Immune Mediated Hemolytic Anemia

by Nancy McDonald RN, BSN

Immune-mediated hemolytic anemia is a condition where the patient’s immune system begins to attack its own red blood cells. Microscopically, the branch of the immune system that produces antibodies begins to direct them against the patient’s own red blood cells. Red blood cells become quickly coated with tiny antibody proteins, essentially marking these red blood cells for destruction. When cells circulate through the spleen, liver, and bone marrow, they are plucked from circulation and destroyed, a process called “extravascular hemolysis.” Iron is sent to the liver as bilirubin for recycling. The spleen enlarges as it is processing far more damaged red blood cells than it normally does. The liver is overwhelmed by large amounts of iron-pigmented billirubin, and the patient becomes jaundiced. To make matters worse, a special protein system called the “complement system” is activated by these antibodies. Complement proteins are able to simply rupture red blood cells if they are adequately coated with antibodies, a process called “intravascular hemolysis.” Ultimately, enough red blood cells are not left circulating to bring adequate oxygen to tissues and remove waste gases. A life-threatening crisis has emerged. Mortality rates of 20% to 80% have been reported with the disease.

How sick the patient is may depend upon how quickly he is “hit with it.” The dog is weak, has no energy and has lost interest in food, may have vomiting and diarrhea; its heart rate and breathing are rapid. Urine is dark orange to brown. Gums are pale or yellow-tinged as are the whites of the eyes. Fever could be present; liver and spleen are enlarged. Obviously, something is terribly wrong.
First, the veterinarian will determine that the pet is anemic by a test usually run in the office called a packed cell volume or submit blood to a reference laboratory for a full blood panel. Diagnosis of IMHA may rely on exclusion of other causes of other hemolytic anemia, concurrent with certain laboratory findings.
Anemias can be “non-responsive” and “responsive.” “Non-responsive” anemia is due to poor red blood cell production by the bone marrow caused by chronic inflammatory diseases (like inflamed skin, infected teeth, or other long standing irritations), kidney failure, cancers of various types, or certain drugs, (especially agents of chemotherapy). Conversely, in “responsive anemia”, bone marrow production increases due to loss of red blood cells and lack of blood oxygen. Both bleeding and immune-mediated red blood cell destruction are “responsive anemias.” By looking at results of the “complete blood count” or “CBC” on the blood panel from the reference lab, it can be determined if the anemia is responsive or not. With responsive anemia, it has to be determined if red blood cell loss is due to bleeding, possibly internal, or are they being destroyed by the immune system.
Once again, several clues from the blood panel tell if a patient is bleeding or destroying red blood cells. One of these clues is “icterus” or “jaundice”. Bilirubin is iron left after a red blood cell has been destroyed. Normally red blood cells are removed from circulation when they become old. Iron is recycled in the liver. When the liver is overwhelmed with large amounts of bilirubin (a yellow pigment), it spills out everywhere, coloring urine, gums, skin and eyes orange. Icterus can also result from liver failure when the diseased liver cannot process normal amounts of bilirubin. However, a responsive anemia together with icterus, suggests immune-mediated red cell destruction.
Presence of special red blood cells called spherocytes is another clue found in the blood panel. Spherocytes are produced when the spleen does not completely remove a red blood cell. The spleen takes a bite out of the red blood cell and it reshapes and changes color thus indicating that red blood cell destruction is taking place.
Autoagglutination occurs in severe cases of immune-mediated hemolytic anemia when the immune destruction of red cells is so blatant that red cells clump together (because their antibody coatings stick together) when a drop of blood is placed on a microscope slide. This finding is especially foreboding.
Also, the blood panel of immune-mediated hemolytic anemia will show a “leukemoid reaction,” a high white cell count. In immune-mediated hemolytic anemia, the stimulation of the bone marrow to produce red blood cells is so strong that even the white blood cell lines are stimulated.
A state of the art blood test to identify antibodies coating red blood cell surfaces is called “Coomb’s”test, also called a “direct antibody test.” However, the human version of this test is not very accurate in dogs. Kansas State University College of Veterinary Medicine developed a test that will accurately identify those dogs with the disease. Other universities also have this test.
With a diagnosis of immune-mediated hemolytic anemia, efforts should be made to determine an underlying cause. With primary disease, the process is spontaneous with no identifiable trigger (the immune system targets normal blood cells). Other possible causes or triggers are drugs (penicillin or sulfonamides), tick born parasites (Erlichia and Babesia), viruses or bacteria. Recent observation has led to consideration that vaccination can trigger IMHA, which has led to most universities recommending a 3 year schedule for standard DHLPP vaccines, breaking them down to Core and Non-Core vaccines, based on specific criteria. Certain breeds, primarily spaniels, poodles and setters, are predisposed to develop the disease, though it can occur in any breed of dog. It can also manifest as part of other immune-mediated diseases as they attack multiple organs concurrently, especially systemic lupus erythematosus or rheumatoid arthritis.
Treatment of choice is to suppress the immune system using high doses of corticosteroid hormones. These hormones are directly toxic to lymphocytes, cells that produce antibodies. If the patient’s red blood cells are not coated with antibodies, they will not be targeted for removal so stopping antibody production is very important. Corticosteroid hormones also suppress the activity of cells that are responsible for removal of antibody-coated red cells. Corticosteroids may be the only immune suppressive medications the patient needs. It is likely the patient will be on a high dosage of corticosteroids for weeks or months before the dose is tapered down. If the drug is withdrawn too soon, hemolysis will begin all over again. Sometimes a patient must always be on a low dose to prevent recurrence. Unfortunately, severe and dangerous side effects are associated with long-term steroid use. However, in the case of immune-mediated hemolytic anemia, there is no way around it. It is important to remember that undesirable steroid effects will diminish as the dosage diminishes.
Some dogs do not respond to corticosteroid treatment and require more potent immunosuppressive drugs that are often combined with corticosteroid treatment. These cytotoxic agents are commonly used in chemotherapy to inhibit cell division and can produce severe side effects. Other treatments used are immune-modulator drugs used in organ transplantation and human gamma globulin transfusions. These are extremely expensive, adding greatly to the cost of treatment.
The patient with IMHA is often unstable. General supportive care is needed to maintain the patient’s fluid balance and nutritional needs. Most importantly, the hemolysis must be stopped by suppressing the immune system’s rampant red blood cell destruction. If red blood cell levels get dangerously low, blood transfusions are needed to buy time until treatment becomes effective. Well-matched whole blood or packed red cells are ideal. With IMHA, the patient’s own red blood cells are being destroyed as well as the transfused red blood cells. Consequently, it is not unusual for a severely affected patient to require many transfusions. Artificial blood and bovine blood are available although neither last long in the body.
IMHA is treated with immunosuppressive medications. Therefore you pet will be a increased risk of infections. The most common area of infections is the urinary tract but also skin and respiratory system is at risk. These systems should be monitored closely for any changes. Raw food diets pose a risk of causing infections and should not be given to pets with immune mediated thrombocyopenia.
A leading cause of death for dogs (between 30-80%) is due to thromboembolic disease when mini-clots travel through the body and occlude smaller vessels thus interfering with circulation. Heparin, a blood thinner, may be used in hospitalized patients as a preventive.
Presently, IMHA carries a guarded prognosis, particularly when multiple body systems are affected, but veterinary researchers are investigating new methods of treatment. If your dog has been diagnosed with IMHA, be prepared for a long and emotionally draining battle knowing that with your support and the hard work of your veterinarian, you can make its days more comfortable.
Merck Veterinary Manual
Updated and review, 2016