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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