Immune-mediated hemolytic anemia

Friday, February 01, 2008

By Stefanie Worwag, DVM
Internal Medicine Dept.
Garden State Veterinary Specialists

Immune-mediated hemolytic anemia (IMHA) is one of the most common types of anemia in small animals. Anemia means a decreased amount of red blood cells. Red blood cells bring oxygen to and remove waste from all areas of the body. Immune-mediated hemolytic anemia is a condition where the patient’s own immune system is destroying its own red blood cells. Cells from the immune system produce antibodies that coat the red blood cells and mark them for destruction. In primary (idiopathic) IMHA, no underlying cause of this disease is found. IMHA can also occur secondarily to an infection, blood parasites, and cancer or drug/toxin exposure.

In most cases, the abnormal red blood cells are cleared by the liver and spleen (extravascular hemolysis). Iron contained within the red blood cells is sent to the liver as bilirubin to be recycled. Bilirubin leaks out and settles in tissue which can be noticed by yellow gums, yellow around the eyes and orange colored urine and the patient becomes jaundice. In severe cases, the immune system can destroy the red blood cells within the vessels before reaching liver and spleen which is called intravascular hemolysis. These patients have a port wine colored urine.

The clinical signs that the owner notices at home are initially vague and include lethargy and decreased appetite but they will quickly progress to weakness or collapse due to the low red blood cell count (anemia). Sometimes a pet also will vomit. Within days, you will see pale mucus membranes, yellow around the eyes, and the patient often has an increased temperature. Because the initial signs might be mild, it is always important to bring your pet to the veterinarian to be examined if you notice something abnormal.

What causes IMHA or why did it happen? If the patient is a dog, commonly no apparent reason is found. Depending on the study, 60% to 75% of cases are primary or idiopathic and no known cause is found. In secondary IMHA, the immune system gets stimulated or something changes the red blood cell membrane causing the antibodies to attach. Certain drugs known to do that include sulfa drugs and penicillins. Cancers can do that as well, especially hemangisarcoma. It is also debated that vaccinations may trigger the immune system and possibly insect bites as well. Tick born diseases/blood parasites (Ehrlichia, Rickettsia, Anaplasma, Babesia) are known causes of IMHA.

Breeds predisposed to the development of IMHA include cocker spaniels, poodles, Old English Sheepdog, Irish Setters and Schnauzers with cocker spaniels being over represented the most. Female dogs might be over represented.

IMHA is not as common in cats as in dogs and is often associated with Feline Leukemia Virus infection or infection with the blood parasite Hemobartonella felis (Mycoplasma spp.).

Non immune-mediated causes for hemolysis have to be ruled out such as zinc toxicity. This is most often due to penny ingestion. Acetaminophen, onions, garlic or other oxidant agents can lead to hemolysis. Inherited defects, low blood phosphate levels, and splenic abnormalities can also mimic IMHA.

Certain blood abnormalities that are frequently but not always seen with IMHA include spherocytes. These are red blood cells that were not completely cleared from the spleen and have an irregular appearance. Agglutination, clotting together of the red blood cells, is commonly observed. The anemia is usually regenerative, meaning that the bone marrow is reproducing red blood cells. It can take up to 5 to 7 days for the bone marrow to respond. In some cases, the immune system is also attacking precursor red blood cells in the bone marrow. These animals usually take longer to respond to therapy. Full body screening including thoracic and abdominal radiographs (x-rays) and abdominal ultrasound to look for any cancer or metal foreign body should be done. Blood titers for tick born diseases should be done.

Treatment is directed towards correcting the underlying cause (if present) and to suppress the immune system. The primary choice to suppress the immune system is corticosteroids (prednisone or dexamethasone). Other medications for either long term control or additional medications to modulate the immune system that are commonly used include azathioprine and cyclosporine, among others. In severe cases, human immunoglobulin transfusion is used in attempt to control the red blood cell lysis. The patient has to be supported until the destruction on the red blood cells has been stabilized. Red blood cells carry oxygen to all parts of the body and if not enough red blood cells are available, the organs may become damaged. Patients often require several blood transfusions to replenish red blood cells or transfusions containing artificial compounds that can carry the oxygen throughout the body.

One of the most common complications in this disease process that often leads to death or euthanasia is thromboembolic events. The patient is prone to form little blood clots that will occlude vessels and prevent blood flow. To prevent this, patients are placed on a very low dose of aspirin or receive heparin.

A patient usually shows signs of improvement within 3 to 5 days. However, sometimes it can take over a week to stabilize the destruction of the red blood cells. The prognosis varies depending on the literature and the overall mortality rate for primary canine IMHA is as low as 26% to as high as 70%. And about 15% to 25% of dogs will relapse in the future. Our survival rate is probably about 70%.

IMHA is one of the most common causes of anemia in small animals and can have an overall guarded prognosis. Thromboembolic disease is a common complication. The clinical signs mostly caused by the anemia are lethargy, weakness, decreased appetite and will have an acute onset. It is important to consult with a veterinarian if your pet is not feeling well.

The information contained in this article is for informational purposes only and is not intended to be a substitute for the advice of a veterinarian.

This article is for informational purposes only and should not be used as a substitute for the professional advice of your veterinarian.

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