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.

What Is AIHA?

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, which is 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).

Symptoms and Types of AIHA

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:

• Dizziness
• Fatigue
• Fever
• Fast or irregular heartbeat
• Shortness of breath and difficulty breathing
• Jaundice (yellowing of the skin or eyes)
• Headaches
• Muscle pain
• Diarrhea

Who Diagnoses AIHA?

Your primary care provider may be the first person you discuss your symptoms with. They may be the one to diagnose your AIHA, or they may refer you to a blood specialist called a hematologist.

Health History and Physical Examination

Before ordering any tests, your doctor will ask you several questions about your personal health history. They may also ask about your family’s health history and conduct a physical exam.

Questions about a family history of anemia or medications you may be taking can help your doctor understand what could cause your symptoms and what tests are appropriate. Your doctor will also likely ask you about any other health conditions you have, since illnesses like lupus can lead to AIHA.

After taking a detailed medical history, your doctor may do a physical exam to check for certain AIHA symptoms like jaundice or an irregular heartbeat.

At this point, your doctor will likely order blood work to confirm whether you are anemic and to help determine the cause.

Tests for Diagnosing AIHA

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.

Complete Blood Count

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:

• Red blood cells — Cells that carry oxygen throughout your body
• Hemoglobin — Protein your red blood cells use to carry oxygen
• White blood cells — Cells that make up your immune system and fight infections
• Hematocrit — The ratio of red blood cells to the volume of blood
• Platelets — Small blood cells that help your blood clot

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.

Peripheral Smear

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.

Reticulocyte Count

Reticulocytes are precursors to mature 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 Test

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 (as red blood cells break open and release their contents into the bloodstream). Bilirubin can also be a sign of liver problems or a benign condition known as Gilbert’s syndrome. This test would be used in addition to other tests to confirm AIHA.

Coombs Test

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, and it tests for the presence of antibodies in the blood directed against red blood cells.

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 Test

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 a loss of red blood cells.

Haptoglobin Test

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.

Cold Agglutinin Titer

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.

Why Are So Many Tests Necessary To Diagnose AIHA?

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:

• A CBC or peripheral smear detects anemia.
• LDH, haptoglobin, and bilirubin tests identify red blood cell death as the cause of anemia.
• The Coombs test can reveal that autoantibodies are the cause of red blood cell death.
• The Coombs test and cold agglutinin titer for antibody levels can determine whether you have warm or cold AIHA.

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.

Find Your Team

On myAIHAteam, you’ll meet other people with AIHA, as well as their loved ones. Here, members who understand life with AIHA come together to share support, advice, and stories from their daily lives.

Have you been diagnosed with AIHA? What tests did your care team use for your AIHA diagnosis? Share your experiences and thoughts in the comments below or by posting on myAIHAteam.