What Is Autoimmune Hemolytic Anemia?

Autoimmune hemolytic anemia (AIHA) is a rare red blood cell disorder that develops when there are not enough red blood cells (RBCs) because the body has destroyed them earlier than it should have. AIHA is also a type of anemia, a condition where a person lacks enough healthy RBCs to carry adequate levels of oxygen to the body's tissues.

With AHIA, the destruction occurs because the immune system is not working correctly, and mistakenly thinks red blood cells are foreign invaders and attacks them, causing them to die earlier and leaving a person without enough RBCs. AIHA is also called immune hemolytic anemia.

AIHA can affect both adults and children. It is much rarer in children and usually temporary. In adults, it is a long-term condition where a person experiences periods of remission (little or no symptoms) and periods of high disease activity. AIHA can either develop suddenly and quickly or gradually over time.

Autoimmune Hemolytic Anemia Symptoms

AIHA is classified as warm and cold. These have some common symptoms, but each also has specific symptoms. The warm and cold classifications are related to the type of antibodies involved.

Warm AIHA

Also called warm hemolysis, warm AIHA involves IgG antibodies. These antibodies bind RBCs at normal body temperature. Warm AIHA accounts for 75% to 80% of AIHA cases in adults.

With warm AIHA, symptoms will come on gradually over a period of weeks to months. In rare cases, they suddenly emerge over a period of a few days.

Symptoms may include:

• Pale or yellowish skin
• Fatigue
• Dizziness
• Heart palpitations
• Dark urine
• Chest pain

Cold AIHA

Also called cold agglutinin disease (CAD), cold AIHA displays IgM autoantibodies that bind RBCs when blood is exposed to cold temperatures—specifically 32 to 50 degrees Fahrenheit. Cold AIHA commonly affects adults in middle age or older.

Symptoms with cold AIHA are triggered by cold temperatures or viral infections and may include:

• Dizziness
• Fatigue
• Pale or yellow skin
• Cold hands and feet or Raynaud’s disease—a condition where some areas of the body feel numb and cold in certain circumstances
• Pain and/or blue coloring of the hands and feet
• Pain in the chest and the backs of the legs
• Vomiting
• Diarrhea
• Heart issues, including arrhythmia or a heart murmur

Causes

AIHA is a relatively rare disorder, with an estimated annual incidence of 1-3 cases per 100,000 per year. It is the result of the immune system not working properly and causing RBCs to die too early. Normally, RBCs would live in the body for 100 to 120 days. However, with AIHA—especially in severe cases—RBCs have a short lifespan of only a few days. 

AIHA may be primary or secondary. Primary AIHA, also called idiopathic, has no known underlying cause or mechanism of development. About 50% of the cases of AIHA are idiopathic­.

Anytime AIHA occurs as a complication of another disease, the term secondary is used. But the presence of another condition doesn’t automatically mean a person has secondary AIHA. Secondary AIHA is considered under certain circumstances including:

1. Secondary AIHA and the underlying condition occur together more often than alone
2. AIHA symptoms improve when the underlying, suspect condition is managed
3. The underlying condition causes the immune system to overact.

Causes of secondary AIHA may include:

• Exposure to certain toxins or chemicals, including medications
• Infections and viruses, including Epstein-Barr virus, cytomegalovirus or hepatitis
• Some types of blood cancer, including Non-Hodgkin’s lymphoma
• Autoimmune diseases, such as SLE lupus

Other causes of AIHA may include a combination of genetic and environmental influences. In a small number of cases, AIHA runs in families following an autosomal recessive pattern of inheritance—where a person doesn't display the disease unless they inherit the mutated genes from both parents.

Diagnosis

In making a diagnosis of AIHA, your healthcare provider will ask questions about your symptoms. They may then order bloodwork and urine tests to help in determining the cause of symptoms.

Testing may include:

Complete blood count (CBC): A complete blood count measures parts of the blood. It includes hemoglobin and hematocrit. Hemoglobin carries oxygen throughout the body and hematocrit shows how much space RBCs take up compared to other blood constituents. Low levels of both indicate anemia.

Urine hemoglobin test: A urine dipstick test will show positive for blood when RBCs are present or if they have broken down and the hemoglobin is passed in the urine.

Direct antiglobulin test (direct Coombs test): This test looks for increased antibodies attached to RBCs. A direct Coombs test may confirm a diagnosis of AIHA.

Reticulocyte test: The reticulocyte test measures the levels of reticulocytes, which are slightly immature red blood cells that have just been released from the bone marrow into the blood circulation. Reticulocyte levels will be higher if the bone marrow is responding to a loss of red blood cells due to bleeding or red blood cell destruction. If hemoglobin and hematocrit are low but reticulocytes are increased, it shows that the bone marrow is responding appropriately. If reticulocytes are low, it may indicate anemia is due to a problem with the bone marrow instead.

Bilirubin test: The bilirubin test measures the amount of bilirubin in the blood. Bilirubin is a breakdown product of the heme molecule in hemoglobin, and most of it in the blood comes from red blood cell destruction. High bilirubin levels can be a sign of hemolytic anemia, liver damage, or another disease.

Haptoglobin test: Haptoglobin is a protein produced by the liver whose role is to bind to any free hemoglobin in the blood and then allow it to be cleared and reprocessed. If haptoglobin levels are low, it shows that it is being used up to clear high levels of hemoglobin, as is seen in hemolytic anemia with the increased destruction of RBCs.

Cold agglutinins test: This test looks for high levels of certain antibodies linked to infections that cause AIHA. Determining whether a person has warm or cold agglutinins may help explain why AIHA might occur.

Treatment

If symptoms of AIHA are mild, treatment may not be needed. If a person is severely anemic, they may need a blood transfusion. However, a blood transfusion is only temporary and other treatments will be needed to keep symptoms managed.

If an underlying disease is the cause of AIHA, getting symptoms of that condition under control may resolve AIHA. If medications used to treat another condition are the cause (as in the case of drug-induced AIHA), stopping them or reducing dosages may resolve AIHA symptoms.

In adults, the immunosuppressant medication rituximab may be used in conjunction with corticosteroids for first-line treatment for AIHI. For both children and adults, rituximab is considered as part of initial treatment and as second-line treatment after glucocorticoids.

In 2022, the Food and Drug Administration (FDA) also approved Enjaymo (sutimlimab-jome) for use in adults with cold agglutinin disease (cold AIHA) to decrease the need for blood transfusions due to hemolysis.

IVIG (intravenous immunoglobulin) is also considered in conjunction with other therapies if initial therapies are ineffective. Though not a routine second-line treatment, splenectomy (surgical removal of the spleen) can be an effective treatment for warm AIHA.

A Word From Verywell

Some people find their AHIA will resolve completely without treatment. For other people, this is a long-term problem that may come and go for years. Your healthcare provider is the best position to answer questions about treatments that can give you the best outlook.

It is usually not possible to prevent AIHA, but healthcare providers monitor people who take certain medications or have certain health conditions. Severe cases of AIHA can make health conditions worse. Therefore, it is a good idea to get in touch with your healthcare provider if you think you are experiencing signs of AIHA.