Information on the following diseases can be found in the Related Disorders section of this report:

• Paroxysmal Nocturnal Hemolytic Anemia
• Chronic Lymphatic Leukemia
• Lymphoma
• Lupus Erythematosus

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.

Symptoms of the following disorder can be similar to those of Acquired Autoimmune Hemolytic Anemia. Comparison may be useful for a differential diagnosis:

Paroxysmal Nocturnal Hemoglobinuria is a disorder characterized by a decrease of red blood cells (anemia) caused by a defect in the membrane of the red blood cells. The major symptom is the presence of blood in the urine (hemoglobinuria) which occurs chiefly at night due to the breakdown of red blood cells. Other symptoms may include paleness, severe abdominal or back pain, yellowing of the skin (jaundice) and enlargement of the spleen and liver. (For more information on this disorder, choose "Paroxysmal Nocturnal Hemoglobinuria" as your search term in the Rare Disease Database.)

The following disorders may precede the development of Acquired Autoimmune Hemolytic Anemia. They can be useful in identifying an underlying cause of some forms of this disorder:

Chronic Lymphatic Leukemia is a disorder characterized by an excessive amount of white blood cells in the bone marrow, spleen, liver and blood. As the disease progresses, the leukemic cells invade other areas of the body including the intestinal tract, kidneys, lungs, gonads and lymph nodes. Symptoms of Chronic Lymphatic Leukemia may include fatigue, weakness, itchiness, night sweats, abdominal discomfort or weight loss. An enlarged spleen is usually discovered upon physical examination. People with this type of leukemia can get Acquired Autoimmune Hemolytic Anemia. (For more information on this disorder, choose "Chronic Myelogenous Leukemia" as your search term in the Rare Disease Database.)

Lymphoma is a malignant growth which most commonly occurs in the lymph nodes, spleen and other areas involved in the body's immune system (lymphoreticular system). The major types are Hodgkin's Disease and Non- Hodgkin's Lymphoma. People with Lymphoma can get Acquired Autoimmune Hemolytic Anemia . (For more information on this disorder, choose "Hodgkin" or "Lymphoma" as your search term in the Rare Disease Database.)

Lupus Erythematosus is an inflammatory connective tissue disease that can affect many parts of the body including the joints, skin and internal organs. Lupus is an autoimmune disease most often striking young women between the ages of 15 and 35 years. The symptom for which Lupus was originally named, a butterfly-shaped red rash across the bridge of the nose and cheeks, is found in only five percent of newly diagnosed patients. Far more common are arthritic symptoms such as painfully inflamed joints. People with Lupus can get Acquired Autoimmune Hemolytic Anemia. (For more information on this disorder, choose "Lupus" as your search term in the Rare Disease Database.)

Diagnosis
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.

Treatment
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
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, in the main, contact:
www.centerwatch.com

TEXTBOOKS
Petz LD. Autoimmune Hemolytic Anemias. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:367.

Beers MH, Berkow R, eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:872-74.

Berkow R, ed. The Merck Manual-Home Edition.2nd ed. Whitehouse Station, NJ: Merck Research Laboratories; 2003:991-92.

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.

REVIEW ARTICLES
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.

JOURNAL ARTICLES
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.

FROM THE INTERNET
Medical Encyclopedia: idiopathic autoimmune hemolytic anemia. MedlinePlus. Update date: 6/5/2003. 2pp.
www.nlm.nih.gov/medlineplus/ency/article000579.htm

Medical Encyclopedia: Immune hemolytic anemia. MedlinePlus. Update date: 5/2/2003. 2pp.
www.nlm.nih.gov/medlineplus/ency/article000576.htm

Medical Encyclopedia: Hemolytic anemia. MedlinePlus. Update date: 5/2/2003. 3pp.
www.nlm.nih.gov/medlineplus/ency/article000571.htm

Anemia. Mayo Clinic. June 02, 2003. 7pp.
www.mayoclinic.com/invoke.cfm?id=DS00321