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Autoimmune hemolytic anemia (AIHA) is a rare disease with multiple types and even subtypes. AIHA is an autoimmune disease, which means that your immune system creates antibodies that target your cells (autoantibodies).
In AIHA, autoantibodies attack red blood cells, causing them to die in a process known as hemolysis. The loss of red blood cells results in anemia, a condition in which you no longer have enough red blood cells to carry oxygen to your tissues.
AIHA can cause a wide range of symptoms, including:
When AIHA occurs by itself, with no underlying disease, it is called primary or idiopathic AIHA. If AIHA is caused by other diseases, it is known as secondary AIHA. Lymphomas, leukemias, and autoimmune disorders, such as systemic lupus erythematosus (lupus), can lead to secondary AIHA.
There are two distinct types of AIHA — warm and cold — which differ in their causes, primary symptoms, and treatments.
The most common form of the disease, warm AIHA, accounts for 60 percent to 70 percent of all AIHA cases. The disorder affects 1 to 3 people per every 100,000 each year and can start at any age. However, it is more common in adults than children and usually occurs between ages 50 and 70.
Normally, to fight off infections, your body will make five types of antibodies — immunoglobulin (Ig) A, IgD, IgE, IgM, and IgG. With warm AIHA, IgG antibodies are primarily responsible for red blood cell death. These autoantibodies are also called warm antibodies because they are most active at your core body temperature, leading to the name warm AIHA.
Some symptoms of AIHA are more commonly found in people with the warm form of the disease. Symptoms associated with warm AIHA include:
Cold-induced AIHA encompasses two forms of hemolytic anemia — cold agglutinin disease (CAD) and paroxysmal cold hemoglobinuria (PCH). As the name implies, many of the symptoms are triggered in cold temperatures. The antibodies responsible for these disorders are also called cold antibodies because they bind to red blood cells at colder temperatures.
Beyond the general symptoms of AIHA, people with cold AIHA may also experience the following:
CAD affects 1 out of every million people, with onset most often occurring between 40 and 80 years of age. People with certain diseases have a higher risk of developing secondary cold agglutinin disease. These conditions include:
Cold agglutinin disease involves IgM antibodies, which cause red blood cells to clump up. This clumping triggers immune responses that end up destroying the red blood cells.
Unlike warm AIHA and cold agglutinin disease, paroxysmal cold hemoglobinuria is most often seen in children, among whom it is the most common cause of AIHA. Although historically PCH has been classified as a cold AIHA, recent cases have shown that antibody binding and red blood cell death can also occur in warmer temperatures.
In children, PCH is strongly associated with viral infections and often resolves on its own after the virus clears. A specific IgG antibody, the Donath-Landsteiner autoantibody, is produced in response to viral infections. This antibody binds to red blood cells and triggers hemolysis.
Because of the viral infection, children who experience paroxysmal cold hemoglobinuria often have flu-like symptoms — but no signs of anemia — for one to two weeks. After that period, symptoms of anemia that are typical for AIHA will start to appear.
Defective bone marrow stem cells cause paroxysmal nocturnal hemoglobinuria (PNH). Stem cells are responsible for making all types of cells in your body, including blood cells. With PNH, the body creates red blood cells that are more susceptible to destruction by the immune system.
For PNH to develop, a genetic mutation must occur in the PIGA gene of your blood stem cells. The protein made by this gene sits on the cells’ surface and protects them from your immune system. Mutations in the PIGA gene result in the loss of the protein, which leaves your cells exposed to attacks from a specialized part of your immune system known as complement.
This form of hemolytic anemia often starts when people are in their 30s and 40s. In the U.S., an estimated 400 to 500 new cases are diagnosed each year.
People with PNH will often display only some of a wide range of possible symptoms. The symptoms of PNH include:
AIHA is a highly manageable disorder. If you have secondary AIHA, it is crucial to treat its underlying condition. Treatment for autoimmune hemolytic anemia can include medications, surgery, and blood transfusions. The precise regimen can vary depending on the type of AIHA you have.
For people with warm AIHA, first-line treatment may consist of medications aimed at suppressing the immune system. Corticosteroids such as prednisone can help with this. The drug rituximab can also be used to reduce the production of autoantibodies. If people do not respond to rituximab, their health care provider may recommend surgery to remove their spleen (splenectomy).
As with warm AIHA, people with cold agglutinin disease may find relief using immunosuppressive treatments such as rituximab. Your doctor may also suggest sutimlimab-jome (Enjaymo), a treatment for CAD that was approved in 2022. However, because hemolysis can be linked with temperature, avoiding the cold may also help manage CAD.
Most cases of paroxysmal cold hemoglobinuria will clear up without specific treatment. If the anemia is severe enough, transfusions of red blood cells may help. Beyond this, only supportive measures such as bed rest and warmth are required for PCH.
Paroxysmal nocturnal hemoglobinuria treatment includes medications to suppress the immune system by blocking activation of complement. Blood transfusions may be required in cases of severe anemia. Because PNH is associated with a higher risk of blood clots, blood thinners may be prescribed as well.
Condition Guide
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.
