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Blood Tests for AIHA: What Do They Show?

Posted on August 04, 2022
Medically reviewed by
Richard LoCicero, M.D.
Article written by
Caroline Wallace, Ph.D.

Many blood tests are used to diagnose the rare autoimmune disease autoimmune hemolytic anemia (AIHA). If you are newly diagnosed or living with AIHA, you may wonder what the different blood test results indicate about your condition. This article will help you better understand these test results and your health care provider’s explanations.

Understanding the Biology Behind AIHA

AIHA occurs when your immune system creates antibodies that attack your red blood cells (RBCs), causing them to die prematurely in a process known as hemolysis. When this occurs, your RBCs are destroyed faster than they can be made.

Red blood cells (also called erythrocytes) contain a molecule called hemoglobin, which carries oxygen molecules to all the cells and organs in your body. RBCs develop in the bone marrow (the soft tissue in the middle of your bones) and then circulate in the blood for an average of 120 days before they are destroyed in the spleen or the liver. Normal RBCs are the shape of a donut — they are round, flat discs with an indention in the center.

Because AIHA reduces the number of red blood cells in the blood, there are not enough cells to transport oxygen throughout your body. This causes symptoms of anemia, including fatigue, shortness of breath, paleness, irregular heartbeat, and jaundice (yellowing of the skin).

To understand the blood tests for AIHA, a person must first understand the basics of the immune system. Your body makes five types of antibodies — immunoglobulin (Ig) A, IgD, IgE, IgG, and IgG — to detect and fight pathogens in your body. When antibodies detect a person’s cells instead of foreign bacteria or viruses, the antibodies are called autoantibodies. The presence of autoantibodies can lead to diseases such as AIHA because they damage a person’s tissues and organs.

Warm Autoimmune Hemolytic Anemia

Warm AIHA accounts for 60 percent to 70 percent of all AIHA cases. This type of AIHA is called warm because the autoantibodies trigger RBC hemolysis at body temperature. Most cases of warm AIHA are caused by IgG autoantibodies. Rarely, warm AIHA can be caused by IgM or IgA autoantibodies.

Cold Autoimmune Hemolytic Anemia

There are two primary subsets of cold AIHA — cold agglutinin disease (CAD) and paroxysmal cold hemoglobinuria (PCH). CAD involves IgM antibodies that cause the red blood cells to clump together. The immune system “sees” a mass of RBCs as foreign or abnormal, which triggers the destruction of the clumped RBCs. PCH is generally seen in children and is associated with viral infections. A specific IgG antibody called the Donath-Landsteiner autoantibody binds to RBCs and triggers hemolysis.

Blood Tests for AIHA

Your doctor uses blood tests to diagnose and monitor your AIHA. Although it may seem like many separate tests are required, many tests can be run at the same time with a single blood draw. Your hematologist (blood specialist) can monitor your disease and modify any treatments by comparing the results of your new blood work with your past blood work results.

Doctors must be like detectives to determine what is causing a person’s symptoms. Diagnosing AIHA requires ruling out other possible health conditions. When a person has symptoms of anemia, the health care provider will first determine if the person has a low number of red blood cells.

Complete Blood Count

The complete blood count (CBC) is a general blood test that measures the amounts of the different types of cells in your blood, including:

  • Red blood cells, which carry oxygen
  • White blood cells, which are immune cells
  • Platelets, which help your blood clot
  • Hemoglobin, the oxygen-carrying molecule in RBCs
  • Hematocrit, the number of RBCs in relation to the fluid component (plasma) of your blood

Healthy adult men normally have 4.35 to 5.65 million cells per microliter of blood, and adult women typically have 3.92 to 5.13 million cells per microliter of blood. If the CBC results show a low number of RBCs, it indicates that a person is anemic.

