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Immune Mediated Hemolytic Anemia in Dogs (IMHA), Autoimmune Hemolytic Anemia

By: Dr. Leah Cohn

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Treatment of IMHA involves both direct attempts to halt the immune system attack on the red blood cells, and supportive care. The immune system is a complicated network of cells and cell products all designed to protect the body from foreign invaders. As with any complicated system, there are multiple places where errors can occur. When these errors result in the destruction of red blood cells (that is, IMHA), the immune system's attack must be halted if the animal is to survive. Unfortunately, the drugs available to halt the attack are not specific, meaning that they not only diminish the attack on the red blood cells, but also interfere with appropriate immune response to germs. This puts the animal undergoing therapy for IMHA in the precarious position of needing just enough, but not too much, immune suppression.

The drugs available to suppress the immune system interfere with entire pathways of immunity, and occasionally more than one of these paths must be interrupted to stop destruction of the red blood cells. In most dogs that respond successfully to therapy, the dose of immunosuppressive drugs can be very gradually lowered. Some animals will eventually be able to discontinue medications altogether, while others will require life-long therapy. Almost all immunosuppressive therapies require some time to take effect. Until the destruction of red cells can be halted, supportive care is crucial for the animal's survival.

  • Corticosteroids (such as prednisone, prednisolone, or Dexamethasone) suppress the immune system's attack on the red cells by several mechanisms and are the mainstays of treatment for IMHA. While the effect of corticosteroids is more rapid than that of many other immunosuppressive drugs, it is still often 3 to 4 days before a positive response may be seen. Initial dosages of corticosteroids are very high, and may be associated with unpleasant side effects such as increased thirst and appetite, along with increased urination and weight gain. The dosage will be slowly decreased over several months after the animal improves.

  • In the most severe cases, or those cases that fail to respond to corticosteroids, other immunosuppressive agents may be utilized. These include drugs such as azathioprine, cyclophosphamide, cyclosporine, danazol, or leuflonomide. Unfortunately, there are no good studies proving that any of these other medications are particularly helpful in the treatment of IMHA. Each will be discussed briefly.

  • Azathioprine (Imuran®) is a drug that is toxic to the type of immune cell (lymphocytes) that produces antibodies. By destroying some of these cells, less antibody is produced to both red blood cells and to germs. It takes at least a week for azothiprine to become effective.

  • Cyclophosphamide (Cytoxan®, Neosar®)is another drug that is toxic to lymphocytes, and it is also used to treat lymphatic cancer. In the small number of studies where it has been evaluated, the response of IMHA to cyclophosphamide has been very disappointing.

  • Cyclosporine (Atopica®, Optimmune®) is the same drug used to prevent rejection of transplanted organs. It suppresses immunity by affecting molecules known as cytokines that are secreted from immune cells. There are few studies evaluating how effective this expensive drug is in the treatment of IMHA.

  • Danazol is a synthetic molecule related to testosterone that has been used to suppress the immune attack in IMHA, although the way in which it does so is not clear. This medication is very expensive, and has not been proven effective.

  • Leflunomide is one of the newer medications used to treat refractory cases of IMHA. Again, there are no studies yet proving that this expensive medication is effective.

  • Intravenous immunoglobulins, a product made from human blood, has been used with some success in a few cases of IMHA. The human antibodies (immunoglobulins) are thought to compete with the animal's own antibody-coated red cells for the attention of other immune cells. This therapy is very expensive, and supplies of this human product to veterinarians are often limited by supply.

  • Gastrointestinal protectant drugs, such as Famotidine (Pepcid®), Cimetidine HCl (Tagamet®), or Ranitidine HCl (Zantac®) may be used.

  • Plasmapheresis, or the process of removing antibodies from the blood, is very rarely available to veterinarians, but may be possible in some special hospitals. The animal's blood is removed from the body, the excess antibodies are "washed" away, while the rest of the blood is returned to the animal.

  • Because the spleen is responsible for removing many of the antibody-targeted red cells, splenectomy (removal of the spleen) may benefit some animals after initial treatment and stabilization. This is not an emergency therapy, but is useful in animals that continue to require high drug doses to maintain remission from disease.

  • Supportive care is essential to the successful treatment of IMHA. Such care may include transfusion, nursing, and medications.

  • Transfusion of either whole blood (cells plus the liquid plasma) or of packed red blood cells (cells only after the liquid is removed) may prove life saving by allowing the transfused red blood cells to carry oxygen to the tissues. Unfortunately, animals with IMHA destroy not only their own red cells, but the transfused cells as well. In fact, the transfused cells may be destroyed even faster than the animals own cells would, and this destruction may contribute to complications of IMHA. In general, transfusion will be postponed for as long as possible in the hope that the animal will improve in response to corticosteroids. However, many dogs will die of anemia and blood transfusion may be required to support them until they can respond to the drug therapy.

  • Administration of a blood substitute (Oxyglobin®) provides the ability to carry oxygen to the tissues without administering blood itself. The advantage is that there are no cells to be destroyed, but the blood substitute itself only lasts for a few days.

  • Heparin is an injectable medication that helps prevent formation of blood clots. Complications of IMHA include two types of abnormal blood clotting. The first is formation of blood clots that lodge in the blood vessels of the lungs (pulmonary thromboembolism). The second involves widespread clotting (and subsequent lysis of clots) of blood inside the vessels (disseminated intravascular coagulation). Either complication may prove fatal.

  • Intravenous fluids may be indicated some pets. Intravenous catheters are required for fluid therapy, and may make formation of clots more likely. However, it is vital to maintain adequate hydration and flow of blood, so the benefits of intravenous fluid therapy may outweigh the risks in some cases.

    Prognosis

    The prognosis depends on the pet's response to treatment and the diagnosis and treatment of any possible underlying cause for the disease. The prognosis is generally considered poor. The mortality rate is estimated to be 40 to 60% in dogs. Some dogs may relapse within the first year.

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