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CANINE HEMOLYTIC ANEMIA
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Immune Mediated Hemolytic Anemia
Autoimmune Hemolytic Anemia
Immune Mediated
Hemolytic Anemia (IMHA)
(Formerly known as autoimmune hemolytic anemia or AIHA)
Immune-mediated
hemolytic anemia is a condition where the patient's immune system
begins attacking its own red blood cells. What occurs on a microscopic
level is that the branch of the immune system that produces antibodies
begins to direct them against the patient's own red blood cells.
The red blood cells become quickly coated with tiny antibody
proteins, essentially marking these red blood cells for destruction.
When the cells circulate through the spleen, liver, and bone
marrow, they are plucked from circulation and
destroyed, a process called extravascular hemolysis. Their
iron is sent to the liver as bilirubin for recycling. The spleen enlarges
as it finds itself processing far more damaged red blood cells than it
normally does. The liver is overwhelmed by large amounts of iron-pigmented
bilirubin and the patient becomes jaundiced.
To make matters worse, these antibodies activate a special
protein system called the complement system. Complement proteins are
able to simply rupture red blood cells if they are adequately coated
with antibodies, a process called intravascular hemolysis. Ultimately,
there aren't enough red blood cells left circulating to bring adequate
oxygen to the tissues and remove waste gases. A life-threatening
crisis has emerged; in fact 20% to 80% mortality (depending on the study)
have been reported with this disease.
Signs You Notice
Your pet is obviously weak. He or she has no energy and has
lost interest in food. Urine is dark orange or maybe even brown. The
gums are pale or even yellow-tinged as are the whites of the eyes. There
may be a fever. You (hopefully) brought your pet to the veterinarian's
office as soon as it was clear that there was something wrong.
The Tests Show Anemia
Part of a general evaluation includes blood testing. If your
pet seemed obviously pale or jaundiced (yellow-tinged), your vet may
run a test right off the bat called a packed cell volume. This test can
be run in most veterinary offices and involves spinning a small amount
of blood in a small glass tube at high speed to separate the red blood
cells from the serum (the blood's liquid phase). By comparing the blood
tube to a chart, it will become obvious if your pet has a low red blood
cell count. If your pet has hemolytic anemia, the serum will be bright
orange instead of its normal off-white color.
The anemia may come up on a full blood panel submitted to
a reference laboratory. These laboratories perform a test called a
hematocrit, which is slightly different from a packed cell volume but
essentially measures the same thing: the percentage of blood volume
made up by red blood cells. This number should be 43 to 59 for dogs
and 29 to 50 for cats.
Anemia is the condition where one's red blood cell count is
low. Anemia can be mild or severe and can represent bleeding, red blood
cell destruction (as in IMHA) or simply lack of red blood cell production.
Once a patient is found to be anemic, it is important to determine why.
The Tests Show Responsive Anemia
Anemia due to poor red blood cell production by the bone marrow
is called a non-responsive anemia. Such anemias are caused by chronic
inflammatory diseases, such as inflamed skin, infected teeth, or other
long standing irritations, or kidney failure, cancers of various types,
or certain drugs (especially agents of chemotherapy).
Normally when red blood cells are lost, the drop in blood
oxygen that results causes hormonal changes leading to increased production
of red blood cells by the bone marrow. These are called responsive anemias
because the bone marrow is responding. Bleeding and immune mediated red
blood cell destruction are both responsive anemias.
There are several ways to determine if the anemia is responsive
or not from the blood panel results. Most blood panels run by reference
laboratories include a portion called a complete blood count, or CBC,
which reviews red blood cell count, size, shape, maturity as well as white
blood cell types and ratios. A patient with a responsive anemia will
have a very active bone marrow. Red blood cells will be released early,
leading to a variety of sizes and redness of red blood cells circulating
in the blood (less mature red blood cells are larger and paler than mature
cells). Further, red blood cell precursors called reticulocytes are released.
These may be thought of as red blood cells so immature they can't truly
be called "red blood cells. If the bone marrow stimulus is especially strong,
red blood cells may be released still containing cell nuclei. *
These findings indicate the anemia is responsive, which means
either that red blood cells are being lost via bleeding, possibly
internal bleeding, or they are being destroyed by the immune system.
