) may result in serious signs and symptoms, such as episodes of severe pain, shortness of breath, enlarged spleen, and growth problems in children.

Care must be taken when interpreting the results of a hemoglobinopathy evaluation. Typically, the laboratory report includes an interpretation by a pathologist with experience in the field of hematology (hematopathologist).

Results of the evaluation usually report the types of hemoglobin present and the relative amounts. For adults, percentages of normal hemoglobin include:

• Hemoglobin A1(HB A1): about 95%-98%
• Hemoglobin A2 (Hb A2): about 2%-3%
• Hemoglobin F (Hb F): 2% or less

Some of the most common abnormal forms of hemoglobin that may be detected and measured with this testing include:

• Hemoglobin S (Hb S, sickle cell disease or trait)
• Hemoglobin C (Hb C)
• Hemoglobin E (Hb E)

Some less common forms include:

• Hemoglobin F (Hb F): Hb F may be elevated in several disorders, such as beta thalassemia and sickle cell anemia.
• Hemoglobin H (Hb H)
• Hemoglobin Barts

Other types that may be identified include:

• Hemoglobin D
• Hemoglobin G
• Hemoglobin J
• Hemoglobin M
• Hemoglobin Constant Spring

Testing may help identify thalassemia by detecting abnormal hemoglobin (e.g., hemoglobin H in alpha thalassemia) or an increase of minor hemoglobin components, such as Hb A2 or Hb F (beta thalassemia).

A person can also inherit two different abnormal genes, one from each parent, that may result in a combination of abnormal hemoglobins detected by testing. This is known as being compound heterozygous or doubly heterozygous. Clinically significant combinations — those that result in significant signs and symptoms — include hemoglobin SC disease, hemoglobin E – beta thalassemia, and hemoglobin S – beta thalassemia.

For more information on these conditions, see the articles on Hemoglobin Abnormalities and Thalassemia.

Some examples of results that may be seen with a hemoglobinopathy evaluation are listed in the following table.

Blood transfusions can interfere with hemoglobinopathy evaluation. You should wait several months after a transfusion before having this testing done. However, in people with sickle cell disease, the testing may be performed after a transfusion to determine if enough normal hemoglobin has been given to reduce the risk of damage from sickling of red blood cells.

Newborn screening helps to identify potentially treatable or manageable congenital disorders within days of birth. Potentially life-threatening health problems and serious lifelong disabilities can be avoided or minimized if a condition is quickly identified and treated. Also, since newborn screening programs have mandated testing for hemoglobin variants, they have uncovered thousands of children who are carriers. (This is due to new technology, not to an increased prevalence of the gene mutations.) Information on carrier status may be important in their future if and when they begin to plan a family.