Autoimmune hemolytic anemia (AIHA) is a rare autoimmune disease that affects about 1 or 2 in every 100,000 people each year. According to Cleveland Clinic, this condition is most common in females over age 40 but can affect anyone of any age.

What Is Autoimmune Hemolytic Anemia?

AIHA occurs when antibodies in the immune system mistakenly attack healthy red blood cells (RBCs) and cause them to die in a process known as hemolysis. This abnormal immune response destroys RBCs faster than new ones can be made.

Red blood cells are responsible for carrying oxygen from the lungs to other parts of the body, including organs and tissues. AIHA is a type of anemia — a condition in which the body doesn’t have enough red blood cells to supply adequate oxygen. This RBC shortage can lead to a variety of symptoms.

What Are the Types of Autoimmune Hemolytic Anemia?

AIHA can occur by itself with no underlying disease (primary or idiopathic AIHA) or be caused by other diseases (secondary AIHA). Blood cancers, autoimmune disorders, certain medications, and some infections are examples of other diseases that can cause secondary AIHA.

There are two distinct types of AIHA — warm autoimmune hemolytic anemia (warm AIHA) and cold autoimmune hemolytic anemia (cold AIHA).

Warm AIHA

Warm AIHA is more common than the cold-induced type and accounts for most AIHA cases. This condition is known as “warm” because antibodies attack red blood cells at normal body temperature.

Cold AIHA

Cold AIHA includes two types of hemolytic anemia — cold agglutinin disease and paroxysmal cold hemoglobinuria. These conditions are triggered when the antibodies bind to red blood cells at colder temperatures. Cold agglutinin disease is very rare, developing in only about 1 in every million people each year. It typically develops between ages 40 and 80. Unlike warm AIHA and cold agglutinin disease, paroxysmal cold hemoglobinuria is most often seen in children and causes most pediatric (childhood) cases of autoimmune hemolytic anemia.

What Causes Autoimmune Hemolytic Anemia?

Medical researchers don’t fully understand what causes primary AIHA. However, AIHA develops when certain immune system antibodies malfunction and start attacking red blood cells. When antibodies mistakenly target the body’s own cells, they’re sometimes called autoantibodies.

Your body has five types of antibodies — immunoglobulin (Ig) A, D, E, G, and M. Warm AIHA is caused by IgG antibodies binding to red blood cells. Cold agglutinin disease occurs when IgM antibodies attack RBCs. Paroxysmal cold hemoglobinuria is caused by an IgG antibody called the Donath-Landsteiner antibody, which targets a group of sugars on the surface of blood cells.

Many conditions can cause secondary AIHA, including:

• Viral infections such as Epstein-Barr virus, measles, mumps, rubella, chickenpox, cytomegalovirus, hepatitis, and HIV
• Cancers such as lymphoma, leukemia, and some solid tumors
• Autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, thyroid disease, Hashimoto’s disease, Sjögren’s syndrome, and ulcerative colitis
• Drug-induced hemolysis, a rare condition triggered by some medications, including antibiotics

What Are the Symptoms of Autoimmune Hemolytic Anemia?

AIHA can cause a wide range of symptoms. Some people have “silent” asymptomatic disease (no symptoms). Many symptoms occur because people with AIHA don’t have enough red blood cells to carry oxygen throughout their bodies. Symptoms of AIHA are similar to those of anemia in general, including:

• Low-grade fever
• Fatigue
• Lethargy (decreased alertness)
• Weakness or dizziness
• Heart palpitations (irregular heartbeat) or rapid heartbeat
• Shortness of breath or difficulty breathing
• Paleness
• Jaundice, which causes yellowing of the skin and the whites of your eyes
• Dark urine
• Nausea or vomiting
• Diarrhea
• Fainting
• Confusion
• Splenomegaly (enlarged spleen)

Some people with AIHA may experience symptoms such as headaches, as well as pain in their fingers or toes, chest, or muscles.

How Is Autoimmune Hemolytic Anemia Diagnosed?

If you have symptoms of anemia, your health care provider will order blood tests to find the cause. One key test, called a complete blood count, measures your levels of red and white blood cells, platelets, and hemoglobin (a protein that carries oxygen in blood).

The direct antiglobulin test — also called the Coombs test — detects antibodies on the surface of red blood cells. This helps doctors determine the type of antibody that’s causing the RBC destruction. Multiple tests may be needed to diagnose AIHA, including bilirubin testing, reticulocyte count, and lactate dehydrogenase (LDH) testing.

