The autoimmune hemolytic anemias are rare disorders characterized by the premature destruction (hemolysis) of red blood cells at a rate faster than they can be replaced. Acquired hemolytic anemias are non-genetic in origin. Idiopathic acquired autoimmune diseases occur when the body's natural defenses against invading organisms (e.g., lymphocytes, antibodies) destroy its own healthy tissues for no known reason. Normally, the red blood cells (erythrocytes) have a life span of approximately 120 days before being removed by the spleen. The severity of this type of anemia is determined by the life span of the red blood cell and by the rate at which these cells are replaced by the bone marrow.
Clinicians are able to determine quite accurately (Coombs test) whether or not red blood cells are carrying with them chemicals that are being incorrectly recognized as an "enemy" and therefore subject to autoimmune destruction.
Acquired autoimmune hemolytic anemia is a disorder that occurs in individuals who previously had a normal red blood cell system. The disorder may occur as the result of, or in conjunction with, some other medical condition, in which case it is "secondary" to another disorder. Less commonly, it occurs alone without a precipitating factor.
Acquired autoimmune hemolytic anemia occurs in different forms, including warm antibody hemolytic anemia and cold antibody hemolytic anemia.
In warm antibody hemolytic anemia, the self-generated antibodies (autoantibodies) attach themselves and cause the destruction of the red blood cells at temperatures above normal body temperature. In contrast, in the cases of cold antibody hemolytic anemia, the self-generated antibodies (autoantibodies) attach themselves and cause the destruction of the red blood cells at temperatures below normal body temperature. (For more information on this disorder, choose "Warm Antibody Hemolytic Anemia" and/or Cold Antibody Hemolytic Anemia as your search term in the Rare Disease Database.)
Generally symptoms of acquired autoimmune hemolytic anemia resemble those of other anemias and may include fatigue, pale color, rapid heartbeat, shortness of breath, dark urine, chills, and backache. In severe cases, yellow skin color (jaundice) may be present and the spleen may be enlarged.
If the autoimmune hemolytic anemia is secondary to another cause, the symptoms of the other cause may be most apparent.
Hemolytic anemia may be caused by any one or more of several kinds of disorders. For example, contributing factors may include:
An autoimmune response in which the patient’s own immune system destroys the patient’s red blood cells. The disorder is more common among people who already have an autoimmune disorder such as lupus.
The taking of certain types of medication by certain people. Among such medications are penicillin, quinine, methyldopa, and sulfonamides.
Inherited enzyme deficiencies inside red blood cells that may cause the cells to become fragile and subject to destruction. Most commonly, low levels of the enzymes pyruvate kinase or glucose-6-phosphate dehydrogenase are the culprits.
Hemoglobin disorders such as sickle cell anemia or one of the thalassemias (blood disorders that affect the cells ability to produce hemoglobin).
Abnormalities of the cell membrane that cause the red blood cells to take on a shape other than the normal disc-shape. Such red blood cells may show up as spheres or ellipses or cup-like.
Some unusual situations may lead to the destruction of red blood cells. For example, as the cells pass through oxygenating machines during open-heart surgery, they may undergo changes that lead to hemolytic anemia.
When acquired autoimmune hemolytic anemia occurs from unknown causes, it affects twice as many women as men, specifically women under 50 years old. Cold antibody hemolytic anemia most commonly affects elderly persons, and warm antibody hemolytic anemia can affect anyone at any age.
Upon suspicion of hemolytic anemia, blood will be tested to determine the proportion of immature red blood cells to mature ones. If the ratio is high, hemolytic anemia is likely. Another blood test (Coombs test) is used to determine whether the amount of certain antibodies is higher than normal. If so, the diagnosis may be autoimmune hemolytic anemia.
When acquired autoimmune hemolytic anemia is secondary to other diseases, diagnosis and treatment of the underlying disorder usually brings marked improvement of the anemia. Mild cases may require no treatment. Individuals with more severe cases of warm antibody hemolytic anemia may be treated with oral steroids or intravenous hydrocortisone followed by divided daily oral doses of prednisone. Improvement usually occurs within five to ten days after treatment.
If the response to the steroid therapy is unsatisfactory, other therapeutic approaches must be considered.
In some resistant cases, total removal of the spleen may be required. Immunosuppressive drugs such as oral azathioprine or cyclophosphamide may be administered. Blood transfusions may be required in the most severe cases.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
Petz LD. Autoimmune Hemolytic Anemias. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:367.
Berkow R, ed. The Merck Manual-Home Edition.2nd ed. Whitehouse Station, NJ: Merck Research Laboratories; 2003:991-92.
Beers MH, Berkow R, eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:872-74.
Hoffman R, Benz Jr EJ, Shattil SJ, et al., eds. Hematology: Basic Principles and Practice. 2nd ed. Churchill-Livingstone, Inc. New York, NY; 1995:715-29.
Svensson AM, Bushor S, Fung MK. Case report: exacerbation of hemolytic anemia requiring multiple incompatible RBC transfusions. Immunohematol. 2004;20:177-83.
Elhajj II, Sharara AI, Taher AT. Chronic hepatitis C associated with Coombs-positive hemolytic anemia. Hematol J. 2004;5:364-66.
Kakaiya R, Cseri J, Smith S, et al. A case of acute hemolysis after ceftriaxone: immune complex mechanism demonstrated by flow cytometry. Arch Path Lab Med. 2004;128:905-07.
Lee Jm, Chan K, Kan YW, et al. Targeted disruption of Nrf2 causes regenerated immune-mediated hemolytic anemia. Proc Natl. Acad Sci U S A. 2004;101:9751-56.
Berentsen S, Ulvestad E, Gjertsen BT, et al. Rituximab for primary chronic cold agglutinin disease: a prospective study of 37 courses of therapy in 27 patients. Blood. 2004;103:2925-28.
Webster D, Ritchie B, Mant MJ. Prompt response to rituximab of severe hemolytic anemia with both cold and warm autoantibodies. Am J Hematal. 2004;75:258-59.
Petz LD. A physician’s guide to transfusion in autoimmune haemolytic anaemia. Br J Haematol. 2004;124:712-16.
La Spina M, Russo G. New Drugs for childhood anemia. Minerva Pediatr. 2003;55:483-98.
Buetens EW, Ness PM. Red blood cell transfusion in autoimmune hemolytic anemia. Curr Opin Hematol. 2003;10:429-33.
Medical Encyclopedia: idiopathic autoimmune hemolytic anemia. MedlinePlus. Update date: 6/5/2003. 2pp.
Medical Encyclopedia: Immune hemolytic anemia. MedlinePlus. Update date: 5/2/2003. 2pp.
Medical Encyclopedia: Hemolytic anemia. MedlinePlus. Update date: 5/2/2003. 3pp.
Anemia. Mayo Clinic. June 02, 2003. 7pp.
The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional.
The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright.
National Organization for Rare Disorders (NORD)
55 Kenosia Ave., Danbury CT 06810 • (203)744-0100