Which Is it?
The Tests Suggest Immune Mediated Destruction Rather
Than Bleeding
There are several clues in blood testing that tell us if our
patient is bleeding or destroying red blood cells.
Icterus (Jaundice)
This is the yellow color that is taken up by a patient's tissues
when the liver is overwhelmed with bilirubin, the iron that contains
by-products of red blood cell destruction. Normally red blood
cells are removed from the circulation when they become old and inflexible.
Their iron is recycled in the liver. With so many red cells being destroyed,
the liver is overwhelmed and bilirubin (a yellow pigment) spills out everywhere,
coloring urine, gums, skin, and the eyes orange.
Is immune mediated red cell destruction the only cause of
icterus? Absolutely not. Liver failure also leads to icterus when
the diseased liver cannot process normal amounts of bilirubin. In cats
especially, bacterial endotoxin (the toxic cell walls of certain types
of infecting bacteria) can lead to icterus. Usually, however, a responsive
anemia together with icterus suggests immune-mediated red cell destruction.
Spherocytes
Spherocytes are red blood cells produced when a red
blood cell is not completely removed by the spleen. The spleen cell
"bites off" only a portion of the red cell, leaving the rest to escape
back to the circulation. In the adjacent graphic, the arrow points to
a spherocyte. Note its uniform dense red color, as opposed to the normal
red blood cells without a dense red color.
A normal red blood cell is concave on both sides and disc-like
in shape. It is slightly paler centrally than on its rim. After a portion
has been bitten off, it re-shapes into a more spherical shape with
a denser red color. The presence of spherocytes indicates that red blood
cells are being destroyed.
Autoagglutination
In severe cases of immune mediated hemolytic anemia, the immune
destruction of red cells is so blatant that the red cells clump together
(because their antibody coatings stick together) when a drop of blood
is placed on a microscope slide. Imagine a drop of blood forming not
a red spot but a yellow spot with a small red clump inside it. This finding
is especially foreboding.
Leukemoid Reaction
Classically, in IMHA the stimulation of the bone marrow is
so strong that even the white blood cells lines, which have very little
to do with this disease but which also are born and incubate in the
bone marrow along side the red blood cells, are stimulated. This leads
to white blood cell counts that are spectacularly high.
More Tests Needed
Coomb's Test (also Called a direct antibody test)
This is a test designed to identify antibodies coating red
blood cell surfaces. This test is the current state of the art for the
diagnosis of IMHA but, unfortunately, it is not as helpful as it might
seem. It can be erroneously positive in the presence of inflammation or
infectious disease (which might lead to harmless attachment of antibody
to red cell surfaces) or in the event of prior blood transfusion (ultimately
transfused red cells are removed from the immune system). The Coomb's
test can be erroneously negative for a number of reasons as well. If the
clinical picture fits with IMHA, often the Coomb's test is skipped.
Remember, not all causes of hemolysis (red blood cell destruction)
are immune-mediated. Onions in large amounts (and possibly garlic
as well) will cause a toxic hemolysis. Zinc toxicity, usually from swallowing
a penny minted after 1983, or from licking off a zinc oxide ointment
applied to the skin, will cause hemolysis as well. In a young animal,
a genetic red blood cell malformation might be suspected.
Once the diagnosis of immune mediated hemolytic anemia has
been made, efforts to determine an underlying cause should be made.
Radiographs of the chest and abdomen to look for tumors are a good idea
especially in middle-aged or older patients. Blood tests to rule out tick-borne
blood parasites such as Ehrlichia and Babesia may be in order depending
on the geographic area where your pet has been living or has traveled.
Treatment And Monitoring During The Crisis
A patient with IMHA is often unstable. If the hematocrit has
dropped to a dangerously low level then blood transfusion is needed.
It is not unusual for a severely affected patient to require many transfusions.
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.
We will review these aspects of therapy.
