Canine Autoimmune Hemolytic Anemia
A disease characterized by
increased destruction of red blood cells (erythrocytes) by the dog's own
immune system, canine autoimmune hemolytic anemia (AIHA) is one of the most
common blood (hematologic) disorders affecting canines. Though much
attention has been given recently to AIHA due to evidence linking the
process of vaccinating with the manifestation of this sometimes
life-threatening disease, immunization is only one potential cause for this
condition. The following article provides a detailed explanation of AIHA in
terms of the disease process, diagnosis and treatment, and explores factors
that may play a role in the development of this disorder in the canine.
The Blood: A Brief Overview
The blood is considered an
organ having its own complex and diverse development, structure and
functions. Its unique form, cellular tissue suspended in fluid plasma,
allows it to serve as a main distribution system throughout the body.
Cellular tissues composing the blood include: the red blood cells, which
provide oxygen to tissues of the body; the white blood cells, which prevent
invasion of microorganisms or other foreign substances; the lymphocytes,
which carry out immune surveillance; and the platelets, which are involved
in keeping the components of the blood in balance. Remarkably, all of these
cellular components originate from a common source called stem cells located
in the bone marrow. These stem cells give rise to a mature colony of cells
which as they continue to divide and mature undergo a series of changes, a
process known as differentiation, and eventually develop into the
specialized blood cells indicated above.
Anemia is a condition brought
on by abnormalities which lead to a deficiency in the number of red blood
cells. Although the average life span of a circulating red blood cell is
brief in most organisms (approximately 4 months), under normal circumstances
the red blood cell mass is maintained at a constant level because new red
blood cells are made as old red blood cells are destroyed and removed from
circulation by the white blood cells. When this balance is disturbed and the
level of red blood cells decrease to a point where the demand exceeds the
capacity of the bone marrow to produce them, anemia develops. Because
integrity and function of other organs in the body are dependent upon red
blood cells to deliver oxygen to their tissues, if the red blood cell number
decreases to a point where the body is unable to compensate for the decrease
in oxygen transport, serious and irreparable tissue and organ damage may
occur. Conditions which may cause a decrease in the circulation of red blood
cells include excessive blood loss (hemorrhage), impaired ability of the
bone marrow to produce new red blood cells, or increased rate of red blood
cell destruction.
Immune-Mediated Hemolytic Anemia
What is AIHA?
AIHA is a disorder in which
the survival of red blood cells is shortened because the dog's immune system
targets and destroys its own red blood cells. This type of immune
dysfunction in which the host develops a reaction to and damages its own
tissues is termed autoimmunity . In most cases, the dog's body will attempt
to compensate for red blood cell loss by increasing production of new red
blood cells. However, if red blood cell loss proceeds at a rate faster than
the rate of replenishment, a condition of life-threatening anemia will
develop.
What causes AIHA
The exact mechanisms which
trigger the dog's immune system to attack and destroy its own red blood
cells are unknown, however, the disease process is believed to occur when
antibodies coat the surface of the red blood cells tagging them for
destruction by the white blood cells. When the body is invaded by an
infectious microorganism or agent, the body produces a number of antibodies
that range in specificity for that particular invading antigen. Some of the
antibodies are highly specific, however, others will bind with less
specificity. In the normal immune system, suppressor T-cells (see
ensure that these non-specific antibodies do not react with normal host
tissues. However, it is believed that some dogs may have poorly regulated
T-cell suppression that allows these non-specific antibodies to attack their
own cells. Such a genetic predisposition for AIHA has been suspected in
several breeds of dogs including Old English Sheep Dogs, Cocker Spaniels,
Poodles, Lhasa Apsos and Shih Tzus. Alternatively, some clinical studies
exploring potential causative mechanisms have identified several non-genetic
factors that may play a role in development of this disease. For example,
the observation that dogs afflicted with AIHA also demonstrated increased
antibody titers to viral antigens for canine parvovirus and distemper virus
suggests that certain viral infections may trigger an autoimmune reaction.
Under such circumstances it is believed that there is adsorption of the
virus to the red blood cell. When the immune system launches anti-viral
antibodies to destroy the virus, these antibodies target and destroy not
only the virus, but the red blood cell as well. Similarly, some drugs (such
as antibiotics, analgesics, cardiovascular drugs, etc.) as well as viral
antigens composing modified-live vaccines are also believed to induce AIHA
through this type of mechanism.
What are the symptoms of AIHA?
Symptoms of AIHA depend on the
severity of the underlying autoimmune reaction which is influenced by the
level of autoantibodies directed at destroying the red blood cells as well
as the efficiency of the white blood cells to target the red blood cells and
the ability of the bone marrow to replenish circulating red blood cells. In
cases of acute hemolytic anemia, the dog may experience fever, depression,
weakness, fatigability , and pallor of the mucus membranes. In some cases,
the spleen may be noticeably enlarged.
How is AIHA diagnosed?
Because hemolytic anemia can
occur as a symptom of a number of diseases such as infections, cancer, and
other underlying autoimmune disorders (eg. systemic lupus erythematosis),
causes other than AIHA must be ruled out. Though blood chemistry is often
used as a primary method for evaluation of hemolytic anemia, a specific
method for diagnosing AIHA is the direct antiglobulin test (DAT) which
identifies the presence of antibodies on the surface of the red blood cells.
