Immune‐Mediated Haemolytic Anaemia in Dogs

Every time I attend a conference, the lectures on immune‐mediated haemolytic anaemia (IMHA) are among the best attended. That’s because there’s almost no other common disease of dogs that makes vets feel so powerless.

This page is a summary of two recent consensus statements from the American College of Veterinary Internal Medicine. It puts together the best of what we know into one guideline on diagnosis and treatment. Most importantly, it’s written in a way that dog owners can understand.

What Is IMHA?

Haemolysis is the rupturing and destruction of red blood cells. It has many causes, including cancer, genetic faults, blood parasites and toxins like zinc. However, the most common type in dogs is an autoimmune disease.

Immune-mediated haemolytic anaemia occurs when antibodies are made that attach to the surface of red blood cells. This starts an immune cascade that ends with their destruction or removal. You can think of the antibodies as a label that says, “kill this enemy”.

By its very definition, we don’t call it IMHA until the destruction is severe enough that the dog becomes anaemic (has too few red blood cells). These dogs show the classic signs of anaemia:

  • Lethargy
  • Panting
  • Pale gums

The red cell destruction also releases lots of blood pigments that we sometimes also see as:

  • Red or dark yellow urine
  • Yellow eyes, gums and skin (called jaundice)

(Just a quick word on spelling: haemolytic and anaemia are English/Australian spellings and mean exactly the same as hemolytic and anemia.)

Causes Of IMHA

Despite many theories, nearly all cases of IMHA have no known cause. It seems to develop ‘out of the blue’ without any identifiable trigger.

Occasionally, it can appear after a vaccination, but as so many others do not, no link has been proven. The best evidence is for a link in some dogs with a blood parasite called Babesia. We also see haemolytic anaemia in association with certain cancers, and sometimes after using certain drugs.

In 25 years, I have sometimes suspected, but never proven a cause in any dog I have treated.

Diagnosis Of IMHA

IMHA has a fatality rate approaching 50%, so it’s important to start treatment as soon as possible. However, as treatment causes severe side effects, it is also important that the diagnosis is accurate.

The first step is a physical exam at the vet with blood and urine testing including a blood film examination. Read more about blood tests and urine tests at these links.

Testing should show anaemia, plus at least one of the following signs of red cell destruction:

  • Spherocytes (abnormal small, round red cells caused by partial destruction)
  • High blood bilirubin (caused by release of red cell pigments)
  • Strong positive bilirubin on a urine test
  • Red urine or red serum caused by free haemoglobin
  • Ghost cells (remnants of destroyed red cells)

To confirm the diagnosis, at least two of the following biomarkers of IMHA should also be positive:

  • Saline agglutination test (SAT)
  • Direct antiglobulin or Coomb’s test (DAT)
  • Flow cytometry (FC)

In practice, most vets will start treatment while waiting for these later tests, which also aren’t as clear-cut as we would hope. Therefore, confirmation of the diagnosis also relies on a favourable response to treatment.

Early Treatment of IMHA in Dogs

If not already done, the first step is searching for possible triggers, by screening:

  • Vaccination history
  • Travel
  • Exposure to fleas and ticks
  • Heartworm exposure
  • Toxins (e.g. zinc coins if used in your country)
  • Blood parasites in certain affected areas (not Adelaide)

An abdominal ultrasound for cancer is also worthwhile especially if treatment is not quickly successful.

Then, the mainstay of treatment is immune suppression by prednisolone at an initial oral dose of 2‐3 mg/kg/day, either given at once or split into two doses.

These are very high doses, and will inevitably cause severe side effects that you can read about here. For this reason, if the starting dose of prednisolone is over 2 mg/kg/day, it is a good idea to decrease to under 2 mg/kg/day within the first 1‐2 weeks, provided the dog is responding to treatment.

Most vets will add a second line treatment to reduce the amount of prednisolone needed. This can be either:

  • Azathioprine (generally well-tolerated, but can cause side effects of nausea, vomiting, and diarrhoea, and very rarely liver or bone marrow damage)
  • Cyclosporine: (the only one that’s a registered dog medicine; read about the dose & side effects of Atopica here)
  • Mycophenolate (also generally well-tolerated with occasional gastrointestinal side effects)

There is no evidence to help in choosing between these drugs, but only one should be used.

Later Treatment of IMHA

Reductions in the dose of prednisolone can occur when:

  • The anaemia has remained stable or improved for at least 2 weeks
  • The packed cell volume (PCV or haematocrit) is over 30%
  • Spherocytes or ghost cells have decreased
  • Agglutination, serum bilirubin, and signs of red cell regeneration have all reduced

At this stage is is appropriate to decrease the dose of prednisolone by 25% every 3 weeks as long as there is no relapse. Each time, this should be confirmed by a blood test plus an occasional urinalysis.

Generally, the dose of the second drug (if used) is not changed, other than a single reduction in azathioprine to every second day after 2-3 weeks. Dog owners can expect that a successful dog could stay on prednisolone for 3‐6 months, and the second drug for 4‐8 months.

Other Medications

A major risk for dogs with IMHA is pulmonary thromboembolism, especially in the first few weeks. This is when a blood clot forms in the lungs. Therefore, it is a good idea to treat IMHA dogs with either:

  1. unfractionated heparin,
  2. low‐molecular‐weight heparin, or
  3. factor Xa inhibitors

Blood transfusions are often necessary in the first few weeks. Packed red blood cells are ideal, but most dogs only have access to whole blood and this is perfectly adequate. The aim is to keep the anaemia from being life threatening while awaiting immune suppression. Most vets transfuse when the PCV or haematocrit drops to 12%.

Protection of the gut lining is also a good idea as high prednisolone doses can cause stomach ulcers. Generally we will use a proton pump inhibitor such as omeprazole if the risk exists.

Other drugs are only given based on the individual patient. Splenectomy (removal of the spleen) is no longer considered an effective treatment.

To finish, it’s important to be realistic about the survival chances of any dog with IMHA. It’s a distressing and frustrating disease with a high mortality rate even with the best of care. No owner or vet should feel responsible if their dog fails to survive such a devastating illness.

By Andrew Spanner BVSc(Hons) MVetStud, a vet in Adelaide, Australia. These blogs are from a series regularly posted on email and Twitter. Subscribe via email here to never miss a story!
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Further Reading

ACVIM consensus statement on the diagnosis of immune‐mediated hemolytic anemia in dogs and cats

ACVIM consensus statement on the treatment of immune‐mediated hemolytic anemia in dogs

Andrew

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