Transfusion
There are several products that may be helpful in treating
IMHA. If the patient is in a crisis and needs immediate therapy, artificial
blood may be a good choice. Artificial blood (Oxyglobin®) is made
from hemoglobin harvested from cow's blood. Because the patient does not
receive actual red blood cells, the artificial blood does not further stimulate
the immune system. Artificial blood does not require refrigeration and is
likely sitting on the shelf ready to use at your veterinarian's office. The
disadvantage of artificial blood is that it does not last in the body like
a well-matched blood transfusion does. The body begins removing artificial
blood immediately so that the entire transfusion is probably gone in 48
hours or so. In IMHA, this may buy some time but since IMHA tends to have
a long treatment course, it is likely that the patient will be back where
they started from at that point. If a compatible donor is not readily available,
sometimes an artificial blood transfusion buys enough time to find a compatible
donor.
Well-matched whole blood or packed red cells (a unit of whole
blood with the plasma mostly removed leaving only a concentrated solution
of red blood cells) may last longer. Compatible blood can last a good
3 to 4 weeks in the recipient's body. The problem, of course, with IMHA
is that even the patient's own red blood cells are being destroyed so
what chance do donated cells have? Cross matching of red cells is ideal
but still may not lead to a good match given the hyperactivity of the patient's
immune response. For this reason, it is not unusual for several transfusions
to become necessarily in the treatment of this condition.
Immune Suppression
Corticosteroid hormones in very high doses are the corner
stone of immune suppression. Prednisone and dexamethasone are the
most popular medications selected. These hormones are directly toxic
to lymphocytes, the cells that produce antibodies. If the patient's
red blood cells are not coated with antibodies, they will not have been
targeted for removal so stopping antibody production is a very important
part of therapy. These hormones also suppress the activity of the Reticuloendothelial
cells that are responsible for the removal of antibody-coated red cells.
Corticosteroids may very well be the only immune suppressive
medications the patient needs. The problem is that if they are withdrawn
too soon the hemolysis will begin all over again. The patient is likely
to be on high doses of corticosteroids for weeks or months before the
dose is tapered down and there will be regular monitoring blood tests.
Expect your pet to require steroid therapy for some 4 months; many must
always be on a low dose to prevent recurrence.
Corticosteroids in high doses produce excessive thirst, re-distribution
of body fat, thin skin, panting, predisposition for urinary tract
infection and other signs that constitute Cushing's Syndrome. This
is an unfortunate consequence of long-term steroid use but in the
case of IMHA, there is no way around it. It is important to remember
that the undesirable steroid effects will diminish as the dosage diminishes.
More Immune Suppression
If no response at all is seen with corticosteroids, supplementation
with stronger immune suppressive agents is necessary. The two most
common medications used in this case are: azathioprine and cyclophosphamide.
These are very serious drugs reserved for serious diseases. Please follow
the links above to read more about specific side effects concerns etc.
Cyclosporine is an immune-modulator, made popular in
organ transplantation technology. It has the advantage over the two
above medications of not being suppressive to the bone marrow cells.
It has been a promising adjunctive therapy in IMHA but has two major
problems: first, it is extremely expensive and second, blood level monitoring
is necessary to ensure that the dosage is appropriate. This adds dramatically
to the expense of treatment but ultimately may provide the results
not possible with other drugs.
Leflunomide is a new immuno-modulator that is meant for
patient with immune mediated diseases when corticosteroids either
do not work or cannot be used. It is expensive (approximately $600
per month) but we may be hearing more about it in the future.
Human gamma globulin transfusion is a treatment that
is reserved for patients for whom more traditional methods of immune
suppression have been ineffective. The gamma globulin portion of blood
proteins includes circulating antibodies. These antibodies bind the
reticuloendothelial cell receptors that would normally bind antibody-coated
red blood cells. This prevents the antibody-coated red blood cells from
being removed from the circulation. Human gamma globulin therapy seems
to improve short-term survival in a crisis but, unfortunately, availability
of the product is limited and it is very expensive.
Why Did This Happen To Your Pet?
When something as threatening as a major disease emerges,
it is natural to ask why it occurred. Unfortunately, if the patient
is a dog, there is a good chance that there will be no answer to this
question. Depending on the study, 60% to 75% of IMHA cases do not have
apparent causes.