How Is Autoimmune Hemolytic Anemia Treated?

Mild AIHA symptoms might not need treatment, and your health care provider may choose to closely monitor your RBC levels. One of the best approaches to managing secondary AIHA is to treat the condition that’s causing your anemia.

If you’re living with cold-induced AIHA, it’s important to avoid the cold. If you must be in cold temperatures, protecting your head, face, hands, and feet can help reduce red blood cell hemolysis.

Medications are often prescribed when AIHA symptoms are more severe or red blood cells are being destroyed rapidly. Treatment may depend on whether you have warm or cold AIHA. For example, corticosteroids are commonly prescribed to people living with warm AIHA but aren’t considered effective for cold AIHA. If corticosteroids alone aren’t effective for treating warm AIHA — or in severe cases — rituximab may be recommended to help reduce immune system activity.

Rituximab (Rituxan) is the first-line therapy for cold AIHA when treatment is indicated. This medication targets the white blood cells (B cells) that create the autoantibodies responsible for destroying red blood cells. Rituximab may be prescribed by itself or with other medications for cold AIHA. If you have cold agglutinin disease, your doctor may also suggest sutimlimab-jome (Enjaymo), a treatment option that was approved in 2022 for this type of cold AIHA.

Your health care provider may recommend medical procedures if you have severe AIHA symptoms or aren’t responding to medications. Medical procedures for the treatment of AIHA include:

• Blood transfusion (receiving blood or blood components through a vein)
• Plasmapheresis, also known as plasma exchange (removing antibodies from blood plasma)
• IV immunoglobulin (receiving antibodies through a vein)
• Splenectomy (removing the spleen) in some cases of warm AIHA

Additionally, folic acid may be given as a supportive treatment to help your body produce new red blood cells.

How Do Other Health Conditions Affect Autoimmune Hemolytic Anemia?

Many people with AIHA have had related conditions that may have triggered AIHA. However, in many cases, the exact link between these disorders and AIHA isn’t fully understood.

Having a comorbidity (coinciding medical condition) may make it harder for your health care team to diagnose or treat your AIHA, which may influence your prognosis. The following conditions can affect AIHA:

• Blood cancers — AIHA may be seen in people with leukemia, myeloma, or lymphoma.
• Other cancers — Treating solid tumor cancers with surgery or chemotherapy often cures AIHA. Cancer medications called immune checkpoint inhibitors can cause AIHA in rare cases.
• Autoimmune disorders — Many autoimmune diseases can occur with AIHA. In these cases, AIHA is often treated with corticosteroids, splenectomy, or immunosuppressive medications.
• Infections — Rarely, viral infections increase the risk of AIHA. Bacterial infections such as pneumonia, tuberculosis, and brucellosis (a bacterial infection that spreads from animals to people) may lead to AIHA.
• Medications — Rarely, certain antibiotics such as penicillin, piperacillin, ceftriaxone, and cefotetan can lead to a type of AIHA called drug-induced immune hemolytic anemia.

AIHA has also been found to occur in 2 percent to 20 percent of allogeneic hematopoietic stem cell transplant (bone marrow transplant) cases.

What Is the Prognosis for Autoimmune Hemolytic Anemia? Can It Be Cured?

AIHA has a good prognosis when the condition is well managed with proper treatment. Approximately 20 percent to 30 percent of people living with AIHA require medication, surgery, or a blood transfusion, according to Cleveland Clinic. Additionally, some people with secondary AIHA are cured if the underlying condition is treated.

The prognosis of AIHA is especially good for people diagnosed before age 30. In a 2022 study, people under 30 who were diagnosed with primary AIHA had about the same life expectancy as the general population. However, the life expectancy of people diagnosed over age 30 was lower, with about 83 percent surviving 1 year and 65 percent surviving 5 years. Still, the average survival of people with AIHA has improved considerably in recent decades, rising from 8.2 years to 12.6 years.

AIHA may be more dangerous for older people because they’re more likely to develop comorbidities that can complicate AIHA or its treatment. For example, people with diabetes often have a worse prognosis for AIHA than people without diabetes.

Because AIHA can be fatal if it is not treated, it’s important that you seek medical attention if you have symptoms of anemia. Early diagnosis and treatment can help manage AIHA effectively, so don’t hesitate to reach out to a health care provider.

Find Your Team

MyAIHAteam is the social network for people with autoimmune hemolytic anemia and their loved ones. On myAIHAteam, more than 1,400 members come together to ask questions, give advice, and share their stories with others who understand life with AIHA.

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