Secondary Immune-Mediated Hemolytic Anemia Can Affect Rottweilers

Immune-mediated hemolytic anemia (IMHA) was the furthest thing from Diane Richardson’s mind when her 2 ½-year-old Rottweiler bitch, Frontier Life Eternal, CGC, seemed uncharacteristically bothered by the 100-degree temperatures of July 2010.

Having owned Rotties for 30 years and bred them for 20 years, Richardson, of Claremont, N.H., sensed something different about her dog’s reaction to the heat that summer. Richardson was about to start competing in rally with the female she called “Bonnie,” a usually healthy, energetic dog.

Bonnie’s condition worsened, and she became very weak. Testing at the veterinary hospital showed she had IMHA and Mycoplasma haemocanis, a blood pathogen transmitted by fleas and ticks.

Not a common condition in Rottweilers, IMHA is a disease in which a dog’s immune system attacks the oxygen-carrying red blood cells, often resulting in severe, life-threatening anemia. It also is referred to as auto­immune hemolytic anemia. Clinical signs include lethargy, decreased appetite, diarrhea, vomiting and jaundice. The amount of jaundice and the level of albumin, or plasma protein, contribute to the likelihood of a dog’s long-term survival.

The mortality rate ranges from 30 to 70 percent, with many dogs dying within the first two weeks of diagnosis. The condition can be expensive to treat due to the cost of diagnosis and medications. Dogs that survive the initial crisis face the risk of relapse and complications related to having a chronically depressed immune system.

Bonnie suffered from secondary IMHA, which occurs along with another disease. Two things may have contributed to her disease: a hornet sting and M. haemocanis. Bonnie spent five days at the veterinary clinic being treated with medications and monitored closely. Her blood work gradually improved, and her appetite returned to normal.

Anthony Carr, Dr.med.vet., DACVIM, professor of small animal clinical sciences at the University of Saskatchewan Western College of Veterinary Medicine in Canada, has studied IMHA for 20 years. “It is a broad term that includes an array of diseases in which the immune system destroys red blood cells,” he says. “It even occurs in dogs with tick-borne diseases.”

Prompt veterinary treatment is the key to stop the destruction of red blood cells, stabilize a dog and allow the red blood cells to regenerate. Blood transfusions may be needed to buy time until medications can work.

Primary & Secondary IMHA

The immune system of dogs with IMHA produces antibodies that attach to oxygen-carrying red blood cells. These antibodies “tag” the red blood cells for destruction by macrophages, or white blood cells.

Although Bonnie had secondary IMHA, the disease also can be primary, or idiopathic, when there is no known cause. Primary IMHA occurs when a dog’s own immune system is the source of the disease. It is thought to be a genetic, or inherited, condition that typically affects middle-aged females and occurs more commonly in some breeds. Affected breeds include the American Cocker Spaniel, Clumber Spaniel, Collie, Dachshund, English Setter, English Springer Spaniel, Irish Setter, and Old English Sheepdog, though it can occur in any breed and at any age.

As IMHA is rare in Rottweilers, Richardson began researching the disease on the Internet to learn more about it. She found forums devoted to autoimmune conditions and started reading about IMHA. “I learned that IMHA is often triggered by an event that independently might be insignificant or harmless,” Richardson says.

Secondary IMHA is caused by a reaction to another illness, medications or toxins. It may occur in dogs battling cancer, such as lymphosarcoma, leukemia and hemagiosarcoma, or when a dog has a blood parasite, such as M. haemocanis and Babesia, that causes an abnormal immune reaction.

In both primary and secondary IMHA, destruction can be extravascular (outside the blood vessels) or intravascular (inside the bloodstream). Extravascular destruction, which may affect the spleen, liver or bone marrow, has a more favorable prognosis because the hemoglobin released by the destroyed cells is engulfed by macrophages, or white blood cells, rather than being released into the bloodstream.

When the destruction is intravascular, the released hemoglobin endangers a dog’s kidney function. Regardless of the site of destruction, massive inflammation results and can affect multiple organ systems. Stroke can result from blood clotting.

In necropsy studies, Carr has found that 80 percent of dogs with IMHA had blood clots in various organs. “Inflammation and hemostasis, the process of clotting to stop bleeding, are definitely linked,” he says. “IMHA is a condition of massive inflammation that promotes hemostasis and the formation of clots.” 

Prompt treatment is important in dogs with IMHA. Laura West, D.V.M., DACVIM, of the Veterinary Specialty Hospital in San Diego, received an AKC Canine Health Foundation grant in 2011 to study new treatments for IMHA. “You have to think of IMHA as being like a snowball rolling downhill,” she says. “By the time the disease is diagnosed, it has already picked up momentum and speed.”

Lethargy is the most common sign of IMHA, as it reflects the anemia and oxygen starvation that results from the destruction of healthy blood cells, West says. Blood in the urine also indicates a breakdown of red blood cells. Jaundice from bilirubin, a byproduct of red blood cell destruction, accumulates and can cause yellowing of the skin and whites of the eyes. The heart can be affected and should the disease continue, a lack of oxygen may cause a dog to collapse.

