Immune-mediated hemolytic anemia (IMHA)
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 IMHA, 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.
The condition may occur in any breed, but it is seen most commonly in the breeds listed below.
IMHA can occur at any age, but is most common in middle-aged female 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 IMHA(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.
Your veterinarian will suspect that your dog is anemic through physical examination. S/he will do some blood tests to find the cause. The diagnosis of IMHA is made by identifying antibodies on the surface of the red blood cells, and ruling out other causes of anemia.
For the veterinarian: In IMHA, the immune system destroys rbcs by coating them with immunoglobulin or complement. In most cases of IMHA, the rbcs are coated with incomplete (ie don't agglutinate rbcs in saline) and warm-type ( ie. react optimally at 35 - 40°C) autoantibodies, mostly IgG. Hemolysis may be intra- or extravascular (mostly in the spleen). Cold antibodies react optimally below 30°C, 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. Hallmarks of regenerative anemia include spherocytosis, autoagglutination, polychromasia, anisocytosis, and reticulocytosis. The absence of reticulocytosis does not preclude a diagnosis of IMHA; this 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: There may be minimal to moderate changes in liver enzyme levels depending on the acuteness and severity of the hemolytic crisis. With intravascular hemolysis, you may see hemoglobinemia and hemoglobinuria.
Saline autoagglutination is diagnostic of IMHA. 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 rouleaux 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 positive 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.
Dogs with IMHA are in a hypercoaguable state with increased risk of developing DIC or pulmonary thromboembolism.
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) Immunosuppressive therapy with corticosteroids is 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 may be given.
2) Blood transfusions 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 IMHA may experience future relapses.
For the Veterinarian: With severe IMHA (intravascular hemolysis or autoagglutinating or unresponsive to glucocorticoids alone), more aggressive therapy (cytotoxic agents combined with corticosteroids) may include azathioprine or cyclosporine. Danazol (an attenuated androgen) stabilizes red cell membranes and is used as an adjunctive therapy with corticosteroids.
Packed rbcs should be given based on the hematocrit and the condition of the dog to maintain adequate oxygen-carrying capacity. Prophylactic heparin may be given to reduce the risk of thromboembolism.
Dogs who have been diagnosed with IMHA should not be used for breeding, and it is preferable to avoid breeding their close relatives as well.
Miller E. Immune-mediated hemolytic anemia. In: Bonagura JD, Twedt DC, eds. Kirk's Current Veterinary Therapy XIV. Missouri: Saunders Elsevier, 2009:266-271.
O'Toole T. Immune-mediated hemolytic anemia. In: Côté E, ed. Clinical Veterinary Advisor Dogs and Cats. Missouri: Mosby Elsevier, 2007:66-68.
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