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Immune Mediated
Hemolytic Anemia
Nancy McDonald RN, BSN
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Immune-mediated hemolytic anemia is a
condition where the patient’s immune system begins to attack its own
red blood cells. Microscopically, the branch of the immune system
that produces antibodies begins to direct them against the patient’s
own red blood cells. Red blood cells become quickly coated with tiny
antibody proteins, essentially marking these red blood cells for
destruction. When cells circulate through the spleen, liver, and
bone marrow, they are plucked from circulation and destroyed, a
process called “extravascular hemolysis.” Iron is sent to the liver
as billirubin for recycling. The spleen enlarges as it is processing
far more damaged red blood cells than it normally does. The liver is
overwhelmed by large amounts of iron-pigmented billirubin, and the
patient becomes jaundiced. To make matters worse, a special protein
system called the “complement system” is activated by these
antibodies. Complement proteins are able to simply rupture red blood
cells if they are adequately coated with antibodies, a process
called “intravascular hemolysis.” Ultimately, enough red blood cells
are not left circulating to bring adequate oxygen to tissues and
remove waste gases. A life-threatening crisis has emerged. Mortality
rates of 20% to 80% have been reported with this disease.
How sick the patient is may depend upon how quickly he is “hit with
it.” The dog is weak, has no energy and has lost interest in food,
may have vomiting and diarrhea; its heart rate and breathing are
rapid. Urine is dark orange to brown. Gums are pale or yellow-tinged
as are the whites of the eyes. Fever could be present; liver and
spleen are enlarged. Obviously, something is terribly wrong.
First, the veterinarian will determine that the pet is anemic by a
test usually run in the office called a packed cell volume or submit
blood to a reference laboratory for a full blood panel. Diagnosis of
IMHA may rely on exclusion of other causes of other hemolytic
anemia, concurrent with certain laboratory findings.
Anemias can be “non-responsive” and “responsive.” “Non-responsive”
anemia is due to poor red blood cell production by the bone marrow
caused by chronic inflammatory diseases (like inflamed skin,
infected teeth, or other long standing irritations), kidney failure,
cancers of various types, or certain drugs, (especially agents of
chemotherapy). Conversely, in “responsive anemia”, bone marrow
production increases due to loss of red blood cells and lack of
blood oxygen. Both bleeding and immune-mediated red blood cell
destruction are “responsive anemias.” By looking at results of the
“complete blood count” or “CBC” on the blood panel from the
reference lab, it can be determined if the anemia is responsive or
not. With responsive anemia, it has to be determined if red blood
cell loss is due to bleeding, possibly internal, or are they being
destroyed by the immune system.
Once again, several clues from the blood panel tell if a patient is
bleeding or destroying red blood cells. One of these clues is
“icterus” or “jaundice”. Bilirubin is iron left after a red blood
cell has been destroyed. Normally red blood cells are removed from
circulation when they become old. Iron is recycled in the liver.
When the liver is overwhelmed with large amounts of bilirubin (a
yellow pigment), it spills out everywhere, coloring urine, gums,
skin and eyes orange. Icterus can also result from liver failure
when the diseased liver cannot process normal amounts of bilirubin.
However, a responsive anemia together with icterus, suggests
immune-mediated red cell destruction.
Presence of special red blood cells called spherocytes is another
clue found in the blood panel. Spherocytes are produced when the
spleen does not completely remove a red blood cell. The spleen takes
a bite out of the red blood cell and it reshapes and changes color
thus indicating that red blood cell destruction is taking place.
Autoagglutination occurs in severe cases of immune-mediated
hemolytic anemia when the immune destruction of red cells is so
blatant that red cells clump together (because their antibody
coatings stick together) when a drop of blood is placed on a
microscope slide. This finding is especially foreboding.
Also, the blood panel of immune-mediated hemolytic anemia will show
a “leukemoid reaction,” a high white cell count. In immune-mediated
hemolytic anemia, the stimulation of the bone marrow to produce red
blood cells is so strong that even the white blood cell lines are
stimulated.
