Outsmarting the Saboteur

No one understands why this immune disorder causes the body’s antibodies to mark its own red blood cells for destruction. In severe cases, the lack of circulating red blood cells eventually causes the body to become oxygen-starved — leading to tissue destruction and organ failure.

Blood transfusions, along with heavy doses of corticosteroids and other immunosuppressive agents, have proven to be effective therapy for humans affected by IMHA. But in dogs, it’s a different story: their chances of surviving this immune disorder are only about 40 per cent.

Dr. Anthony Carr, an internal medicine specialist at the Western College of Veterinary Medicine (WCVM), is one of the many scientists across North America who has tried to improve the odds for dogs suffering from this disease. Carr began investigating IMHA when he was a resident at the University of Wisconsin in the early 1990s, and his work has continued at WCVM where clinicians see about 30 cases of canine IMHA every year.

“The sad thing is that nothing has changed since 1994. Some new studies come out, but we still lose just as many dogs.”

The problem, in Carr’s opinion, is that most studies have focused on important but less crucial issues such as outcome, the disease’s risk factors and the potential use of new immunosuppressant drugs.

One of those studies was conducted at WCVM in 2001 when Dr. Astrid Nielssen teamed up with Drs. Carr, Susan Taylor and Marion Jackson. With financial support from the Companion Animal Health Fund, the small study evaluated the use of cyclosporine (a drug often used during human transplants) in combination with two corticosteroids: prednisone and azathioprine.

Since the study only included 12 dogs, Carr says more research needs to be done before scientists determine if the combination of drugs has potential for long-term IMHA therapy. Another limiting factor: more than half of the dogs involved in the study died soon after beginning treatment for the disease— an outcome that mirrors the reality at veterinary clinics across Canada and the U.S.

“Most IMHA dogs die within the first three or four days, and that’s why I think we’re trying to answer the wrong question,” points out Carr. “Instead of finding the best immunosuppressant therapy, we should figure out a way to stop them from dying on us before the corticosteroids and immunosuppressive drugs even get a chance to work.”

What causes most of these dogs to die? Thromboembolism — or small blood clots — is the main killer of dogs diagnosed with IMHA, says Carr, who published an IMHA study with Drs. David Panciera and Linda Kidd in the Journal of Veterinary Internal Medicine in 2002. Searching for the disease’s trends, Carr and his former University of Wisconsin colleagues reviewed 72 cases of canine IMHA. The study had a 58 per cent mortality rate, and of those dogs that died, 80 per cent had blood clots present in their bodies at necropsy. 

 To address the issue of blood clots, several WCVM scientists have been exploring the use of heparin — a naturally occurring compound with anti-thrombotic and anticoagulant effects. This biological product is used to treat conditions like deep vein thrombosis in humans, and veterinarians also give IMHA-affected dogs regular injections of heparin to prevent clot development.

Even so, Carr says scientists don’t entirely understand the drug’s effect on humans — and they know even less about its effect on dogs: “The response is inconsistent from one dog to another, and even in the same animal, you can get an entirely different response from the next injection.”

The variability in injectable heparin dosing, combined with the inconvenience of giving dogs repeated injections, led Carr and graduate student Dr. Mala Sivasankar to develop a CAHF-supported pilot project that tested the potential of using oral heparin in dogs. Their co-investigator was Dr. Linda Hiebert, a WCVM scientist who has used rat models to show that oral heparin is rapidly absorbed and effectively reduces the formation of blood clots without increasing the chances of internal bleeding.

While more work is necessary before scientists can accurately gauge oral heparin’s anti-thrombotic value, none of the dogs involved in the pilot study showed any evidence of bleeding. Those initial results correlate with Hiebert’s previous findings, plus they give Carr hope that oral heparin may emerge as an effective tool in the battle against this self-sabotaging disease.

But for the long term, Carr says it’s crucial for scientists to discover why IMHA causes dogs to clot. Once that mystery is solved, clinicians will be closer to the goals of developing effective therapies and more consistent management practices that will save dogs in those first crucial days.

“Blood clotting is a very rare complication in humans with IMHA. But all dogs with IMHA develop blood clots even though they’re a species that rarely suffers from thromboembolism. So what’s so special about this disease that it makes dogs do something they usually don’t?” questions Carr. “That’s what we need to answer before we can truly manage this disease.”

Reprinted with permission of Vet Topics, publication for the Western College of Veterinary Medicine's Companion Animal Health Fund.
For more information, visit www.cahf.usask.ca