Also Known As
Haemoglobin Evaluation
Hb ELP
Hb IEF
Sickle Cell Screen
Formal Name
Haemoglobin Electrophoresis, Isoelectric Focusing or by HPLC
This article was last reviewed on
This article waslast modified on 27 June 2018.
At a Glance
Why Get Tested?

To investigate haemoglobinopathy as the cause of signs and symptoms; to screen for a haemoglobin disorder

When To Get Tested?

As follow up to abnormal results on a full blood count (FBC) and/or blood film; when you have symptoms of haemolytic anaemia such as weakness and fatigue and your doctor suspects that you have an abnormal form of haemoglobin (haemoglobinopathy); when you have a family history of haemoglobinopathy; as part of newborn screening

Sample Required?

A blood sample taken from a vein in your arm

Test Preparation Needed?

None

On average it takes 7 working days for the blood test results to come back from the hospital, depending on the exact tests requested. Some specialist test results may take longer, if samples have to be sent to a reference (specialist) laboratory. The X-ray & scan results may take longer. If you are registered to use the online services of your local practice, you will be able to access your results online.

If the doctor wants to see you about the result(s), you will be offered an appointment. If you are concerned about your test results, you will need to arrange an appointment with your doctor so that all relevant information including age, ethnicity, health history, signs and symptoms, laboratory and other procedures (radiology, endoscopy, etc.), can be considered.

Lab Tests Online-UK is an educational website designed to provide patients and carers with information on laboratory tests used in medical care. We are not a laboratory and are unable to comment on an individual's health and treatment.

Reference ranges are dependent on many factors, including patient age, gender, sample population, and test method, and numeric test results can have different meanings in different laboratories.

For these reasons, you will not find reference ranges for the majority of tests described on this web site. The lab report containing your test results should include the relevant reference range for your test(s). Please consult your doctor or the laboratory that performed the test(s) to obtain the reference range if you do not have the lab report.

For more information on reference ranges, please read Reference Ranges and What They Mean.

What is being tested?

A haemoglobinopathy is an inherited blood disorder in which an individual has an abnormal form of haemoglobin (variant) or decreased production of haemoglobin (thalassaemia). A haemoglobinopathy evaluation is a group of tests that identifies abnormal forms of or suggests problems with production of haemoglobin in order to screen for and/or diagnose a haemoglobin disorder.

Haemoglobin (Hb) is the iron-containing protein found in all red blood cells (RBCs) that binds to oxygen in the lungs and allows RBCs to carry the oxygen throughout the body, delivering it to the body's cells and tissues. Haemoglobin consists of one portion called haeme, which is the molecule with iron at the centre, and another portion made up of four globin (protein) chains. The globin chains, depending on their structure, have different designations: alpha, beta, gamma, and delta. The types of globin chains that are present are important in the function of haemoglobin and its ability to transport oxygen.

Normal haemoglobin types include:

  • Haemoglobin A: makes up about 95%-98% of Hb found in adults; it contains two alpha and two beta protein chains.
  • Haemoglobin A2: makes up about 2%-3% of Hb in adults; it has two alpha and two delta protein chains.
  • Haemoglobin F (foetal haemoglobin): makes up to 1%-2% of Hb found in adults; it has two alpha and two gamma protein chains. This is the primary haemoglobin produced by the foetus during pregnancy; its production usually falls shortly after birth and reaches adult levels by 1-2 years.

Haemoglobinopathies occur when changes (mutations) in the genes that code for the globin chains cause alterations in the proteins. These genetic changes may result in a reduced production of one of the normal globin chains or in the production of structurally altered globin chains. Genetic mutations may affect the structure of the haemoglobin, its behaviour, its production rate, and/or its stability. The presence of abnormal haemoglobin within RBCs can alter the appearance (size and shape) and function of the red blood cells.

