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 sickle cell disease, S/C Disease and S,Beta-Thalassemia; however, only 87% of states screen for other hemoglobinopathy types.
  • Prenatal screening is often performed on high-risk parents with an ethnic background associated with a higher prevalence of hemoglobin disorders 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 (CZE)
• 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 variants 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 you have a genetic variant and whether there is one or two copies of the variant (heterozygous or homozygous).

Testing for specific 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 suggest that you have an abnormal form of hemoglobin.

Testing may be ordered when a healthcare practitioner suspects that your 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, which is yellowing of the eyes and skin
• 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. Hemoglobin test costs vary based on specific test type and how it is taken.

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

Less common forms often are named after the location of the family or families in whom the genetic variant was first identified (i.e.. 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).

Two different abnormal genes can be inherited, 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 (symptoms can mimic sickle cell disease), hemoglobin E – beta thalassemia, and hemoglobin S – beta thalassemia.

The following table provides some examples of results that may be seen with a hemoglobinopathy evaluation:

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 certain hemoglobin variants (i.e., Hb S, SC and beta-thalassemia), they have uncovered thousands of children who are carriers. (This is due to new technology, not to an increased prevalence of the gene variants.) Information on carrier status may be important in their future if and when they begin to plan a family.

Blood transfusions can interfere with hemoglobinopathy evaluation because any of the methods will detect both the blood donor and your hemoglobin forms, potentially hindering the results. 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 and prevent sickle cell crisis.

It depends on the method of testing and the laboratory performing the evaluation. This testing requires specialized equipment and interpretation, thus not every laboratory performs this test. Your sample may be sent to a reference laboratory, so it may take several days before results are available.

Treatment for certain types of hemoglobin disorders may involve supportive care, for example during a sickle cell crisis. The aim is to relieve pain and minimize complications. Sometimes blood transfusions are needed if there is severe anemia. There are some other less common treatments that are available.