Immune-Mediated Hemolytic Anemia Can Occur in Poodles

Though Poodles are not considered a high-risk breed for the autoimmune disease immune-mediated hemolytic anemia (IMHA), the disorder does occur in all three varieties. A devastating, aggressive disease, IMHA causes death in 30 to 70 percent of affected dogs, with many dying within the first two weeks of diagnosis. 

Breeder Leslie Pope-Hall of Black Tie Standard Poodles in Ocala, Fla., recalls the night her 6-year-old bitch “Gracie” sought her out for comfort. “She climbed into my lap with her tail down,” she says. “I looked into her eyes, and they were jaundiced. When I checked her gums, they were pale.” 

The next morning, Pope-Hall took Gracie to the veterinarian. By then, the Standard Poodle was lethargic, had blood in her urine and a runny nose, and a heart murmur was detected. Blood tests confirmed she suffered from IMHA. 

“I had no experience with this disease,” Pope-Hall says. “I bought Gracie to incorporate her pedigree into my bloodline. I had her health tested before I bred her, and her sire and dam had their health clearances. Gracie’s first litter had produced healthy puppies.” 

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. This condition is sometimes referred to as autoimmune hemolytic anemia (AIHA), which should not be confused with other autoimmune conditions such as Addison’s disease, sebaceous adenitis, systemic lupus and certain forms of inflammatory bowel disease. 

In dogs with IMHA, dangerous blood clots are not uncommon. Lethargy is the most common sign, reflecting anemia and the oxygen starvation that occurs as healthy red blood cells die. Decreased appetite, vomiting, diarrhea and jaundice also are signs. 

Dogs that survive the initial crisis, such as Gracie experienced, face the risk of relapse and complications related to having a chronically depressed immune system secondary to the medications used to manage the disease. The amount of jaundice and the level of albumin, or plasma protein, contribute to the likelihood of a dog’s long-term survival. 

Two types of IMHA are recognized. Primary IMHA, the type that may be influenced by genetic factors, is idiopathic or has no known cause. This type can be trigged by an immune reaction following vaccination. It commonly occurs in middle-aged females. Among the breeds considered at risk are American Cocker Spaniels, Clumber Spaniels, Collies, Dachshunds, English Setters, English Springer Spaniels, Irish Setters, and Old English Sheepdogs. Poodles are included in some studies. Secondary IMHA occurs along with another disease, such as cancer, or when a dog has a blood parasite, such as Babesia, that causes the abnormal immune reaction. 

A Complex Polygenic Disease 

Genetic research to identify the gene mutations for IMHA is under way at the University of Manchester in England. Partially funded by an AKC Canine Health Foundation grant, Lorna Kennedy, Ph.D., senior scientist at the Centre for Integrated Genomic Medical Research, and her colleagues have examined the DNA of 328 IMHAaffected dogs. Five Poodles — two Standards, two Toys and one unspecified — are represented in the sample. 

IMHA is likely a polygenic disease influenced by several genes and possibly unknown environmental factors, Kennedy says. Some genes responsible for IMHA are common to many breeds and others are breed-specific, she believes. 

“We think that genetics influence whether an animal develops the disease, but there also are genes that affect the severity of the disease,” Kennedy says. “It is made even more complex because there are likely unknown environmental triggers.” 

The complex genetic interactions causing IMHA in dogs mean there may never be a genetic test for the disease. “We may be able to develop a series of tests for each gene that altogether will allow us to estimate the risk of a particular dog developing the disease,” says Kennedy. 

Education is a key part of reducing disease prevalence. “We need to educate breeders to understand what a risk estimate means,” Kennedy says. “We also want them to understand why they can or cannot use such animals in their breeding programs.” 

The most effective way to reduce IMHA is through the careful selection of breeding partners. Breeders are encouraged to study pedigrees, use a variety of stud dogs and carefully monitor the health of puppies they produce. Since IMHA typically occurs in middle-aged dogs, this requires monitoring dogs for years. 

Disease Process & Treatments 

At the University of SaskatchewanWesternCollege of Veterinary Medicine in Canada, Anthony Carr, Dr.med.vet., DACVIM, professor of small animal clinical sciences, has been studying IMHA for about 20 years. “IMHA is a broad term that includes several diseases in which the immune system causes destruction of red blood cells,” he says. “The destruction can be extra-vascular, or outside the blood vessels, or intravascular, inside the bloodstream.” 

Dogs with extravascular disease in which the red blood cells are destroyed in organs such as the spleen, liver or bone marrow generally do better than those with intrasvascular disease. In organs, the hemoglobin released by the destroyed cells is engulfed by macrophages rather than being released into the bloodstream, where it can endanger renal function. 

Baljit Singh, BVSc, Ph.D., professor at the Western College of Veterinary Medicine, and his colleagues are examining the lung changes that occur in dogs with IMHA. In studies of dogs with IMHA that died or were euthanized, 80 percent had blood clots. 

“We want to know why dogs with IMHA experience blood clotting when dogs rarely develop blood clots,” he says. “Macrophages are present in huge numbers in these dogs’ lungs and other organs. This isn’t normal.” 

Research into novel ways of treating IMHA may offer hope. Laura West, D.V.M., of the VeterinarySpecialtyHospital in San Diego, has received an AKC Canine Health Foundation grant to determine new treatment protocol. “You have to think about IMHA like a snowball rolling downhill,” West says. “By the time we have diagnosed the disease, it already has picked up momentum and speed.” 