A series of tests are used to diagnose IMHA. These include complete blood count, blood chemistry analysis, blood smear evaluation to assess the clumping of red blood cells, and a Coombs test to detect antibodies attached to red blood cells. An abdominal ultrasound or radiograph can be used to check for other causes of anemia, such as a tumor.

Veterinarians usually use a three-pronged approach to medications that involves suppressing the immune system, preventing blood clots and treating clinical signs. “For immunosuppression, prednisone is the first line drug used,” West says. “It is very effective but has side effects that can affect a dog’s quality of life, such as excessive thirst and urination, panting, gastro­intestinal ulcers, and increased susceptibility to infections.”

Prednisone therapy may be combined with a second immunosuppressant for better control. Prednisone is a fast-acting medication that successfully suppresses the immune system. By giving a second, slower-acting drug, such as azathioprine or cyclosporine, a dog can be tapered off prednisone sooner. Dogs also may receive low doses of aspirin, heparin or Plavix to help prevent blood clots.

In her study, West evaluated the use of mycophenolate as an alternative drug therapy. The results, which were published in the March-April 2014 issue of the Journal of Veterinary Emergency and Critical Care, showed a significant degree of gastrointestinal toxicity at the dosing level used.

“Today, my typical protocol involves prescribing prednisone, cyclosporine, low-dose aspirin, transfusions, and symptomatic therapies,” West says. “The protocol is tailored to each individual patient based on an assess­ment of that patient and after a frank conversation with the owner regarding the potential cost of treatment. For example, azathioprine could be used instead of cyclosporine to decrease the cost, though it takes longer to have a therapeutic effect.”

Although the ideal treatment for IMHA has yet to be discovered, and is likely to vary on an individual basis, more research is warranted. “Hopefully, we will come to understand the efficacy and the pros and cons of any course of treatment,” West says.

A Polygenic Inheritance Pattern

Primary IMHA, the type dogs inherit, is believed to be a polygenic disease that involves several genes plus environmental triggers. The complexity of a polygenic condition hampers identi­fying causative gene mutations.

Lorna Kennedy, Ph.D., senior scientist at the Centre for Integrated Genomic Medical Research at the University of Manchester in England, and her colleagues have examined the DNA of 325 IMHA-affected dogs in an effort to find the genes responsible for primary IMHA as well as other autoimmune diseases. The work, partially funded by the AKC Canine Health Foundation, identified several areas of interest. 

Although the work is far from complete, Kennedy feels confident primary IMHA is polygenic. “We think that genetics influence whether an animal develops the disease and that there are genes that affect the severity of the disease. It is even more complex because there probably always is an environmental trigger, such as a viral infection.” 

In reality, Kennedy is not confident there will ever be a direct DNA test to identify dogs at risk of developing primary IMHA. “We may be able to develop a series of tests, or one for each gene, that together will allow us to estimate the risk of a particular dog developing the disease,” she says. “I believe that some of the genes responsible for IMHA are common to many breeds, and others are breed-specific.”

Kennedy is continuing her research and is seeking blood samples from dogs of any breed diagnosed with IMHA. (Contact her at lorna.kennedy@ manchester.ac.uk for information.)

In the meantime, she advises breeders to study pedigrees, use a variety of stud dogs and carefully monitor the health of puppies from litters they have bred. Since IMHA usually occurs in middle-aged dogs, this requires monitoring dogs for many years.

For Richardson, her Rottweiler Bonnie rallied, but it was a short-lived experience. Twenty-three days after being treated for IMHA, she again became lethargic. One morning, Bonnie collapsed, and Richardson and her husband rushed the dog to veterinarian, but Bonnie died in her arms before they could arrive.

A necropsy showed Bonnie had a blood clot in her heart, the result of the clumping of blood cells characteristic of IMHA. The experience prompted Richardson to begin a mission to help others whose dogs suffer from IMHA. She devoted a page of her website (frontierrots.com) to Bonnie’s memory and to offer information to others.

“Bonnie’s illness happened so quickly, and before we knew it, she passed away,” Richardson says. “I hope that others will benefit from my experience.” 

Purina appreciates the support of the American Rottweiler Club and particularly Elaine Starry, ARC health coordinator, in helping to identify topics for the Purina® Pro Club® Rottweiler Updatenewsletter.

Known Triggers for Secondary IMHA

Immune-mediated hemolytic anemia may be primary or secondary. When it is primary, there is no known cause. Secondary IMHA occurs secondary to conditions, such as:

  • A reaction to being given medications, such as penicillin, cephalosporins, sulfa drugs, and amiodarone, an anti-arrhythmic agent
  • Exposure to toxins, including zinc from pennies, onions or garlic
  • Bee stings
  • Infections related to pyometra, abscesses and the urinary tract
  • Tick-borne illnesses and leptospirosis
  • Systemic lupus
  • Neoplastic diseases including the cancers lymphosarcoma, leukemia, multiple myeloma and hemangiosarcoma

Source: Shaw N, Harrell K. IMHA: Diagnosing and Treating a Complex Disease. Veterinary Medicine. 2008;103(12):662.

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