Though a positive DAT is indicative of AIHA, it is important to note that
reportedly 40% of AIHA cases may yield a negative result due to clinical and
experimental variables that may effect the accuracy of the test. In
situations where the DAT is negative but there is a strong suspicion of
AIHA, a bone marrow biopsy would confirm the presence of AIHA.
What is the treatment for AIHA?
The most frequent course of
therapy for AIHA is the administration of high doses of corticosteroids such
as prednisone, which have a pronounced anti-inflammatory and
immunosupressive action that impairs functions of various components of the
immune system. Once the disease is in remission, low dose, intermittent
therapy is continued for several months. Some dogs, however, do not respond
to corticosteroid treatment and require more potent immunosuppressive drugs
that are often combined with corticosteroid treatment. Such drugs include
cytotoxic agents such as azathioprine and cyclophosphamide. Other therapies
which have been indicated in the treatment of AIHA because of their ability
to mediate immune response include Danazol, which in addition to its
immunosuppressive characteristics, is incorporated into and stabilizes the
red blood cells making them more resistant to destruction, intravenous gamma
globulin, and cyclosporine.
What is the prognosis for AIHA
The clinical course of AIHA
can range from mild and in some cases even subclinical, to severe and fatal.
Fatality is most often associated with severe and rapid red blood cell
destruction. Fatalities, however, may also occur as a result of secondary
complications. For example, breakdown of red blood cells releases coagulants
into the blood circulation that may result in pulmonary blood clots.
Additionally, fragments of destroyed red blood cells are believed to produce
kidney damage that may lead to kidney failure. Dogs experiencing
life-threatening hemolysis and requiring transfusion are at higher risk to
developing these secondary complications and therefore, are considered to
have a poor prognosis for recovery.
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The Merck Veterinary
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Recent Medical Publications on
Treatments for AIHA:
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Grundy SA, Barton C. Influence of drug treatment on survival
of dogs with immune-mediated hemolytic anemia: 88 cases
(1989-1999). J Am Vet Med Assoc 2001 Feb 15;218(4):543-6
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Zaucha JA et al. Severe canine hereditary hemolytic anemia
treated by nonmyeloablative marrow transplantation. Biol Blood Marrow
Transplant 2001;7(1):14-24
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Burgess K, Moore A, Rand W, Cotter SM. Treatment of
immune-mediated hemolytic anemia in dogs with cyclophosphamide.J Vet Intern
Med 2000 Jul;14(4):456-62
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Reagan WJ, Scott-Moncrieff C, Christian J, Snyder P, Kelly K,
Glickman L. Effects of human intravenous immunoglobulin on canine monocytes
and lymphocytes. Am J Vet Res 1998 Dec;59(12):1568-74
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Kellerman DL, Bruyette DS. Intravenous human immunoglobulin
for the treatment of immune-mediated hemolytic anemia in 13 dogs. J Vet
Intern Med 1997 Nov-Dec;11(6):327-32
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Bartges JW. Therapeutic plasmapheresis. Semin Vet Med Surg
(Small Anim) 1997 Aug;12(3):170-7
Recent Medical Publications on
Potential Causes for AIHA:
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Lobetti RG, Schoeman T. Immune-mediated haemolytic anaemia:
possible association with Ancylostoma caninum infection in
three dogs. J S Afr Vet Assoc 2001 Mar;72(1):52-4
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Skibild E et al. Haemolytic anaemia and exercise intolerance
due to phosphofructokinase deficiency in related springer
spaniels. J Small Anim Pract 2001 Jun;42(6):298-300
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McManus PM, Craig LE. Correlation between leukocytosis and
necropsy findings in dogs with immune-mediated hemolytic
anemia: 34 cases (1994-1999).J Am Vet Med Assoc 2001 Apr 15;218(8):1308-13
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Lee KW, Yamato O, Tajima M, Kuraoka M, Omae S, Maede
Y.Hematologic changes associated with the appearance of eccentrocytes after
intragastric administration of garlic extract to dogs. Am J Vet Res 2000
Nov;61(11):1446-50
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Stewart GW, Turner EJ. The hereditary stomatocytoses and
allied disorders: congenital disorders of erythrocyte membrane permeability
to Na and K. Baillieres Best Pract Res Clin Haematol 1999 Dec;12(4):707-27
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Morgan LW, McConnell J. Cobalamin deficiency associated with
erythroblastic anemia and methylmalonic aciduria in a border collie. J Am
Anim Hosp Assoc 1999 Sep-Oct;35(5):392-5
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Noble SJ, Armstrong PJ. Bee sting envenomation resulting in
secondary immune-mediated hemolytic anemia in two dogs.J Am Vet Med Assoc
1999 Apr 1;214(7):1026-7, 1021
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Birkenheuer AJ, Levy MG, Savary KC, Gager RB, Breitschwerdt
EB. Babesia gibsoni infections in dogs from North Carolina. J Am Anim Hosp
Assoc 1999 Mar-Apr;35(2):125-8
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Yamato O, Hayashi M, Yamasaki M, Maede Y. Induction of
onion-induced haemolytic anaemia in dogs with sodium n-propylthiosulphate.
Vet Rec 1998 Feb 28;142(9):216-9
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Duval D, Giger U. Vaccine-associated immune-mediated
hemolytic anemia in the dog. J Vet Intern Med 1996 Sep-Oct;10(5):290-5
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