Red blood cells containing abnormal haemoglobin (haemoglobin variants) may not carry oxygen efficiently and may be broken down by the body sooner than usual (a shortened survival), resulting in haemolytic anemia. Some of the most common haemoglobin variants include haemoglobin S, the primary haemoglobin in people with sickle cell disease that causes the RBC to become misshapen (sickle), decreasing the cell's survival; haemoglobin C, which can cause a minor amount of haemolytic anaemia; and haemoglobin E, which may cause no symptoms or generally mild symptoms.

Thalassaemia is a condition in which a gene mutation results in reduced production of one of the globin chains. This can upset the balance of alpha to beta chains, causing abnormal haemoglobin to form (alpha thalassaemia) or causing an increase of minor haemoglobin components, such as Hb A2 or Hb F (beta thalassaemia).

Many other less common haemoglobin variants exist. Some are silent – causing no signs or symptoms – while others affect the function and/or stability of the haemoglobin molecule. An investigation of a haemoglobin disorder typically involves tests that determine the types and amounts of haemoglobin present in a person's sample of blood. Some examples include:

  • Haemoglobin solubility test: used to test specifically for haemoglobin S, the main haemoglobin in sickle cell disease
  • Haemoglobin electrophoresis (Hb ELP)
  • Haemoglobin isoelectric focusing ( Hb IEF)
  • Haemoglobin by high performance liquid chromatography (HPLC)

Information from these tests, along with results from routine tests such as a full blood count (FBC) and blood film, aid in establishing a diagnosis.

How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm.

Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.

Accordion Title
Common Questions
  • How is it used?

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

    • Screening
      • All newborns are screened for certain hemoglobin variants.
      • Prenatal screening is often performed on high-risk parents with an ethnic background associated with a higher prevalence of haemoglobin abnormality and those with affected family members. Screening may also be done in conjunction with genetic counselling 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 haemoglobinopathy (haemoglobin abnormality or thalassaemia) in those with symptoms of unexplained anaemia or abnormal results on a full blood count (FBC)

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

    • Haemoglobin solubility test: used to test specifically for haemoglobin S, the main haemoglobin in sickle cell disease
    • Haemoglobin electrophoresis (Hb ELP)
    • Haemoglobin isoelectric focusing (Hb IEF)
    • Haemoglobin by high performance liquid chromatography (HPLC)

    These methods evaluate the different types of haemoglobin based on the physical and chemical properties of the different haemoglobin molecules. Most of the common haemoglobin variants or thalassaemias can be identified using one of these tests or a combination. The relative amounts of any variant haemoglobin detected can aid in a diagnosis. However, a single test is usually not sufficient to establish a diagnosis of haemoglobinopathy. Rather, the results of several different tests are considered. Examples of other laboratory tests that may be performed include:

  • When is it requested?

    Testing for haemoglobinopathies is required as part the national newborn screening program. 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 haemoglobinopathy. An evaluation is usually ordered when results of a full blood count (FBC) and/or blood film indicate that a person may have an abnormal form of haemoglobin.

    It may be requested when a doctor suspects that a person's signs and symptoms are the result of abnormal haemoglobin production. Abnormal forms of haemoglobin often lead to haemolytic anemia, resulting in signs and symptoms such as:

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

    Some severe forms of haemoglobinopathies (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.

  • What does the test result mean?

    Care must be taken when interpreting the results of a haemoglobinopathy evaluation. Typically, the laboratory report includes an interpretation by a haematologist.

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

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

    Testing may help diagnose a condition that causes the production of structurally altered haemoglobin (variant) or a condition called thalassaemia, in which a gene mutation results in reduced production of one of the globin chains. This can upset the balance of alpha to beta chains, causing abnormal haemoglobin to form (alpha thalassaemia) or causing an increase of minor haemoglobin components, such as Hb A2 or Hb F (beta thalassaemia).

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

    • Haemoglobin S (Hb S): this is the primary haemoglobin in people with sickle cell disease. Most people affected are of African or African-Caribbean origin. It is estimated that there are between 12,500-15,000 people with sickle cell disease in the UK according to the NICE guidance.