A state of the art blood test to identify antibodies coating red
blood cell surfaces is called “Coomb’s”test, also called a “direct
antibody test.” However, this test is not very accurate in dogs.
Recently, the Kansas State University College of Veterinary Medicine
developed a new test that will accurately identify those dogs with
the disease. As of this writing, the test is not available
commercially; blood samples taken from a dog suspected of having
IMHA must be sent to Kansas State University’s special laboratory to
be tested.
With a diagnosis of immune-mediated hemolytic anemia, efforts should
be made to determine an underlying cause. With primary disease, the
process is spontaneous with no identifiable trigger (the immune
system targets normal blood cells). Other possible causes or
triggers are drugs (penicillin or sulfonamides), tick born parasites
(Erlichia and Babesia), viruses or bacteria. Recent observation has
led to consideration that vaccination can trigger IMHA, which has
led to most universities recommending a 3 year schedule for standard
DHLPP vaccines, breaking them down to Core and Non-Core vaccines,
based on specific criteria. Certain breeds, primarily spaniels,
poodles and setters, are predisposed to develop the disease, though
it can occur in any breed of dog. It can also manifest as part of
other immune-mediated diseases as they attack multiple organs
concurrently, especially systemic lupus erythematosus or rheumatoid
arthritis.
Treatment of choice is to suppress the immune system using high
doses of corticosteroid hormones. These hormones are directly toxic
to lymphocytes, cells that produce antibodies. If the patient’s red
blood cells are not coated with antibodies, they will not be
targeted for removal so stopping antibody production is very
important. Corticosteroid hormones also suppress the activity of
cells that are responsible for removal of antibody-coated red cells.
Corticosteroids may be the only immune suppressive medications the
patient needs. It is likely the patient will be on a high dosage of
corticosteroids for weeks or months before the dose is tapered down.
If the drug is withdrawn too soon, hemolysis will begin all over
again. Sometimes a patient must always be on a low dose to prevent
recurrence. Unfortunately, severe and dangerous side effects are
associated with long-term steroid use. However, in the case of
immune-mediated hemolytic anemia, there is no way around it. It is
important to remember that undesirable steroid effects will diminish
as the dosage diminishes.
Some dogs do not respond to corticosteroid treatment and require
more potent immunosuppressive drugs that are often combined with
corticosteroid treatment. These cytotoxic agents are commonly used
in chemotherapy to inhibit cell division and can produce severe side
effects. Other treatments used are immune-modulator drugs used in
organ transplantation and human gamma globulin transfusions. These
are extremely expensive, adding greatly to the cost of treatment.
The patient with IMHA is often unstable. General supportive care is
needed to maintain the patient’s fluid balance and nutritional
needs. Most importantly, the hemolysis must be stopped by
suppressing the immune system’s rampant red blood cell destruction.
If red blood cell levels get dangerously low, blood transfusions are
needed to buy time until treatment becomes effective. Well-matched
whole blood or packed red cells are ideal. With IMHA, the patient’s
own red blood cells are being destroyed as well as the transfused
red blood cells. Consequently, it is not unusual for a severely
affected patient to require many transfusions. Artificial blood and
bovine blood are available although neither last long in the body.
A leading cause of death for dogs (between 30-80%) is due to
thromboembolic disease when mini-clots travel through the body and
occlude smaller vessels thus interfering with circulation. Heparin,
a blood thinner, may be used in hospitalized patients as a
preventive.
Presently, IMHA carries a guarded prognosis, particularly when
multiple body systems are affected, but veterinary researchers are
investigating new methods of treatment. If your dog has been
diagnosed with IMHA, be prepared for a long and emotionally draining
battle knowing that with your support and the hard work of your
veterinarian, you can make its days more comfortable.
References:
Vetcentric.com,
PetEducation.com,
Vet.cornell.edu,
Cloudnet.com, Merck Veterinary Manual,
Marvistavet.com
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