Autoimmune hemolytic anemia (AIHA) is a form of anemia that is commonly associated with CLL. It is estimated that 10% to 20% of CLL patients may develop AIHA sometime during the course of their illness. The development of this condition does not have implications for the staging of CLL; rather, it is usually reported as a complication of progressing disease.

In AIHA, the immune system malfunctions and develops anitbodies against the patient's own red blood cells and destroys them prematurely. Symptoms of AIHA include nosebleeds, bleeding gums, chills, fatigue, pallor, shortness of breath, rapid heart rate, jaundice, and swelling of the spleen (splenomegaly). Diagnosis is confirmed with a test called the direct antiglobulin test or Coombs test. The mainstay treatment of AIHA associated with CLL is prednisone. Some forms of AIHA are treated by splenectomy because the spleen destroys antibody-coated, red blood cells. Removing the spleen allows the antibody-coated cells to function longer.

AIHA is not the only form of anemia that occurs in CLL patients. Anemia can also occur as a result of chemotherapy, due to blood loss, and in advanced CLL when malignant lymphocytes compromise the production of normal blood cells. Other forms of anemia can also occur, but these are the most common reasons for anemia in CLL patients.