Cavalier Health Issues



Immune Mediated Hemolytic Anemia (IMHA)

by Dr. Leanne Bertani

Autoimmune Hemolytic Anema (AIHA), also known as Immune Mediated Hemolytic Anemia (IMHA), is a life-threatening condition due to antibodies that cause the destruction of red blood cells. Primary AIHA is when antibodies are formed against normal red blood cell membranes. Secondary AIHA is when antibodies are formed to abnormal red blood cell membranes, as may occur with infection, cancer, reaction to drugs, or even bee stings.

Breeds that seem to be prone to AIHA are Old English sheepdogs, cocker spaniels, poodles, Irish setters, English springer spaniels, West Highland white terrier, malamute, beagle, and collies. However, there are also instances of AIHA in other breeds; including many cases resulting in the death of toy breed dogs. Females are more often affected than males, and middle-aged dogs more often affected than puppies or elderly dogs.

Symptoms

The main symptoms of AIHA are caused when the body destroys red blood cells faster than it makes them, leaving the body with too few cells to carry sufficient oxygen to the tissues. This lack of oxygen will manifest itself as exercise intolerance, including weakness, shortness of breath, or even collapse. A heart murmur, or even heart failure, may develop as the heart beats too quickly in its bid to keep up with the need for oxygen.

The mucous membranes (such as the gums) may be pale, due to decreased red blood cells. If there is an associated destruction of platelets (thrombocytopenia), hemorrhages, bruising, and bleeding may occur.

The increase in destruction of red blood cells causes bilirubin to be elevated in the bloodstream. This can cause jaundice (sometimes noticed as a yellow tinge to the whites of the eyes), nausea and vomiting. Lack of oxygen to the cells in the kidney and liver can cause renal failure and liver necrosis.

Laboratory Tests

A CBC (Complete Blood Count) will be done, as well as a PCV (Packed Cell Volume). The PCV is a measure of the number of red blood cells, and may be done frequently to gauge how well the dog is responding to treatment. The reticulocyte count is a test for "newly made" red blood cells. It will tell if the body is working to produce new red blood cells to try and keep up with the destruction.

Tests to rule out secondary causes of AIHA may also be done, such as blood tests for Leptospirosis, Hemobartonella, Babesia, Ehrlichia, and heartworm. X-rays and ultrasounds may be used to gauge damage to organ systems.

A Coomb's test may be done as a measure of immune reactions, and is positive in about 60% of cases of AIHA. Another test, not as readily available, is the Direct ImmunoFluorescent (DIF) assay. It detects IgG, IgM, IgA, and C3 on red blood cells of dogs with immune mediated hemolytic anemia. The DIF test is said to be more sensitive than the Coombs test.

Treatment

The dog will usually have to be hospitalized, at least until the PCV is stable. Blood or blood substitute transfusions and IV fluids may be necessary. The mainstay of treatment is to use immunosuppressants such as prednisone, to depress the immune system's attack on the red blood cells. Other drugs that might be used include prednisilone, dexamethasone, danazol, leflunomide, cyclosporine, azathioprine, cyclophosphamide, chlorambucil, eicosapentanoic acid and human gamma globulin. Plasmapheresis, a process where the antibodies are removed from the blood, may also be done. Surgical removal of the spleen (because it is a site of red blood cell destruction) may be recommeded if the dog doesn't respond to medical therapy. A complication of splenectomy is that it may leave the dog a bit more vulverable to infections in the future.

Prognosis

If the dog survives the initial hospitalization, medication may be required for weeks, months or even life.

The overall fatality rate for AIHA is probably somewhere between 30 and 70%. Of the dogs that seem to recover in the hospital, some will relapse within the weeks following their release. The prognosis is worse if the bilirubin is very high or the reticulocyte count is very low. Prognosis is poor if the disease is complicated by Disseminating Intravascular Coagulation (DIC), a coagulation disorder that sometimes follows serious illnesses.

Prevention

While some cases of immune-mediated anemia are just plain unavoidable, there are a few measures which theoretically may decrease the prevalence of the condition in our dogs.

Because autoimmune disease may be triggered by drugs (especially sulfa drugs) and viruses, medications should only be given when benefits clearly outweigh the risks, and exposure to sick animals should be avoided, as should exposure to venomous animals and insects. Likewise, it is probably reasonable to avoid exposure to lawn chemicals, and to keep exposure to insecticides to a minimum.

There is some evidence that there may be a genetic predisposition to the body's tendency to attack itself. It may be wise to avoid breeding from families of dogs with a high incidence of autoimmune diseases such as AIHA, Addison's Disease, Thyroiditis, Lupus, Myositis, Myasthenia Gravis, Rheumatoid Arthritis, etc.

Recent studies suggest that the common practice of annual vaccination for viral diseases may be overstimulating our dogs' immune systems. The practice of automatic annual vaccines for every known disease should quickly become a thing of the past. Instead, vaccination protocols should be individualized to each dog's specific needs.

References:

1. J Am Vet Med Assoc 1999 Apr 1; 214(7):1026-7, 1021 Bee sting envenomation resulting in secondary immune-mediated hemolytic anemia in two dogs. Noble SJ, Armstrong PJ 2. J Am Anim Hosp Assoc 2001 Jan-Feb;37(1):11. Immune-mediated hemolytic

anemai: 70 cases 1988-1996. Reimer ME, Troy GC, Warnick LD. 3. Duval D, Giger U. Vaccine-induced immune-mediated hemolytic anemia in the dog. J Vet Intern Med 1996. Sep-Oct;10(5):290-5. 4. Hogenesch H, et al. Vaccine-induced autoimmunity in the dog. In: Schultz RD, ed. Advances in Veterinary Medicine 41: Veterinary Vaccines and Diagnostics. San Diego: Academic Press, 1999; 715-732 5. Tilley Larry P, Smith Francis WK, The 5-Minute Veterinary Consult. Williams & Wilkins 1997. pp 344-345.