Immune-Mediated Hemolytic Anemia (IMHA)

Julie Stegeman, DVM

Immune-mediated hemolytic anemia (IMHA) is an autoimmune condition wherein the patient’s immune system attacks their own red blood cells as if they were a foreign invader. IMHA is more common in dogs than in cats, and it is an almost daily occurrence in the caseload of a referral hospital because of the need for inpatient supportive care and often the need for blood transfusion. It is most often seen in middle-aged dogs and in young cats, and some breeds are more at risk (cocker spaniels, miniature schnauzers, miniature dachshunds, etc). IMHA represents a loss of immune system “tolerance of self.” Our immune system has checks and balances built in, but when there is a disturbance in that balance, a red blood cell can “look” like a virus to an immune system cell. It then becomes a target for destruction, leading to severe anemia and death if left untreated.

Symptoms of IMHA initially can be vague. Lethargy, poor appetite, even a fever may be seen. Pet owners might notice a red or orange discoloration to the pet’s urine, or they might notice pale gums. The gums and skin might even appear yellow (“jaundiced”) due to buildup of bilirubin, which is a byproduct of red blood cell destruction. Orange stool is also commonly seen. These symptoms lead to taking the pet in to their veterinarian. Blood tests will show anemia and may or may not show elevated bilirubin levels, elevated white blood cells, low platelets, or elevated liver or kidney values. If the platelet count is low, the pet may have autoimmune destruction of their platelets as well—this is called Evan’s syndrome.”

It is recommended to screen for a variety of immune system triggers in an IMHA patient, such as various tick-borne illnesses, viral infections, other infectious diseases, and cancer. Other triggers can include a variety of medications and even (rarely) vaccinations. If there is an underlying triggering condition, the immune destruction will continue until the trigger is eliminated. This is especially important because treatment for IMHA requires immune suppressive medications, and if there is an infectious disease present, the immune suppressant medications will allow the triggering infectious disease to overcome the patient. It is very important to provide a full medical and travel history to the attending veterinarian, so that these issues can be discovered right away. Various blood tests, chest radiographs, and abdominal ultrasounds are usually performed to screen for underlying conditions, depending on the patient and their exact history.

If no inciting cause is identified, then immune suppressive treatment is begun. The cornerstone of immune suppressive treatment is glucocorticoid (steroid) treatment, most commonly in the form of prednisone or as injectable dexamethasone. High doses of steroids are required at first, because the immune reactions in IMHA are very intense, and progression is rapid if left unchecked. It can take several days to start to see the benefits of the immune suppressive treatments. In some patients, if the immune system is attacking red blood cells at the level of the bone marrow (where they are being produced), it can take 4 to 6 weeks for stabilization of the red cell levels to occur. Until the red cell level (often determined with a Packed Cell Volume [PCV]) stabilizes and starts to increase, blood transfusions are often necessary. Transfusions help “buy time” until the steroids can control the situation. Unfortunately, the transfused red blood cells are often destroyed as quickly as the pet’s own red blood cells, so repeated transfusion may be needed.

Dr. Stegeman with Kiss»

In addition to steroids and transfusions, sometimes other treatments are used. Intravenous gamma globulin treatment (IVIgG) is an expensive but often effective way to shorten a hospital stay. This treatment binds to auto-antibodies and keeps them from attacking the red blood cells. It also may reduce antibody production by the patient’s body. It helps “win the battle” but is not proven to improve long-term outcomes. Plasmapheresis is another treatment available at a few referral hospitals in the nation, with a similar end result as IVIgG. Other immune suppressive medications such as cyclosporine, mycophenolate, azathioprine, or leflunomide, often started in conjunction with prednisone, take longer for full effect and are most helpful to reduce how much prednisone is given over the long run.

Patients with IMHA have a high risk for development of abnormal blood clots, and pulmonary embolism is actually one of the leading causes of death in these pets. Therefore, it is common to prescribe blood thinners such as aspirin, clopidogrel (Plavix), and/or heparin. A blood thinner is often given as long as the prednisone is given.

Because anemia affects the entire body, gastrointestinal support is often needed, in the form of antacids, anti-nausea medications, and coating agents.

Survival of IMHA is, unfortunately, not 100 percent. Estimates vary, but the author’s experience is that approximately 75-percent survival is expected. Not all pets respond completely to treatment. Others succumb to pulmonary embolism. Rarely, they develop secondary opportunistic infections, such as fungal infections, due to chronic immune suppressive therapy.

Close monitoring is critical after the patient is discharged from the hospital. A patient may need to be rechecked a couple of times a week at first, gradually reducing to once every 2 to 3 weeks. The medications are tapered over time, and usually by 4 to 6 months after diagnosis, the pet is either off medication entirely or is on the minimum dose of medication required to maintain a normal red blood cell level. Relapses can occur, as can other immune-mediated diseases.

In summary, IMHA is a life-threatening but treatable disease, which most but not all patients survive. A thorough evaluation of the patient is needed initially, and most require hospitalization to survive the initial part of the illness. Long term, the pet owner will need to work closely with their veterinarian to adjust medications and watch for relapses.

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