Testing for hemoglobin abnormalities (variants) is done:
- To screen for common and clinically significant hemoglobin variants in newborns. In all states, this has become a standard part of newborn screening. Infants with variants such as Hb S can benefit from early detection and treatment.
- As part of prenatal screening, on high-risk women including those with an ethnic background associated with a higher prevalence of hemoglobin variants (such as those of African descent) and those with affected family members. Screening may also be done in conjunction with genetic counseling prior to pregnancy to determine possible carrier status of potential parents.
- To identify variants in asymptomatic parents with an affected child.
- To identify hemoglobin variants in those with symptoms of unexplained anemia, with red blood cells (RBCs) that are small and/or paler than normal (microcytosis and hypochromia). It may also be ordered as part of an anemia investigation.
Laboratory testing for hemoglobin variants is an exploration of the "normalness" of an individual's red blood cells, an evaluation of the hemoglobin inside the RBCs, and/or an analysis of relevant gene mutations. Each test provides a piece of the puzzle, giving the clinician important information about the hemoglobins that may be present. Testing typically includes:
- CBC (complete blood count): The CBC is a snapshot of the cells circulating in the blood. Among other things, the CBC will tell the doctor how many red blood cells are present, how much hemoglobin is in them, and give the doctor an evaluation of the average 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 thalassemia. If the MCV is low and iron-deficiency has been ruled out, the person may be a carrier of the thalassemia trait or have a hemoglobin variant that results in smaller than normal RBCs (for example, Hb E).
- Blood smear (also called a peripheral smear): In this test, a trained laboratorian looks under the microscope at a thin layer of blood on a slide treated with a special stain. The number and type of white blood cells, red blood cells, and platelets can be evaluated to see if they are normal and mature. With a hemoglobinopathy, the red blood cells may be:
- Smaller than normal (microcytic)
- Paler than normal (hypochromic)
- Varying in size (anisocytosis) and shape (poikilocytosis, e.g., sickle-shaped cells)
- Having a nucleus (nucleated red blood cell, not normal in a mature RBC) or crystal (e.g., C crystal)
- Having uneven hemoglobin distribution (producing "target cells" that look like a bull's-eye under the microscope).
The greater the percentage of abnormal-looking red blood cells, the greater the likelihood of an underlying disorder.
- Hemoglobinopathy evaluation: These tests identify the type, and measure the relative amount, of the different types of hemoglobin present in an individual's 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 hemoglobin detected can help diagnose combinations of hemoglobin variants and thalassemia (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 confirm hemoglobin variants, thalassemia, and to determine carrier status.