Possible causes include:

• Certain chemicals, medicines, and toxins
• Infections
• Transfusion of blood from a donor with a blood type that does not match
• Certain cancers

When antibodies form against red blood cells for no reason, the condition is called idiopathic autoimmune hemolytic anemia.

The antibodies may also be caused by:

• A complication of another disease
• Past blood transfusions
• Pregnancy (if the baby's blood type is different from the mother's)

Risk factors are related to the causes.

You may not have symptoms if the anemia is mild. If the problem develops slowly, symptoms that may occur first include:

• Feeling weak or tired more often than usual, or with exercise
• Headaches
• Problems concentrating or thinking

If the anemia gets worse, symptoms may include:

• Lightheadedness when you stand up
• Pale skin color (pallor)
• Shortness of breath
• Sore tongue

You may need the following tests:

• Absolute reticulocyte count
• Direct or indirect Coombs test
• Hemoglobin in the urine
• LDH (level of this enzyme rises as a result of tissue damage)
• Red blood cell count (RBC), hemoglobin, and hematocrit
• Serum bilirubin level
• Serum haptoglobin
• Donath-Landsteiner test
• Cold agglutinins
• Platelet count
• Protein electrophoresis - serum
• Pyruvate kinase

The first treatment tried is most often a steroid medicine, such as prednisone. If a steroid medicine does not improve the condition, treatment with intravenous immunoglobulin (IVIG) or removal of the spleen (splenectomy) may be considered.

You may receive treatment to suppress your immune system if you do not respond to steroids. Medicines such as azathioprine (Imuran), cyclophosphamide (Cytoxan), and rituximab (Rituxan) have been used.

Blood transfusions are given with caution, because the blood may not be compatible and it may cause more red blood cell destruction.

The disease may start quickly and be very serious, or it may stay mild and not need special treatment.

In most people, steroids or splenectomy can totally or partially control anemia.

Severe anemia rarely leads to death. Severe infection may occur as a complication of treatment with steroids, other medicines that suppress the immune system, or splenectomy. These treatments impair the body's ability to fight infection.

Contact your health care provider if you have unexplained fatigue or chest pain, or signs of infection.

Screening for antibodies in donated blood and in the recipient may prevent hemolytic anemia related to blood transfusions.

Anemia - immune hemolytic; Autoimmune hemolytic anemia (AIHA)

Michel M. Autoimmune and intravascular hemolytic anemias. In: Goldman L, Cooney KA, eds. Goldman-Cecil Medicine. 27th ed. Philadelphia, PA: Elsevier; 2024:chap 146.

Michel M, Jäger U. Autoimmune hemolytic anemia. In: Hoffman R, Benz EJ, Silberstein LE, et al, eds. Hematology: Basic Principles and Practice. 8th ed. Philadelphia, PA: Elsevier; 2023:chap 47.

Wong E, Rose MG, Berliner N. Disorders of red blood cells. In: Wing EJ, Schiffman FJ, eds. Cecil Essentials of Medicine. 10th ed. Philadelphia, PA: Elsevier; 2022:chap 48.

Updated by: Todd Gersten, MD, Hematology/Oncology, Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by VeriMed Healthcare Network. Also reviewed by David C. Dugdale, MD, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.