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

By: Dr. Leah Cohn

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Immune mediated hemolytic anemia is exactly what the name implies. "Anemia" is a deficiency of red blood cells, and may result from many causes including bleeding, failure to produce enough new red blood cells, or destruction of existing red blood cells. "Hemolysis" refers to the lysis, or destruction, of the red blood cells ("heme" is an essential component of red blood cells that allows them to carry oxygen). The term "immune mediated" simply states that in these cases the process of red blood cell destruction is carried out by the immune system.

The immune system is a complicated network of cells and products that are secreted from cells. In a healthy animal, these cells and their products recognize germs as being foreign, and they attack and destroy those germs. The immune system is designed to recognize the animal's own cells as being harmless, and to refrain from attacking the animal's own healthy cells. When an animal develops immune mediated disease, the immune system destroys the animals own cells rather than just germs. Sometimes the attack on the animal's own cells is accidental, and sometimes it is purposeful. A purposeful attack is said to be an "autoimmune" process. In those cases, the immune system thinks the animal's own cells are foreign, and attempts to destroy them. This destructive process may be directed against many different cell types, but when the cell type under attack is the red blood cell, immune mediated hemolytic anemia is the result.

The development of immune mediated disease is complicated and poorly understood. In some cases a trigger can be identified that may have precipitated the misdirection of the immune system, but in most cases, such a trigger is never found. IMHA, like most such diseases, occurs more often in females than in males. Young adult to middle aged animals are most likely to be affected, and dogs develop the disease much more frequently than do cats. While any dog may develop IMHA, cocker spaniel, Springer spaniel, miniature poodle, Finnish spitz, Irish setter, bichon frise and Old English sheepdog are more likely than most to be affected.

Immune mediated hemolytic anemia is a rapidly life-threatening disease. With severe anemia of any cause, the tissues are unable to receive adequate oxygen. In cases of IMHA, destruction of red cells results in a sudden, and often very severe, decrease in red blood cell numbers. Although there is usually a substantial increase in the number of new red blood cells produced within the bone marrow, production of new cells cannot keep up with the rapid destruction of cells. Unless the immune system's attack on the red cells can be curbed, the animal will die. Swift treatment may stop the attack, allowing the newly made red blood cells to replace those that were destroyed. Unfortunately, it is not always a simple matter to stop the immune attack, and there are many potential complications of IMHA. Although many animals treated for IMHA go on to live full lives, even those who receive appropriate therapy may succumb to the disease.

There are different forms or subtypes of IMHA. They are most commonly referred to as primary, secondary, intravascular and extravacular.

  • Primary – primary IMHA, also known as idiopathic IMHA, results from the antibody attacking the red blood cell membrane. There is no known underlying cause or trigger for this type of IMHA. Most cases of IMHA in dogs (over 75%) are categorized as primary.

  • Secondary – secondary IMHA results from the antibody attacking a membrane antigen that is exposed because of an underlying disease. There is an underlying cause for this type of IMHA. Underlying causes that can expose the membrane may include neoplasia (cancer), infections, reactions to drugs, toxins, allergic reactions to bee stings and blood transfusions. The most common cause for secondary IMHA is cancer. Possible drug triggers may include antibiotics (such as sulfonamides, cephalosporins, penicillins), vaccines and procainamide.

  • Intravascular – intravascular IMHA means that they red blood cells are being destroyed in the blood vessels.

  • Extravacular – extravascular IMHA means that they red blood cells are being destroyed outside of the blood vessels, most commonly destroyed by macrophages in the spleen and/or liver.

    Differential Diagnoses (Other Causes of Anemia)

    It is crucial that the diagnosis of IMHA be confirmed, because there are many causes of anemia other than IMHA. Both treatment and prognosis for these other causes are often quite different that that of IMHA. Other potential cause of anemia include:

  • Blood loss. Bleeding results in anemia, and the site of bleeding may not always be obvious. For example, an animal can lose a tremendous amount of blood through the gastrointestinal tract with the only evidence of bleeding being dark, tarry colored stools.

  • Decreased production of red blood cells. The bone marrow is responsible for producing a continuous supply of new red blood cells. Sometimes this production of new cells falls behind, either due to disease inside the bone marrow or from other diseases with affect the signals or materials needed for production of new red cells. Examples of disease within the marrow might include cancer, toxic damage to the marrow, and infection in the marrow. Examples of other diseases that might affect the production of new red blood cells include kidney failure, iron deficiency, or chronic infections anywhere in the body.

  • Hemolytic anemia is not always due to an immune system attack. Other causes of hemolytic anemia are possible.

  • Infection of the red blood cells can lead to hemolytic anemia. Examples of such infections would include Babesiosis or Hemobartonellosis.

  • Certain toxins can lead to hemolytic anemia. The metal zinc and certain foods (like onion and garlic) are examples of such toxins.

  • The mechanical destruction of red blood cells results in hemolytic anemia. Examples would include a twisted spleen, a severe form of heartworm disease in which a clump of worms occludes the major blood vessels, or widespread formation of tiny blood clots (disseminated intravascular coagulation).

  • Certain hereditary diseases result in the formation of abnormal red blood cells. These abnormal cells are more likely to be destroyed, potentially resulting in hemolytic anemia.

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