Autoimmune hemolytic anemia (AIHA) is a rare autoimmune disease that affects approximately 1 or 2 in every 100,000 people each year. It is most common in females over the age of 40, but it can affect anyone of any age.

What Is AIHA?

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

Red blood cells are responsible for carrying oxygen from your lungs to the organs and tissues throughout your body. Some diseases, including AIHA, can reduce the number of RBCs and cause a health condition called anemia. People with anemia do not have enough RBCs to carry oxygen to their tissues, leading to a wide range of symptoms.

What Are the Types of AIHA?

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, and some infections are examples of other diseases that can cause secondary AIHA.

There are two distinct types of AIHA — warm autoimmune hemolytic anemia and cold AIHA. Warm and cold AIHA have different causes, primary symptoms, and treatments. Warm AIHA is more common than the cold-induced type and accounts for the majority of AIHA cases.

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 rare and affects 1 in every million people, with onset most often occurring between 40 and 80 years of age. Unlike warm AIHA and cold agglutinin disease, paroxysmal cold hemoglobinuria is most often seen in children and causes most childhood cases of autoimmune hemolytic anemia.

What Causes AIHA?

Most causes of primary AIHA are not known, but it is clear that AIHA involves the antibodies in the immune system. Your body has five types of antibodies — immunoglobulin (Ig) A, D, E, G, and M. Warm AIHA is caused by IgG antibodies binding to your red blood cells at normal body temperature. Cold agglutinin disease may occur when bulky IgM antibodies attack RBCs. Paroxysmal cold hemoglobinuria is caused by an IgG autoantibody called the Donath-Landsteiner antibody, which targets a group of sugars on the blood cells’ surface.

Many conditions can cause secondary AIHA, including:

• Genetic mutations, which may cause stem cells in bone marrow to produce defective RBCs, leading to a type of AIHA known as paroxysmal nocturnal hemoglobinuria
• Viral infections including 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 AIHA?

AIHA can cause a wide range of symptoms. Some people have “silent” disease and do not have any symptoms (asymptomatic). Many symptoms occur because people with AIHA do not have enough red blood cells to carry oxygen throughout their bodies. General symptoms of AIHA are similar to those of anemia, 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
• Dark urine
• Nausea or vomiting
• Diarrhea
• Fainting
• Confusion
• Enlarged spleen (splenomegaly)

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

How Is AIHA Diagnosed?

If you have symptoms of anemia, your health care provider will order blood tests to determine the cause. The direct antiglobulin test — also called the Coombs test — detects immunoglobulin or other immune components on the surface of red blood cells. This helps doctors determine the type of antibody that is causing the RBC destruction. Multiple tests may be needed to diagnose AIHA.

How Is AIHA Treated?

If your AIHA symptoms are mild, treatment may not be needed, and your health care provider may choose to closely monitor your red blood cell levels. One of the best approaches to managing secondary AIHA is to treat the condition that is causing your anemia.

If you are living with cold-induced AIHA, it is important that you 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 for people with AIHA when symptoms are more severe or the destruction of red blood cells is occurring rapidly. The treatment may depend on whether you have warm or cold AIHA. For example, corticosteroids are commonly prescribed to people living with warm AIHA, but their effectiveness is less clear in people with cold AIHA.

Rituximab is the first-line therapy for warm and cold AIHA. The medication targets the white blood cells (B cells) that create the autoantibodies responsible for destroying the red blood cells. Rituximab may be prescribed by itself or given with chemotherapy or immunosuppressive medications (drugs that reduce the immune system’s activity). If you have cold agglutinin disease, your doctor may also suggest sutimlimab-jome (Enjaymo), a treatment 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 are not responding to medications. Medical procedures for the treatment of AIHA include:

• Blood transfusion (giving blood or parts of blood through a vein)
• Plasmapheresis (removing antibodies from blood plasma)
• IV immunoglobulin (giving antibodies through a vein)
• Splenectomy (removing the spleen)
• Stem cell transplantation (replacing stem cells in bone marrow)

How Do Other Health Conditions Affect AIHA?

Many people with AIHA had other health conditions first. In many cases, it’s not clear how these disorders may be linked to or directly cause AIHA.

Having a comorbidity (more than one disease at a time) or an additional medical condition may make it harder for your health care team to diagnose or treat your AIHA, and it may even influence your prognosis. The following conditions may affect AIHA:

• Blood cancers — AIHA may be seen in people with leukemia, myeloma, or lymphoma.
• Other cancers — Although AIHA can also occur with solid tumors, treating the cancer with surgery or chemotherapy often cures AIHA. Cancer medications called immune checkpoint inhibitors can also uncommonly lead to AIHA.
• Autoimmune disorders — Many autoimmune diseases have been linked to 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 may lead to AIHA.
• Medications — In rare cases, certain antibiotics can lead to a type of AIHA called drug-induced immune hemolytic anemia.The most common drugs linked to this condition include penicillin, piperacillin, ceftriaxone, and cefotetan.

What Is the Prognosis for AIHA? 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.

Because AIHA can be fatal if it is not treated, it is important that you seek medical attention if you have symptoms of anemia.

Condition Guide

• What Are the Common Symptoms in People With AIHA?
• Exploring Autoimmune Hemolytic Anemia Treatment Options
• What Causes AIHA?
• What Are the Different Types of AIHA?
• How Is AIHA Diagnosed?
• Conditions Related to AIHA: What You Should Know