How are they tested?
Laboratory testing for haemoglobin variants is an exploration of the microscopic appearance of the red blood cells (RBCs), an evaluation of the haemoglobin inside the RBCs, and an analysis of relevant gene mutations or deletions. Each test provides a piece of the puzzle, giving the clinician important information about which variants may be present. The tests that are ordered to search for haemoglobin variants are also used for thalassaemia workups. Searching for both is important because thalassaemia is sometimes inherited along with a haemoglobin variant.
FBC (full blood count). The FBC is a snapshot of the cells circulating in your bloodstream. Among other things, the FBC will tell the doctor how many red blood cells are present, how much haemoglobin is in them, and give the doctor an evaluation of the size of the red blood cells present. Mean corpuscular volume (MCV) is a measurement of the size of the red blood cells. A low MCV is often the first indication of thalassaemia. If the MCV is low and iron-deficiency has been ruled out, the person may be a thalassaemia trait carrier or have one of the haemoglobin variants that cause microcytosis (for example, Hb E).
A blood film (also called a peripheral smear or a manual differential when different types of white cells are counted). In this test, a doctor or laboratory scientist looks at a thin layer of blood, treated with a special stain, on a slide, under a microscope. The number and types of white blood cells, and appearance of red blood cells and platelets can be assessed and evaluated to see if they are normal. A variety of disorders affects normal blood cell production.
The red blood cells may b abnormal such as:
- microcytic (small)
- Hypochromic (pale)
- Vary in size (anisocytosis) or shape (poikilocytosis)
- Have a nucleus (abnormal in a mature red blood cell)
- Have an abnormal shape (e.g. “target cells” that look like a bull’s-eye under the microscope, or “stomatocytes” with slit-like grooves across the middle).
- Have abnormal texture such as “basophilic stippling” (blue dots in the cell, around the nucleus).
The greater the percentage of abnormal-looking red blood cells, the greater the likelihood of an underlying disorder and of impaired oxygen-carrying capability.
Haemoglobin variant testing. These tests identify the type, and measure the relative amount, of haemoglobins present in the red blood cells. Most of the common variants can be identified using one of these tests or a combination. The relative amounts of any variant haemoglobin detected can help diagnose combinations of haemoglobin variants and thalassaemia (compound heterozygotes).
DNA analysis. This test is used to investigate deletions and mutations in the alpha and beta globin-producing genes. Family studies can be done to evaluate carrier status and the types of mutations present in other family members. DNA testing is not routinely done but can be used to help diagnose haemoglobin variants, thalassaemia, and to determine carrier status.
Is any test preparation needed?
No test preparation is needed.
Why are they done?
Testing for haemoglobin variants is done to:
- Screen for common haemoglobin variants in newborns. This has become a standard part of newborn screening in the UK. Infants with variants such as HbS can benefit from early detection and treatment.
- Prenatal screening is also done in some areas on high-risk mothers: those with an ethnic background associated with a higher prevalence of haemoglobin variants (such as those of African descent) and those with affected family members. Screening may also be done in conjunction with genetic counselling prior to pregnancy to determine possible carrier status of parents.
- Identify variants in asymptomatic parents with an affected child.
- Identify haemoglobin variants in those with symptoms of unexplained anaemia, microcytosis, and/or hypochromasia. It may also be ordered as part of an anaemia investigation.