In some cases, though, there is an underlying problem: something
that triggered the reaction. A drug can induce a reaction that stimulates
the immune system and ultimately mimics some sort of red blood cell
membrane protein. Not only will the immune system seek the drug, but
also it will seek proteins that closely resemble the drug and innocent
red blood cells will be consequently destroyed. Drugs most commonly implicated
include penicillins, trimethoprim-sulfa, and methimazole.
Drugs are not the only such stimuli; cancers can stimulate
exactly the same reaction, especially hemangiosarcoma.
Red blood cell parasites create a similar situation except
the immune system is aiming to destroy infected red blood cells. The
problem is that it gets over-stimulated and begins attacking the normal
cells as well.
There is some thinking that vaccination can trigger IMHA.
Insect bites have also been implicated. Both have been temporally
associated with the development of AIHA. The relationship between
recent vaccination and IMHA development is one of the factors that
has led most universities to go to an every 3 year schedule for the
standard DHLPP vaccine for dogs, rather than the traditional annual
schedule.
Breeds predisposed to the development of IMHA include: cocker
spaniels, poodles, Old English Sheepdogs, and Irish setters.
In cats, IMHA generally has one of two origins: Feline Leukemia
Virus infection or infection with a red blood cell parasite called
Hemobartonella felis.
Complications of IMHA
Thromboembolic Disease
This particular complication is the leading cause of death
for dogs with IMHA (between 30% to 80% of dogs that die of IMHA die
due to thromboembolic disease). A thrombus is a large blood clot that
occludes a blood vessel. The vessel is said to be thrombosed. Embolism
refers to smaller blood clots, spitting off the surface of a larger thrombus.
These mini-clots travel and occlude smaller vessels thus interfering with
circulation. The inflammatory reaction that normally ensues to dissolve
errant blood clots can be disastrous if the embolic events are occurring
throughout the body.
Heparin, a natural anticoagulant, may be used in hospitalized
patients (or in patients with predisposing factors for embolism) as
a preventive.
* It should be noted that 4 to 7 days are required for the
bone marrow to generate a response. If hemolysis occurs suddenly there
may not have been adequate time for a response. When this occurs,
if there is any question about the responsive nature of the anemia,
continued monitoring of the complete blood count will show a clear
response in an appropriate time period.
It should also be noted that in an especially unlucky patient,
the red blood cell destruction may extend to the pre-red blood cells
(reticulocytes, nucleated red cells and other precursors) within the
bone marrow. If these cells are also destroyed, the condition is especially
dangerous and it will take weeks rather than days to begin to see a response
to treatment. The lack of circulating immature red cells will lead this
anemia to test as non-responsive.
The 2002 study by Drs. Anthony Carr, David Panciera, and Linda
Kidd at the University of Wisconsin School of Veterinary Medicine reviewed
72 dogs with IMHA looking for trends. Their findings are:
The only predisposed breed they found was the Cocker Spaniel.
Most patients were female.
The mean age was 6.8 years.
Timing of vaccination was not associated with the development
of IMHA.
94% of cases had spherocytes on their blood smears.
42% showed autoagglutination.
70% also had low platelet counts.
77% were Direct Coombs' positive.
58% were suspected of having disseminated intravascular coagulation.
55% required at least one blood transfusion.
Mortality rate was 58%.
Of those that died, 80% had thromboembolism present on necropsy
(autopsy).
Prognostic Factors for Mortality and Thromboembolism in Canine
Immune-Mediated Hemolytic Anemia. A.P. Carr, D. Panciera, L. Kidd.
Journal of Veterinary Internal Medicine. 2002; 16: 504-509.
Another Study
The 2005 study looking for trends, by Drs. Tristan Weinkle,
Sharon Center, John Randolph, Stephen Barr, and Hollis Erb at Cornell
University, reviewed 151 dogs with IMHA. They found:
Cockers spaniels and Miniature Schnauzers were both overrepresented
(i.e., felt to be predisposed). These breeds, however, showed the
same mortality rate as other breeds.
Unspayed female dogs were overrepresented.
