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Autoimmune Hemolytic Anemia


Evan M. Braunstein

, MD, PhD, Johns Hopkins University School of Medicine

Last full review/revision Apr 2021| Content last modified Apr 2021
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Autoimmune hemolytic anemia is a group of disorders characterized by a malfunction of the immune system that produces autoantibodies, which attack red blood cells as if they were substances foreign to the body.

  • Some people have no symptoms, and other people are tired, short of breath, and pale.

  • Severe disease may cause jaundice or abdominal discomfort and fullness due to splenomegaly (an enlarged spleen).

  • Blood tests are used to detect anemia and determine the cause of the autoimmune reaction.

  • Treatment is corticosteroids or other drugs that suppress the immune system and sometimes, splenectomy (surgical removal of the spleen).

(See also Overview of Anemia.)

Autoimmune hemolytic anemia is an uncommon group of disorders that can occur at any age. These disorders affect women more often than men. About half of the time, the cause of autoimmune hemolytic anemia cannot be determined (idiopathic autoimmune hemolytic anemia). Autoimmune hemolytic anemia can also be caused by or occur with another disorder, such as systemic lupus erythematosus (lupus) or a lymphoma, and it can be due to the use of certain drugs, such as penicillin.

Destruction of red blood cells by autoantibodies may occur suddenly, or it may develop gradually. If caused by a virus, the destruction may stop after a period of time. In other people, red blood cell destruction persists and becomes chronic. There are two main types of autoimmune hemolytic anemia:

  • Warm antibody hemolytic anemia: The autoantibodies attach to and destroy red blood cells at normal body temperature.

  • Cold antibody hemolytic anemia (cold agglutinin disease): The autoantibodies become most active and attack red blood cells only at temperatures well below normal body temperature.

Paroxysmal cold hemoglobinuria (Donath-Landsteiner syndrome) is a rare type of cold antibody hemolytic anemia. Destruction of red blood cells results from exposure to cold. Red blood cells may be destroyed even when cold exposure is limited to a small area of the body, such as when the person drinks cold water or washes hands in cold water. An antibody binds to red blood cells at low temperatures and causes destruction of red blood cells within arteries and veins after warming. It occurs most often after a viral illness or in otherwise healthy people, although it occurs in some people with syphilis. The severity and rapidity of development of the anemia varies.

Symptoms of Autoimmune Hemolytic Anemia

Some people with autoimmune hemolytic anemia may have no symptoms, especially when the destruction of red blood cells is mild and develops gradually. Others have symptoms similar to those that occur with other types of anemia (such as fatigue, weakness, and paleness), especially when the destruction is more severe or rapid.

Symptoms of severe or rapid destruction of red blood cells may include jaundice (yellowing of the skin and whites of the eyes), fever, chest pain, fainting, symptoms of heart failure (eg, shortness of breath), and even death. When destruction persists for a few months or longer, the spleen may enlarge, resulting in a sense of abdominal fullness and, occasionally, discomfort.

In people with cold antibody hemolytic anemia, the hands and feet may be cold or bluish.

When the cause of autoimmune hemolytic anemia is another disorder, symptoms of the underlying disorder, such as swollen and tender lymph nodes and fever, may dominate.

People with paroxysmal cold hemoglobinuria may have severe pain in the back and legs, headache, vomiting, and diarrhea. The urine may be dark brown.

Diagnosis of Autoimmune Hemolytic Anemia

  • Blood tests

Once blood tests show a person has anemia, doctors look for the cause. Doctors suspect increased destruction of red blood cells when a blood test shows an increase in the number of red blood cells that are immature (reticulocytes) or there is evidence of blood destruction on a blood smear (a test in which a drop of blood is spread on a slide and examined under a microscope). Alternatively, a blood test may show an increased amount of a substance called bilirubin produced by the destruction of red blood cells and a decreased amount of a protein called haptoglobin, which binds the hemoglobin released from the destroyed red cells.

Autoimmune hemolytic anemia as the cause is confirmed when blood tests detect increased amounts of certain antibodies, either attached to red blood cells (direct antiglobulin or direct Coombs test) or in the liquid portion of the blood (indirect antiglobulin or indirect Coombs test). Other tests sometimes help determine the cause of the autoimmune reaction that is destroying red blood cells.

Treatment of Autoimmune Hemolytic Anemia

  • Transfusion

  • Corticosteroids

  • Sometimes splenectomy

  • For paroxysmal cold hemoglobinuria, avoiding the cold

  • Sometimes immunosuppressants

When red blood cell destruction is severe, blood transfusions are needed. A blood transfusion should never be withheld for life-threatening anemia due to the presence of "incompatible" blood. However, transfusions do not treat the cause of the anemia and provide only temporary relief.

A corticosteroid such as prednisone is usually the first choice for treatment for warm autoimmune hemolytic anemia. High doses are used at first, followed by a gradual reduction of the dose over many weeks or months.

When people do not respond to corticosteroids or when the corticosteroid causes intolerable side effects, surgery to remove the spleen (splenectomy) is often the next treatment. The spleen is removed because it is the primary place where antibody-coated red blood cells are destroyed. When destruction of red blood cells persists after removal of the spleen or when surgery cannot be done, a drug called rituximab or immunosuppressants, such as cyclosporine, are used.

Cold hemolytic anemia is usually managed by avoidance of symptomatic triggers, or by treating the causative underlying disorder, such as lymphoma. In severe cases, plasmapheresis can be used to remove the offending antibody.

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