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

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Because we do not understand what causes IMHA, there are no known preventive measures. If an animal’s gums are noted to be pale or white, and the animal appears weak, seek emergency veterinary assistance.

In-depth Information on Immune Mediated Hemolytic Anemia in Dogs (IMHA)

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) in Dogs

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.

In-depth Information on the Diagnosis of Canine Immune Mediated Hemolytic Anemia in Dogs (IMHA)

Expect your veterinarian to obtain a complete medical history. Be prepared for questions about what symptoms you have observed and how long they have been present, any medications your animal may have received, when the most recent vaccinations were given, and questions about the color of urine and stool.

  • A complete physical examination will be performed. Your veterinarian will evaluate the color of the gums and the eyes, palpate the abdomen looking for masses or swellings, and listen to the chest for heart murmurs or abnormal lung sounds.
  • A complete blood count (CBC) should be performed on all dogs suspected of having anemia (decreased number of red blood cells), regardless of the cause. This will not only quantify the number of red cells present, but will allow for a visual inspection of the cells under the microscope. Certain characteristic changes are often noted in the remaining red blood cells of animals with IMHA.
  • A “packed cell volume”, or PCV, is a quick and simple test for the number of red blood cells present. Your veterinarian may do this test on a daily or near daily basis both initially and as therapy progresses to evaluate the balance between production of new cells and destruction of the old.
  • Reticulocyte counts allow the veterinarian to determine if new red cells are being made in appropriate quantities. The rapid production of new red cells is not only important for the animal, but helps the veterinarian rule out other causes of anemia from diagnostic consideration.
  • A serum biochemical profile and urinalysis may be performed to give clues as to possible causes of the anemia.
  • A saline agglutination test is a simple blood test that may show if the red cells are clumping together. In some forms of IMHA, the red cells actually stick together. If true agglutination is proven, it cements a diagnosis of IMHA.
  • A Coombs test is often indicated. A sample of the dog’s blood is incubated with special reagents to look for evidence of an immune reaction to the blood. This test is very useful, but there are several causes of false positive results (for instance, prior transfusion) or of false negative results (for instance, prior corticosteroid therapy).
  • Coagulation tests such as the activated partial thromboplastin time, prothrombin time, fibrinogen, platelet count and/or fibrin degradation products) may be done to determine the ability of the blood to clot. Some dogs can develop a secondary condition called disseminated intravascular coagulation (DIC), which can cause a cascade of secondary problems. For more information on DIC, go to “Disseminated Intravascular Coagulation (DIC) in Dogs.”
  • Newer, specialized tests search for evidence of an immune reaction to the red blood cells in more sophisticated ways that the traditional Coombs test. Direct immunofluorescence flow cytometry is an example of such a test; while this test is less likely to give a false negative result for an animal that has IMHA, it is also more likely to give a false positive result for an animal that does not have IMHA.
  • Radiographs, ultrasound examinations, or blood tests for infectious diseases may be indicated in some patients. These examinations may help rule out causes of anemia other than IMHA, or may help identify triggers that preceded development of IMHA.
  • Occasionally, IMHA destroys not only the red blood cells in circulation, but also the immature red cells being produced in the bone marrow. In this case, a bone marrow aspirate may be indicated. A large needle is placed in the bone while the animal is sedated, and a small sample of marrow is removed for microscopic analysis.

In-depth Information on the Treatment of Canine Immune Mediated Hemolytic Anemia

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.

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