Neutered male dogs were more commonly affected than unneutered
male dogs (begging the question of whether male hormones might have
some protective effect).
The chance of survival either long term or short term was
significantly enhanced by the addition of aspirin to the treatment
protocol, especially when combined with azathioprine.
Adequate vaccination information was not obtained for enough
patients to comment on association with vaccination.
89% of affected dogs showed spherocytes on their blood smears.
78% showed autoagglutination.
70% of patients required at least one blood transfusion.
Of the 151 dogs studied, 76% survived, 9% died, and 15% were
euthanized. Survivors were hospitalized an average of 6 days. Non-survivors
were hospitalized an average of 4 days.
100% of dogs that died or were euthanized showed thromboembolism
on necropsy (autopsy).
Of the dogs that survived 60 days or more, 15% experienced
relapse. Most dogs treated with corticosteroids, azathioprine,
and ultra-low dose aspirin did not experience relapse.
Evaluation of prognostic factors, survival rates, and treatment
protocols for immune-mediated hemolytic anemia in dogs: 151 cases
(1993-2002). T.K. Weinkle, S.A. Center, J.F. Randolph, K.L.
Warner. S.C. Barr, H.N. Erb. Journal of the American Veterinary Medical
Association. Vol 226, No 11, June 1, 2005. 1869-80.
Other Websites
IMHA is a very serious disease associated with a high mortality
rate. Sadly, many dogs have succumbed. Several pet owners have used
these sad events to create outstanding informational web sites on IMHA
in tribute and to help others.
Date Published: 3/4/2003 12:43:00
PM
Date Reviewed/Revised:
08/08/2005
Copyright
2005 - 2007 by the Veterinary Information Network, Inc. All rights
reserved.
This work was originally published by Veterinary Information
Network, Inc. (VIN) and is republished with VIN's permission.
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AUTOIMMUNE
HAEMOLYTIC ANAEMIA (AIHA)
IMMUNE MEDIATED HAEMOLYTIC ANAEMIA (IMHA)
There can be several reasons
why a dog may become anaemic (having a depleted number of red blood cells
within the circulation of the blood) i.e. autoimmune disease (or immune
mediated disease), tick borne diseases such as ehrlichia, Babesia and Lyme
disease, cancers, parasites, poisoning (zinc, onions etc), a reaction to
drug administration, hyperthermia, systemic disease. However, primary autoimmune
haemolytic anaemia (AIHA) is the most common, non traumatic cause of anaemia
in the dog, and its incidence is increasing.
This article attempts to outline certain important aspects of the disease
so that clinical signs may be recognised by the owner of an anaemic dog
and aid an early diagnosis and correct treatment of this very serious condition.
GENETIC PREDISPOSITION
Statistics show that AIHA is more common in dogs of young to middle age,
but breeds that are known to be genetically predisposed have, by definition,
an increased susceptibility. Dogs have been known to have AHIA as
young as 3 months, ranging to 12 years of age and over.
TRIGGER FACTOR
AIHA may be triggered by an infection, vaccination, stress, drugs, chemicals,
hormones etc and reports show a higher incidence of AIHA in females, particularly
following a season or whelping. Unfortunately, the owner maybe unaware
of the disease having been triggered until clinical signs appear which,
depending on whether the anaemia
is acute or chronic, may range from only a couple of days, to a few weeks,
or even longer after the ‘trigger’ event.
DISEASE PROCESS
Trigger factors, most of which are unknown, cause the body’s immune system
to react to antigens - proteins that form part of the membrane of the red
blood cell - as if they were foreign invaders.
The immune system is designed to bind antibodies to foreign antigens
and remove them safely from the body. When AIHA occurs, the antigens attach
to the dog’s red blood cells, so when the antigens are destroyed and removed
from the body, so too are healthy red blood cells. Thus resulting in autoimmune
haemolytic anaemia. The body’s immune defence system turns
on itself and the destruction may not stop until all the red cell-bound
antigens are removed from the body.
In some cases the autoantibody is directed against the immature red blood
cells in the bone marrow. This is a severe non-regenerative form
of anaemia. If the correct treatment for AIHA is not given, the dog will
become progressively more anaemic, ultimately it will die.