      Individuals with sickle cell disease (two copies of the abnormal gene) have a high percentage of Hb S. People with sickle cell trait have a moderate amount of Hb S (about 40%) but still have the normal form of Hb A (about 60%). Hb S causes the red blood cell to become misshapen (sickle) when exposed to a low level of oxygen (such as might happen when someone exercises or has infection in the lungs). Sickled red blood cells can block small blood vessels, causing pain, impaired circulation, and decreased oxygen delivery to tissues and cells, and decrease the cell's survival. High amounts of haemoglobin A or F can keep enough oxygen in the red blood cells to prevent sickling from occurring.

    • Haemoglobin C (Hb C): about 2-3% of people of African descent have haemoglobin C trait (one copy of the gene for Hb C). Haemoglobin C disease (seen in those with two copies of the gene) is rare and relatively mild. It usually causes a minor amount of haemolytic anaemia and a mild to moderate enlargement of the spleen.
    • Haemoglobin E (Hb E): this is one of the most common beta chain haemoglobin variants in the world. It is very prevalent in individuals of Southeast Asian descent. People who are homozygous for Hb E generally have a mild haemolytic anaemia, microcytic red blood cells, and a mild enlargement of the spleen. A single copy of the haemoglobin E gene does not cause symptoms unless it is combined with another mutation (e.g., a mutation causing beta thalassaemia).

    Some less common forms include:

    • Haemoglobin F (Hb F): this is the primary haemoglobin produced by a developing foetus. Normally, production of Hb F drops significantly after birth and decreases to adult levels by 1-2 years of age. Hb F may be elevated in several disorders, such as beta thalassaemia and sickle cell anaemia.
    • Haemoglobin H (Hb H): occurs in some cases of alpha thalassaemia. It is composed of four beta globin chains and is produced due to a severe shortage of alpha chains. Although each of the beta globin chains is normal, the four beta chains do not function normally.
    • Haemoglobin Barts: this type develops in foetuses with alpha thalassaemia. It is formed of four gamma protein chains when there is a shortage of alpha chains, in a manner similar to the formation of Hb H. Hb Barts disappears shortly after birth due to dwindling gamma chain production.

    Other types that may be identified include:

    • Haemoglobin D
    • Haemoglobin G
    • Haemoglobin J
    • Haemoglobin M
    • Haemoglobin Constant Spring

    A person can also inherit two different abnormal genes, one from each parent. This is known as being compound heterozygous or doubley heterozygous. Several different clinically significant combinations include haemoglobin SC disease, sickle cell – haemoglobin D disease, haemoglobin E – beta thalassaemia, and haemoglobin S – beta thalassaemia. For more on these, see the articles on Haemoglobin Abnormalities and Thalassaemia.

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

    Results Seen

    Condition

    Genes

    Slightly decreased Hb A
    Moderate amount Hb S (about 40%)

    Sickle cell trait

    One gene copy for Hb S (heterozygous

    Majority Hb S
    Increased Hb F (up to 10%)
    No Hb A

    Sickle cell disease

    Two gene copies for Hb S (homozygous)

    Majority Hb C
    No Hb A

    Haemoglobin C disease

    Two gene copies for Hb C (homozygous)

    Majority Hb A
    Some Hb H

    Haemoglobin H disease (alpha thalassaemia)

    Three out of four alpha genes are mutated (deleted)

    Majority Hb F
    Little or no Hb A

    Beta thalassemia major

    Both beta genes are mutated

    Majority Hb A
    Slightly Increased Hb A2 (4-8%)
    Hb F may be slightly increased

    Beta thalassemia minor

    One beta gene is mutated

  • Is there anything else I should know?

    Blood transfusions can interfere with haemoglobinopathy evaluation. A patient 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 haemoglobin has been given to reduce the risk of damage from sickling of red blood cells.

  • Why is every newborn screened for haemoglobinopathies?

    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 minimised if a condition is quickly identified and treated. Also, since newborn screening programs have mandated testing for haemoglobin 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.