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Autoimmune hemolytic anemia (AIHA), also known as immune hemolytic anemia, is a condition in which a person’s own immune system attacks their red blood cells. Although AIHA is potentially fatal, it can be managed if it’s properly diagnosed. The condition is generally diagnosed through a series of blood tests.
In this article, we’ll look at the various tests used to diagnose AIHA and what those tests tell your doctor.
AIHA is an autoimmune disorder in which your immune system creates antibodies that attack your red blood cells, resulting in cell death (hemolysis). Antibodies are proteins that attack foreign substances in the body. When the immune system produces an antibody that targets a person’s own proteins — as with AIHA and other autoimmune conditions — it’s called an autoantibody.
As you lose red blood cells, you develop a condition known as anemia. Anemia occurs when your body doesn’t have enough red blood cells to carry oxygen throughout your body.
AIHA can occur by itself, with no other obvious disease. This is called primary, or idiopathic, AIHA. AIHA can also be linked with other conditions, known as secondary AIHA. Secondary AIHA is commonly associated with cancers — such as lymphoma and leukemia — as well as other autoimmune diseases, including systemic lupus erythematosus (lupus).
There are two main types of AIHA: warm autoimmune hemolytic anemia and cold autoimmune hemolytic anemia. With warm AIHA, immunoglobulin G (or IgG) antibodies bind your red blood cells at your normal body temperature. In cold AIHA, immunoglobulin M (or IgM) antibodies attack your red blood cells at slightly colder temperatures.
Each person experiences AIHA differently. Common symptoms of AIHA that may lead your doctor to suspect you have it include:
Numerous tests can help with diagnosing AIHA. Many diagnostic tests look for the presence of dying cells, autoantibodies, or low cell counts in the blood, all signs of an autoimmune blood disorder.
The following tests are performed by collecting blood samples through simple blood draws, typically from your arm.
The complete blood count (CBC) is a basic blood test your health care provider can perform. This test measures several different factors in your blood including:
The CBC is a general blood test that will first alert your doctor to your anemic condition. It’s usually not a definitive test for AIHA, and your doctor likely will follow up with additional tests to fully diagnose the illness.
The peripheral smear, similar to the CBC, uses a blood sample to look at the number and types of cells in your blood. A laboratory specialist will place your blood on a piece of glass and look at your cells under the microscope. They’ll observe the size, shape, and number of cells in a smear to help determine if you have AIHA.
The presence of spherocytes in your sample may indicate AIHA. Spherocytes are red blood cells that are more spherical and slightly smaller than normal red blood cells.
Reticulocytes are slightly underdeveloped red blood cells. As your body becomes anemic, it tries to compensate by sending out more red blood cells, even if they aren’t fully mature yet. Counting the number of reticulocytes in your blood can help your doctor determine anemic conditions.
Normally, reticulocytes will make up anywhere from 0.5 percent to 2.5 percent of your blood. However, people experiencing anemia can sometimes have this value exceed 4 percent. Talk to your doctor or hematology specialist about what your test results mean. Different labs may have slightly different normal ranges.
Bilirubin is a yellowish compound that is normally found in bile and is the product of breaking down red blood cells. The bilirubin test measures levels of bilirubin in your blood.
Elevated levels of bilirubin can indicate red blood cell death, liver problems, or a benign condition known as Gilbert’s syndrome. This test would be used in addition to other tests to confirm AIHA.
Autoantibodies in the blood could also be a sign of AIHA. The Coombs test checks your blood for antibodies that target your red blood cells. There are two types of the Coombs test — direct and indirect. The direct Coombs test — also known as the direct antiglobulin test — is used to diagnose AIHA. It works by checking to see if your red blood cells have antibodies attached to them.
The indirect test is used for blood transfusion and prenatal testing.
The Coombs test can also help distinguish between warm and cold AIHA based on what types of proteins are found on the red blood cells.
Lactate dehydrogenase (LDH) is a protein found in nearly every cell and tissue in the body. Normally, LDH is kept within the cell. However, if the cell is damaged or dies, the LDH is released and can circulate in your bloodstream. The LDH test measures LDH levels in your blood. High levels can indicate disease, but the test won’t tell your doctor where the LDH came from.
Your health care provider may order a secondary LDH test known as an LDH isoenzymes test. There are five forms of LDH, known as isoenzymes, which are found in different cell types and tissues. The isoenzymes test can tell which version of LDH is elevated in the blood, and hence where the damage might be coming from.
LDH-1 is the main form of LDH found in red blood cells. Healthy individuals have more LDH-2 in their blood than LDH-1. When severe anemia occurs, LDH-1 values can become higher than LDH-2 values. Seeing more LDH-1 in your blood than LDH-2 will tell your doctor that you’re experiencing loss of red blood cells.
The haptoglobin test measures levels of haptoglobin in your blood. Haptoglobin is a protein produced in the liver that binds to hemoglobin. As your red blood cells die, they release their hemoglobin. The haptoglobin binds the loose hemoglobin, and the bound proteins are removed from your blood through your liver.
In a person with AIHA, the haptoglobin test would reveal lower-than-normal levels of haptoglobin.
The cold agglutinin titer is a diagnostic test used to determine how many autoantibodies are present in someone with cold AIHA. For this test, plasma — the portion of blood containing antibodies — is separated from the rest of your blood. The plasma is then diluted and mixed with red blood cells. As the autoantibodies attack the red blood cells, they clump together. The more autoantibodies present, the more your plasma needs to be diluted before you stop seeing cell clumping.
Diagnosing AIHA is a complex process, requiring a doctor to look for various signs to rule out potential causes. Each of the aforementioned tests provides some information that helps your doctor hone in on the cause of your symptoms.
To summarize the tests and what they reveal:
This may seem like many steps to discover your AIHA status, but they’re necessary to get a proper diagnosis. Fortunately, your doctor may run some of these tests at the same time, meaning fewer visits and blood draws. Although you may feel discomfort at the time of the blood draw, once you give your sample, you’re usually free to resume normal activities.
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Todd Gersten, M.D.
is a hematologist-oncologist at the Florida Cancer Specialists & Research Institute in Wellington, Florida. Review provided by VeriMed Healthcare Network.
Learn more about him here.
Brian Niemeyer, Ph.D.
received his doctorate in immunology from University of Colorado Anschutz Medical Campus..
Learn more about him here.
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