AIHA can occur in conjunction with other autoimmune diseases such as
Systemic Lupus Erythematosus (SLE), a multi-systemic autoimmune disease,
and Immune Mediated Thrombocytopenia (IMTP) an immune destruction
of the blood platelets (Evan’s Syndrome).
CLINICAL SIGNS - the dog may show some signs of the following:
Weakness
Pale mucous membranes (gums, eyes, genital organs)
Lethargy
Exercise intolerance
Increased breathing rate
Increased pulse rate
Anorexia/weight loss (loss of appetite)
Depression
Bright orange coloured urine
Bright orange coloured faeces
Jaundice (yellow discoloration of mucous membranes)
Fever - low grade
Vomiting
Collapse
Diarrhoea
Craving to eat soil
Occasionally increased drinking and urination
Enlarged spleen, liver, lymph nodes
Skin lesions, including sloughing of skin on the ear tips
Heart murmurs and gallop and other abnormal rhythms
If IMTP is also present - blood blisters on mucous membranes, bruising
and black, tarry stools.
If SLE is also present - joint pain and/or kidney glomerulonephritis
CLASSIFICATION AND DIAGNOSIS
Immune Mediated Haemolytic Anaemia (IMHA) can be either regenerative
or non-regenerative as determined by laboratory examination of a blood sample
and/or bone marrow biopsy.
Regenerative anaemia is characterised by the presence of increased numbers
of large immature red blood cells (reticulocytes) in the circulation.
Non-regenerative anaemia is an anaemia lasting longer that 5 days, with
an appropriately low reticulocyte count in the circulation.
Clinical presentation of AIHA may be acute, subacute or chronic.
Dogs with acute or subacute intravascular haemolytic anaemia (within the
circulation) have a rapid onset of the disease and have little time to
adapt to the depletion of red cells, therefore signs of extreme weakness,
collapse, vomiting, raised temperature and jaundice are often present.
A Coomb’s blood test is performed to check for antiglobulins.
In chronic AHIA it may take weeks or months for clinical signs to show.
This form of AIHA, initially, is very well tolerated and shows minimal,
clinical signs, and the dog can adjust to the slow onset of the disease.
Dogs with chronic AIHA may have episodes of jaundice, collapse,
and show clinical signs that ‘wax and wane’. Eventually, because this form
of AIHA is non-regenerative, (the immature red cells are being made but are
destroyed in the bone marrow by the dog’s own immune system) the dog will
become progressively, more severely anaemic.
Without a bone marrow biopsy it is impossible to distinguish between
non-regenerative AIHA and cancer, or other causes of non-regenerative haemolytic
anaemia. Even in regenerative anaemias, a positive Coomb’s test doesn’t
necessarily prove AIHA or a negative result rule it out.
It appears that some vets’ are not aware that an immune mediated destruction
of the immature red cells can occur in the bone marrow and have wrongly
assumed that cancer of the bone marrow is the cause of the dog’s non-regenerative
anaemia. Usually the prognosis given by the vet is grave, and very
little or no treatment is offered. Surprisingly, very few owners are offered
a bone marrow biopsy for their dog, which could confirm a diagnosis of cancer
or an immune mediated disease.
‘Canine Medicine & Therapeutics’ by Neil Gorman lists six possible
diseases, in the blood analysis section for differential diagnoses for
leukaemia. Five are cancers and the other one is “immune mediated
disease”.
In fact, four out of five categories in the diagnosis of leukaemia, lists
among the differential diagnoses “immune mediated disease”. Despite
this, some vets do not even consider that non-regenerative anaemia COULD
be an immune mediated disease.
In some cases of chronic anaemia, when the dog has become very
anaemic (red cell blood count nearing 12%) the vet has treated the dog
speculatively for AIHA (e.g. based on clinical signs, without a definitive
diagnosis). The alternative to this is that the dog will get weaker
and weaker, as it becomes progressively more anaemic, and eventually has
to be put to sleep to avoid further suffering.
