What is Immune Mediated Hemolytic Anemia (IMHA in dogs)?

Please understand the following information is offered as a courtesy and is not intended to provide a diagnosis or medical recommendation for your pet.

In IMHA in dogs, markers called antibodies, stick to the red blood cells and cause the body to believe the red blood cells are a “foreign invader”. This causes the immune system to “kick in”, attack the red blood cells and destroy them. The mechanism by which the immune system mistakes the red blood cells for a “foreign invader” varies somewhat according to the cause. It usually involves adherence of the offending agent (parasite, drug or toxin) to the surface of the red blood cells. The immune system wishes to attack the offending agent, but manages to injure the red blood cells as well. When the spleen and the rest of the immune system is working to rid the body of the old, diseased or damaged red blood cells, it is doing its job properly. When a large percentage of the cells are affected, and they are removed faster then they are replaced, IMHA results. The destruction of red blood cells often leaves recognizable cellular debris in the blood stream. In particular, a form of damaged red blood cell known as a spherocyte occurs. Finding spherocytes on a blood smear almost guarantees that some form of hemolytic anemia is occurring. Since this disorder does not stop the production of red blood cells, there are usually immature red blood cells in the bloodstream which can be detected on the blood smears as well.

What are the Symptoms of Immune Mediated Hemolytic Anemia in dogs?

The symptoms or clinical signs of IMHA can appear suddenly or they may be gradual and progressive. The signs are usually related to the lack of oxygen and manifest themselves in the form of weakness, lethargy, and an increase in the heart and respiration rate. Pale mucous membranes (gums, ears, eyelids) may be observed. The dog also may appear to be jaundice. This is due to a build up of bilirubin, one of the breakdown products of red blood cells. Vomiting or abdominal pain may be present. Owners may note the presence of blood in the urine or stool Also an increase in temperature may be observed in some dogs. A diagnosis of IMHA is made on the basis of these clinical signs as well as a CBC. A Coomb’s test should be performed to confirm the diagnosis. A small percentage of dogs that have IMHA will test negative on the Coomb’s test.

What is the Cause of Immune Mediated Hemolytic Anemia?

There many potential causes of IMHA including exposure to certain drugs, recent vaccinations, infections, nad cancer. Most of the time however a specific cause for IMHA is unrecognized.. There is strong evidence for a genetic factor in the development of AIHA. Although all breeds can be affected the Cocker spaniel, West Highland White terrier, English springer spaniel, Alaskan malamute, and Poodle are the most common breeds in our practice to get the disease. Females are affected with AIHA 3-4 times more frequently then males.

How is IMHA treated?

The cornerstone of treatment for IMHA in dogs is the drug prednisone. Prednisone is a corticosteroid drug that suppresses the immune system. Very high doses of this immunosuppressive drug are given initially in an effort to stop the destruction of red blood cells and thus induce a remission. Improvement usually occurs within a few days, if the dog is going to respond. The minimum dosage of prednisone given at the onset of AIHA is 1 mg per pound per day divided into two dosages. Some clinicians will prescribe an even higher dosage for dogs with a very low PCV. The dosage of prednisone should be tapered off very slowly over many months. The aim is to get the dog to the lowest maintenance dosage possible or off the drug completely. Some adverse side effects associated with prednisone usage are; increased thirst and urination, increased appetite resulting in weight gain, increased panting, muscle weakness and increased susceptibly to infections due to the suppressed immune system. Dexamethasone, a corticosteroid drug, which is five to seven times more potent then prednisone is also used in the treatment of IMHA

Prednisone is usually used in combination with another immunosuppressive drug called Imuran (azathioprine). Imuran is a “second-line” or “slow acting drug.” Clinical response may require up to 6 weeks. The principal adverse effect associated with Imuran is bone marrow suppression. Acute pancreatitis and hepatotoxicity have also been associated with Imuran. Because Imuran depresses the immune system, animals may be susceptible to infections or neoplastic illnesses (long term use).

Another potent drug used in the treatment of IMHA is Cyclosporine.

Cyclosporine has revolutionized organ transplantation in humans since its introduction in 1983. It has also been used in autoimmune diseases in humans and now is starting to be used in veterinary medicine for the treatment of autoimmune diseases, such as autoimmune hemolytic anemia. It is very important to measure blood cyclosporine levels when the drug is being used.The therapeutic range for cyclosporine is from 300-500 ng/ml (nanogram/milliliter). One reason that frequent blood testing is necessary with cyclosporine is that there can be a great deal of variability in its absorption. One dog may absorb a larger percentage of the prescribed dosage then another. Cyclosporine concentration blood tests called trough tests are not able to be done “in-house” at veterinary clinics nor do most outside labs run cyclosporine levels.

The blood for the trough test must be drawn at the exact time a dosage of cyclosporine is scheduled to be given. This allows the lowest amount of cyclosporine in the body to be measured on the trough test. Since cyclosporine saturates the tissue, the dosage may need to be adjusted from time to time, another reason trough testing is so important. Because cyclosporine interacts with a variety of other drugs it should be used with caution with other medications. To get the full benefit from cyclosporine the dog must be on a very strict feeding and dosing schedule. The diet must be consistent without any deviations in amount, type of food or feeding time. Because cyclosporine has a half life of only 19 hours it must be given every 12 hours. Cyclosporine is sold under the brand name Neoral.

Arava (leflunomide) is in a class of agents similar to that of cyclosproine and has been used in a few cases with anecdotal success. Clinical trails on the use of Arava in dogs with autoimmune hemolytic anemia were done at University of California, Davis in the late 1990’s.

Danazol is a drug primarily used as an adjunctive therapy with corticosteroids (such as prednisone) in the treatment of canine autoimmune hemolytic anemia. There is apparently synergism when Danazol is combined with corticosteroids for this purpose. Once remission is attained, some dogs may have their Danazol dosage reduced or other medications may be eliminated and the disease may be controlled with Danazol alone.

Blood transfusions can be used in dogs with autoimmune hemolytic anemia if necessary. However, adding foreign protein can actually intensify the crisis state, increase the amount of bilirubin and other breakdown products the liver must process and suppress the bone marrow’s natural response to anemia. If blood transfusions are given, they should be done only in a life threatening situation and then done with great caution. The blood must be typed and crossed matched to avoid further sensitization and exacerbation of the problem.

In January, 1998 the FDA approved the first artificial blood for use in canines called Oxyglobin. The primary advantage of Oxyglobin over whole blood is that it can deliver oxygen to the cells several times faster then real blood and thus provide an “oxygen bridge” to the cells. This may give the body the additional time it needs for the drugs to begin to work. Oxyglobin has a shelf life of up to two years and does not need to be typed and cross matched.

Splenectomy, the surgical removal of the spleen, is occasionally recommended for cases of autoimmune hemolytic anemia that have been nonresponsive to other forms of treatment. This surgery benefits the dog in two ways; less antibodies are made against the red blood cells and the primary organ responsible or the destruction of the red blood cells is removed.

What is the morality rate for autoimmune hemolytic anemia?

This disease despite with the emergence of cyclosporine still remains difficult to treat with mortality rates ranging from 40% to 60%. The good news is if they respond they usually return to a normal life.

How long should I expect my dog’s recovery to take?

Each dog diagnosed with IMHA will have a different recovery time. Some dogs will respond to the drugs very quickly and have a rapid recovery. Other dogs will respond much more slowly and a variety of drugs may need to be tried before the right one/ones are found that will put the dog in remission. The most important point is that it takes at least five days to usually see a response from the medications.