related term: immune-mediated hemolytic anemia

What is autoimmune hemolytic anemia (AIHA)?

Normally red blood cells live about 4 months in dogs. As the cells age, they are removed and destroyed by other cells that are part of the immune system. New red blood cells are produced in the bone marrow at a rate that matches the destruction of older cells.

In autoimmune hemolytic anemia, the immune system destroys red blood cells prematurely, faster than the rate at which new ones can be produced. The name says it all - anemia (reduced red blood cells) caused by hemolysis (destruction) by the body's own immune system (autoimmune).

How is autoimmune hemolytic anemia inherited?

Inheritance is unknown, but the condition is more common in certain breeds.

What breeds are affected by autoimmune hemolytic anemia?

The old English sheep dog, cocker spaniel, and poodle have an increased susceptibility to this disorder, although it occurs in all breeds. It is more common in females than males.

For many breeds and many disorders, the studies to determine the mode of inheritance or the frequency in the breed have not been carried out, or are inconclusive. We have listed breeds for which there is a consensus among those investigating in this field and among veterinary practitioners, that the condition is significant in this breed.

What does autoimmune hemolytic anemia mean to your dog & you?

AIHA can occur at any age, but is most common in middle-aged dogs. It may be mild and hardly noticeable, or it may be sudden in onset and severe. Usually the kinds of signs you see are vague - such as poor appetite, weakness, listlessness, lack of energy. You may notice that your dog's gums are pale, or they may be yellowish due to jaundice as a result of the breakdown of red blood cells. Your pet may have a rapid heart beat and rapid breathing. One form of AIHA (cold agglutinin disease) causes circulation problems in cooler peripheral parts of the body, so the ear or tail tips, or feet may become infected and dark in colour.

Reduced levels of circulating red blood cells mean reduced oxygen going to the tissues. Most dogs that die with this condition do so in the first few days due to kidney, liver, or heart failure, or because of a bleeding problem.

How is autoimmune hemolytic anemia diagnosed?

Your veterinarian will suspect that your dog is anemic through physical examination, S/he will do some blood tests to find the cause. Basically the diagnosis of AIHA is made by identifying antibodies on the surface of the red blood cells, and ruling out other causes of anemia.

For the veterinarian: In AIHA, the immune sytem destroys rbcs by coating them with immunoglobulin or complement. In most cases of AIHA, the rbcs are coated with incomplete (ie don't agglutinate rbcs in saline) and warm-type ( ie. react optimally at 35 - 40C) autoantibodies, mostly IgG. Hemolysis may be intra- or extravascular (mostly in the spleen).

Cold antibodies react optimally below 30C, and are virtually always IgM. These may cause rbc agglutination or hemolysis in the body periphery (ear tips, paws, tail).

CBC: The common picture is a highly regenerative anemia, sometimes with a dramatic reactive leukocytosis (neutrophilia and left shift) +/- thrombocytopenia. The appearance of schistocytes is highly suggestive of AIHA. The absence of reticulocytosis does not preclude the diagnosis; it may be due to recent onset (less than 3 days) or destruction of young rbcs in the bone marrow. Bone marrow aspiration should be done if there is a persistent reticulocytopenia, to rule out other primary bone marrow disorders.

Biochem. profile: You will commonly see elevated serum bilirubin, LDH and ALT.

With intravascular hemolysis, you may see hemoglobinemia and hemoglobinuria.

Saline autoagglutination is diagnostic of AIHA. Mix 1 drop of anticoagulated whole blood with 1 drop physiologic saline on a microscope slide. If enough antibody molecules are present on the rbcs, you will see agglutination (not to be confused with rouleau formation, which will quickly disperse unlike autoagglutination).

The DAT (direct antiglobulin test, or Coomb's test) is used to detect antibodies on rbcs, when levels are too low to cause autoagglutination. The test is positve in about 60% of cases. The DAT may be negative due to a low number of immunoglobulin molecules on the red cell, problems with the test, immunosuppressive treatment, or an incorrect diagnosis. 

Other potential complications include DIC (signs of bleeding will predominate), thrombocytopenia, and pulmonary thromboembolism (may see dyspnea despite normal cardiac function and an adequate Hct; hypoxemia and normocapnea on arterial blood gas; pronounced interstitial pattern on radiographs).

How is autoimmune hemolytic anemia treated?

Unfortunately, dogs severely affected with this condition may die even with the best treatment. This mostly occurs in the first few days due to kidney, liver, or heart failure, or because of a bleeding problem. The goals of treatment are (1) to slow the destruction of red blood cells (rbcs), and (2) to support the dog while the red blood cell level has a chance to recover.

1) Corticosteroids are given to slow rbc destruction, initially at high doses which are gradually tapered over several weeks as rbc levels stabilize and begin to rise again. If rbc levels continue to fall despite steroid therapy, other immunosuppressive drugs are given.

2) Blood transufusions are needed when the rbc level is critically low. Although the new cells will also be destroyed at the same rate, the transfusion will buy some time for the dog while his/her own blood cell levels are recovering.

Dogs that recover from an episode of AIHA may experience future relapses.

For the veterinarian: More aggressive therapy (cytotoxic agents combined with corticosteroids) shoud be attempted in autoagglutinating or nonregenerative forms of IMHA, or dogs with fulminant IV hemolysis. Azathioprine or cyclophosphamide may be used.

Danazol (an attenuated androgen) stabilizes red cell membranes and has been used successfully in human medicine as a valuable adjunct or alternative to corticosteroids. It may be beneficial in veterinary medicine as well.

Packed rbcs should be given based on the hematocrit and on the condition of the dog, to prevent problems caused by hypoxia such as ventricular arrhythmias, hepatic centrilobular necrosis, and renal tubular necrosis. Generally dogs with a Hct of 12-15% should be transfused, and those in critical condition or those with co-existing heart or lung disease at 15-20%. Autoagglutination may make typing and cross-matching impossible, in which case DEA-1 negative donors should be used.

Prophylactic heparin may be given in fulminating AIHA to decrease the risks of DIC, but its use is controversial where there is bleeding due to DIC and severe thrombocytopenia.

Breeding advice

Dogs who have been diagnosed with AIHA should not be used for breeding, and it is preferable to avoid breeding their close relatives as well.

FOR MORE INFORMATION ABOUT THIS DISORDER, PLEASE SEE YOUR VETERINARIAN.

Resources

Bucheler, J., Coter, S.M. 1995. Canine immune-mediated hemolytic anemia. In J.D. Bonogura and R.W. Kirk (eds.) Kirk's Current Veterinary Therapy XII Small Animal Practice. p.152-157. W.B. Saunders Co., Toronto.

Cotter, S.M. 1996. Emergency management of autoimmune hemolytic anemia. ACVIM - Proceedings of the 14th Annual Veterinary Medical Forum, p. 40-41.

Thompson, J.P. 1995. Immunologic disease. In E.J. Ettinger and E.C. Feldman (eds.) Textbook of Veterinary Internal Medicine, p. 2002-2029. W.B. Saunders Co., Toronto.

Copyright 1998 Canine Inherited Disorders Database. All rights reserved.
Revised: July 23, 2001.

This database is a joint initiative of the Sir James Dunn Animal Welfare Centre at the Atlantic Veterinary College, University of Prince Edward Island, and the Canadian Veterinary Medical Association.