What
is Immune-Mediated Hemolytic Anemia?
Immune-Mediated Hemolytic Anemia (IMHA)
is a serious and often life threatening disorder in dogs and cats.
IMHA results from an inappropriate immune response to the animals
own red blood cells. IMHA
can be classified as primary or secondary.
With primary IMHA, the immune system malfunctions and begins to
treat the red blood cells as if they were foreign invaders and begins to
produce antibodies against the red blood cells.
This response is similar to what would occur against bacteria.
No underlying cause for this inappropriate reaction can be
identified. With secondary
IMHA, an underlying disease condition such as infection, parasites,
cancer or a reaction to a drug or vaccine causes a change in the red
blood cells, which in turn stimulates the immune system to attack the
cells. The antibody
response to the red blood cells can also cause “autoagglutination”,
a condition where the red blood cells stick together like a cluster of
grapes. Autoagglutination
is often associated with clotting disorders including pulmonary
thromboembolism (PTE), which are blood clots in the lungs.
Destruction of red blood cells is termed “hemolysis” and it
can occur within the blood vessels (intravascular hemolysis) or in other
parts of the body, primarily the spleen, liver and bone marrow (extravascular
hemolysis). Intravascular
hemolysis tends to be more severe and carries a worse prognosis than
extravascular hemolysis.
Hemolysis of the red blood cells is very serious, as these cells
are responsible for carrying oxygen to the entire body.
The relative amount of red blood cells circulating in the blood
is measured as the packed cell volume (PCV).
A blood sample is put into a small tube and spun in a centrifuge
to separate the red cells from the liquid portion of the blood and the
white blood cells. The red cells can then be measured. The PCV is an important factor in monitoring patient
improvement or decline.
Who
is at risk?
Both dogs and cats can develop IMHA.
Cats very rarely get primary IMHA, but are more commonly affected
secondarily to underlying diseases such as viral or parasitic
infections. Dogs more
commonly have primary IMHA. Middle
aged, female dogs are at highest risk and certain breeds seem to be over
represented. Cocker
spaniels, English Springer spaniels, Collies, Poodles, Old English
sheepdogs, Irish setters and Dachshunds appear to be at higher risk than
other breeds. More cases of
IMHA are reported to occur in the spring and summer (especially the
months of May and June) than at other times of the year. The reason
behind why age, breed or season plays a role is unclear.
What
are the clinical signs?
The clinical signs of IMHA vary
depending on the severity and type of hemolysis involved.
Clinical signs might be acute or more gradual in onset.
The most common signs include decreased appetite, lethargy, pale
gums and tongue, panting, exercise intolerance and weakness.
These signs are primarily caused by inadequate oxygen delivery to
the body secondary to the decreased PCV.
Vomiting and diarrhea might also occur, but are less common.
The animal may also appear jaundiced.
Breakdown of hemoglobin from the red blood cells results in the
pigment “bilirubin” to circulate in the blood.
This pigment makes the skin and eyes of the animal appear yellow
and the urine might also be a dark yellow or orange in color.
If the hemolysis is occurring rapidly, the urine may appear red.
How
is it treated?
Treatment of IMHA includes supportive
therapy to address the anemia, dehydration and secondary complications
as well as therapy aimed specifically at the disease.
Supportive therapy includes initial stabilization of the patient.
The patient may require one or more blood transfusions to
increase the ability to deliver oxygen to the tissues of the body.
Blood transfusions aren’t without risk.
The immune system is already seeing the animal’s own red blood
cells as foreign and can attack the donors cells as well.
This might initially make the hemolysis worse, although more
recent research suggests this may mot be as severe as we once believed.
Transfusions may also increase the risk of PTE.
It is important to weigh the benefit against the risk, but if the
patient is showing signs that the body is inadequately oxygenated, a
transfusion should be given. Intravenous
fluid therapy is also important to assure the patient doesn’t become
dehydrated and to continually flush the kidneys, as the breakdown
products of hemolysis can do permanent damage to the kidneys.
Specific drug therapy is aimed at suppressing the immune system
in an effort to spare the existing red blood cells and give the bone
marrow a chance to produce new red blood cells.
The cornerstone of drug therapy is corticosteroids, such as
prednisone or dexamethasone. Your veterinarian may also use other drugs in addition to
corticosteroids in attempt to get the disease under control.
Different drug combinations are prescribed on a case-by case
basis, depending on severity of the disease and initial response to drug
therapy. The goal with drug
therapy is to slowly decrease the doses of the medications to a low
level where the immune system is kept in check and the PCV is maintained
in the normal range. Some
patients are able to discontinue drug therapy all together after a
period of time.
What
are the complications?
Complications
associated with IMHA are very serious and can be broken down into those
associated with the disease itself and those that can be attributed to
the drug therapy. The disease itself predisposes the patient to clotting
disorders including PTE or the inability to clot properly. PTE prevents adequate oxygen exchange between the lungs and
the red blood cells and may be fatal.
Disseminated intravascular coagulopathy (DIC) is a condition that
ultimately results in the animal’s inability to clot and may cause
them to bleed abnormally. Other
complications include kidney failure secondary to damage from
hemoglobin, which is released with destruction of the red blood cells.
Drug-related complications are most commonly secondary to
immunosuppression. The
patient is at higher risk for infections, including those caused by
bacteria, fungi and protozoa. In
these cases, infection can quickly spread throughout the body. Another
complication is refractory anemia, where the animal doesn’t respond to
the drug therapy. The drugs, themselves have related side effects.
Corticosteroids can cause gastrointestinal upset and ulceration.
Other chemotherapy drugs used in the treatment of this disease
may cause stomach upset or bone marrow problems.
The goal of therapy however is to use the lowest drug dose that
will control the disease and minimize these side effects.
Any of the above side effects can be detrimental, so close
patient monitoring and frequent blood work are necessary.