Jaundice, which many dogs experience, is caused by the accumulation of bilirubin, a byproduct of the red blood cell destruction that occurs. It is noted in the yellowing of the skin and the whites of the eyes. Blood or excessive bilirubin in the urine indicates the breakdown of red blood cells. The heart also may be affected, such as the heart murmur Gracie experienced. Typically, a heart murmur is secondary to the severe anemia and not primary heart disease. If the disease continues unchecked, a dog may eventually collapse due to a lack of oxygen for bodily functions. 

Once signs are observed, a diagnosis is determined based on a complete blood count, blood chemistry analysis, blood smear evaluation of the clumping of red blood cells and a direct Coombs’ test to determine whether antibodies are attached to red blood cells. Occasionally, a veterinarian will conduct an abdominal ultrasound or perform an X-ray to check for other causes of anemia or ingested zinc. 

“Prompt veterinary treatment is crucial,” West says. “Waiting to see if the signs disappear can be fatal. The goal is to stop the destruction of red blood cells, stabilize the dog and allow red blood cells to regenerate.” 

Not uncommonly, a dog may need a blood transfusion. “A transfusion buys time for the medications to work,” says West. 

Medications are prescribed using a three-pronged approach that includes suppressing the immune system, preventing blood clots and treating signs such as vomiting and diarrhea. Veterinarians often prescribe prednisone along with a second drug for immunosuppression. 

“Theoretically, this allows for better control,” West says. “Prednisone acts faster to suppress the immune system, and the addition of a second, slower acting drug, such as azathioprine, allows the dog to be tapered off prednisone quicker.” 

Prednisone can have side effects that affect a dog’s quality of life. These include excessive thirst, urination, panting and gastrointestinal ulcers. Susceptibility to infections is another possible effect due to the immunosuppression. 

West is studying the use of mycophenolate as an alternative to azathioprine, a drug used in humans to prevent rejection after organ transplants. “With IMHA, the truth is that we don’t know the ideal treatment protocol,” she says. “Other drugs have been evaluated in the past without significant evidence to support one over another. Early results of mycophenolate are promising. Though it also is used as an anti-transplant rejection drug in humans, and in treatment for autoimmune diseases, it seems to produce the desired remission. Treatable diarrhea is the main side effect.” 

Quick Diagnosis Aids Outcome 

Joan Harrigan of Phippsburg, Maine, had an experience similar to the one Pope-Hall had with Gracie when her 2-year-old brown Standard Poodle “Saoirse” was diagnosed with IMHA. “In a day, Saoirse went from being one of the healthiest dogs I have ever owned to the sickest,” Harrigan says. “She was fine in the morning, but when I came home, Saoirse didn’t even get up to greet me. She wasn’t interested in food, and the next morning, she just looked sick, even her coat was dull.” 

Harrigan rushed her Poodle to a veterinary referral clinic in Scarborough, Maine. A complete blood count test confirmed a diagnosis of IMHA. Saoirse’s white blood cell count was elevated, and clumps of red blood cells were seen in the blood smear evaluation. Pale gums, dull eyes, low-grade temperature, an enlarged spleen and cervical lymph nodes were among the signs of IMHA. 

Saoirse was admitted to the veterinary specialty hospital, where she was given oxygen, two immunosuppressives — prednisone and azathioprine — and an antibiotic. “We were fortunate,” Harrigan says. “Saoirse didn’t need a transfusion and was only in the hospital one day. When I visited her the next morning, she had been weaned off the oxygen and looked much better. She readily ate some chicken for me, so I was able to take her home and keep her quiet. She rebounded quickly.” 

Follow-up blood work showed steady improvement. As the azathioprine began to work, the prednisone dose was lowered and then eliminated. Seven months later, “you’d never have known Saoirse had been ill,” Harrigan says. “I continue to watch her carefully for signs of infection or any change in her appearance or energy. We do blood work every few months. Her recent tests were great, though her white blood cell count was on the low end of normal.” 

The white blood cell count prompted the veterinarian to reduce the azathioprine from three doses a week to two. The drug can cause pancreatitis and gastrointestinal upsets and suppress the bone marrow. Saoirse experienced secondary infections from the immunosuppression. The goal is to allow her marrow to recover between doses and ultimately wean the dog from the medication altogether. 

Though Saoirse was younger than average when she developed IMHA, her life expectancy is two to three years past the diagnosis. “Saoirse will likely die before she is 6 years old,” Harrigan says. “I enjoy every day that I have with her, but this truly is a devastating disease.” 

After Pope-Hall’s Standard Poodle, Gracie, was given a blood transfusion and medications that included prednisone, the dog rallied and Pope-Hall took her home. “She came in wagging her tail and ate dinner,” she says. “The next day, her condition was no better, and we were back to square one.” 

Eventually, Gracie was euthanized. “It was a difficult decision, but the only right one,” Pope Hall says. “She was just so sick.” 

Though answers about the genetics of the IMHA, why dogs develop blood clots, and the best treatment protocols are slow coming, Carr, the researcher who is studying blood clots, is optimistic. “Too many good dogs have died of this disease,” he says. “We will keep plugging away at it until we know more.” 

Links to 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 that include:

  • Recent administration of medications, such as penicillin or sulfa drugs
  • Exposure to toxins, such as zinc from pennies, onions or garlic
  • Bee stings
  • Infections such as urinary tract infections and abscesses
  • Tick-borne illnesses
  • Systemic lupus
  • Cancer such as lymphosarcoma, leukemia and hemangiosarcoma.

Source: Shaw N, Harrell K. IMHA: Diagnosing and treating a complex disease. Veterinary Medicine. 2008;103(12):662.

 

Purina appreciates the support of the Poodle Club of America and particularly Elly Holowaychuk, D.V.M., and Leslie Newing, editor of The Poodle Papers, in helping to identify topics for the Purina Pro Club Poodle Update newsletter.

 

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