Peripheral Blood Smear

The peripheral blood smear test also looks at the number and types of cells in your blood, but it provides a visual look as well. A laboratory technician uses a microscope to look at the size, shape, and number of cells in your blood to help determine if your anemia is AIHA. If smaller and rounder RBCs, called spherocytes, are seen, a person has either AIHA or another condition called hereditary spherocytosis.

If the first two blood tests indicate anemia, your doctor will need to determine the cause. Anemia may be caused by various issues, including bleeding, iron deficiency, or vitamin B deficiency. The following tests help determine if red blood cell death is causing the anemia.

Lactate Dehydrogenase Test

The lactate dehydrogenase (LDH) test measures the amount of LDH in your blood. LDH is a type of protein (enzyme) released when cells are damaged. High LDH levels indicate that cells are being destroyed. A more specific test called an LDH isoenzyme test measures the amount of the five different types of LDH. LDH-1 is the main type of LDH in red blood cells. Severe anemia that is caused by red blood cell death causes LDH-1 values to become elevated.

Haptoglobin Test

The haptoglobin test measures the amount of haptoglobin — a protein made by your liver — in your blood. The function of haptoglobin is to bind to the small amount of hemoglobin outside the RBCs circulating in your blood. The haptoglobin attaches to the hemoglobin, and this compound is removed by the liver. Hemolytic anemia, such as AIHA, increases the amount of hemoglobin outside the RBCs when the cells are destroyed. An increased amount of haptoglobin is needed to bind to the excess hemoglobin so it can be cleared from the blood. This causes low haptoglobin levels in your blood.

Reticulocyte Count

Reticulocytes are red blood cells that are still developing (immature RBCs). A reticulocyte count measures the number of reticulocytes in the blood. Usually, the percentage of reticulocytes in a healthy person is 0.5 percent to 2.5 percent. People with anemia often have a higher percentage of reticulocytes. This is because the body tries to compensate for the hemolysis of the mature RBCs by releasing more immature reticulocytes into the blood.

Bilirubin Test

Bilirubin is a brownish-yellow substance made during the normal breakdown of RBCs. The bilirubin test measures the amount of bilirubin in your blood. If the results show high bilirubin levels, that may indicate liver or bile duct problems or that red blood cell death is occurring. The results of this test, in combination with the other three tests, can indicate that RBC hemolysis is causing a person’s anemia.

Coombs Test

The Coombs test determines if autoantibodies are causing the RBC death. There are two types of the Coombs test — direct and indirect. The direct Coombs test (also called the direct antiglobulin test) detects if antibodies are stuck directly on the surface of RBCs in your blood. The direct Coombs test can determine which type of autoantibody (IgM, IgA, IgG) is attached to the RBCs, which suggests either warm or cold AIHA depending on the result.

The indirect Coombs test, which determines if antibodies against RBCs are circulating in the blood, is generally used to check for blood transfusion reactions and prenatal testing.

Cold Agglutinin Titer

This test measures how many autoantibodies are present in a person with cold AIHA. The cold agglutinin titer test is done to determine how much cold agglutinin (autoantibodies) is present, so your doctor can see how that level changes with treatment. This test separates a person’s serum — the liquid part of the blood — from the RBCs. The plasma is then diluted and mixed with the person’s RBCs. The autoantibodies present in the serum cause the RBCs to clump together. The more autoantibodies present, the more dilution is required before the RBCs stop clumping together.

Find Your Team

On myAIHAteam, you have access to a social network for people with autoimmune hemolytic anemia and their loved ones. Join to connect with others who understand life with a rare blood disorder.

Have you been recently diagnosed with AIHA? Share your experience in the comments below, or start a conversation by posting on myAIHAteam.

All updates must be accompanied by text or a picture.
Richard LoCicero, M.D. has a private practice specializing in hematology and medical oncology at the Longstreet Clinic Cancer Center, in Gainesville, Georgia. Review provided by VeriMed Healthcare Network. Learn more about him here.
Caroline Wallace, Ph.D. has a doctorate in biomedical science from the Medical University of South Carolina. Learn more about her here.

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