Treating clinical signs without a diagnosis, is not the ideal situation,
but vets do it every day. There are very few conditions that vets
can categorically diagnose on the spot without test results - and
yet it is common practice to give antibiotics or anti-inflammatory drugs,
steroids etc., on the assumption that the dog will improve if treated.
If the prognosis of clinical signs is very poor, but there may be a chance
of survival if the dog is treated appropriately for AIHA, then treatment
should be offered. What is there to lose? Many dogs have been treated
in this way and have responded well, and have survived. If the dog’s red
blood cell count is 12% or less (normal PCV range: 35-55% - in puppies and
certain breeds of dog, this may vary) then a blood transfusion may be necessary
to ‘buy time’ for the drugs to take effect. Early treatment improves
the prognosis of AIHA.
Immunosuppressive drugs are used to treat leukaemia as well as AIHA,
IMTP and SLE, and there is no reason not to treat any dog suspected of
having any of these diseases with high doses of prednisolone, provided a
bacterial, viral or fungal cause of the signs has been ruled out.
RANGE OF TREATMENT FOR AIHA
“In most cases the primary treatment involves immunosuppressive doses
of oral corticosteroid (e.g. Prednisone or prednisolone 2 - 4mg/kg q24hr
divided into twice daily dosing, starting at 2mg/kg and only increase dosage
if response is poor. This should be given for at least 2-4 weeks, and
then if the PCV - Packed Cell Volume
(% of red blood cells within the blood) is stable, decrease to
1mg/kg/24 hours for 2-4 weeks, then 1mg/kg/48hours for another 2-4 weeks,
then gradually taper off. If at anytime the PCV falls, the
veterinary surgeon should return to the previous dose that was working.
A gastroprotectant such as sucralfate (0.5-1g twice a day) should be
given whilst the dog is on high doses of steroids.
In patients with refractory or severe anaemia, cytotoxic/immunosuppresive
drugs such as azathioprine (50mg/Mªq 24h (2mg/kg p/o q24h),
for 1-2 weeks, then every other day, or cyclophosphamide (50mg/Mªp/o
q24h (2mg/kg q 24h) for the first four days of each week for 6-8
weeks, then reassess) should be included in the regime and will eventually
enable a reduced dose of glucocorticoid to be used. Since time is
of the essence, it is advisable to commence these as soon as possible in
those patients with severe disease.
Danazol (synthetic androgen; 5mg/kg p/o q12h). Although Danazol
is usually well tolerated, the drug is expensive and is usually reserved
for patients that are either refractory to a combination of prednisolone
and azathioprine or cyclophosphamide, or intolerant of drug side-effects.
It appears to act synergistically with corticosteroids for the treatment
of AIHA and IMTP, however it is contraindicated in patients who also have
heart, liver or kidney problems.
Cyclosporin (15mg/kg p/o q24h) has been used to treat refractory AIHA.
Supportive therapy (fluids or blood transfusion) may be required in life-threatening
anaemias. A transfusion may ‘buy time’ until therapy becomes effective
(typically 3-7 days). However, the process which destroyed the dog’s
own red cells will rapidly destroy the transfused ones also, if treatment
is delayed. Usually, cross-matched packed red cells only, are preferred
where available. The average circulating life-span of a red blood
cell is approximately 110-120 days.
A splenectomy (removal of the spleen) is usually a last resort in patients
with life- threatening refractory anaemia and should be considered if medical
management is not controlling the disease after 4-6 weeks of therapy.
I hope that the above information will not apply to any of your dogs,
now or in the future. It is only submitted in the knowledge that “awareness
can save lives”.
References:
Linda Aronson DVM, MA
Clinical Immunology of the Cat & Dog - by Michael J Day
Canine Medicine & Therapeutics - by Neil Gorman
Special thanks to Dr. Linda Aronson, for
her support and assistance in the composition of this article.
If you require any further information
please contact:
CIMDA (Canine Immune Mediated
Disease Awareness) jo@cimda.fsnet.co.uk
reprinted with kind permission
from Jo Tucker
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The above information is simply informational.
It's intent is not to replace the advice of a veterinarian nor to assist you
in making a diagnosis of your pet. Please consult with your own veterinarian
for confirmation of any diagnosis. Your pets life may depend on it.