What
Is Auto Immune Hemolytic Anemia?
Information for Patients and Veterinarians
What is AIHA?
Autoimmune hemolytic anemia (AIHA) is a disease in which the
body attacks its own red blood cells (RBC). A pet suffering with
AIHA will have a lower-than-normal number of red blood cells
within the blood. This is termed anemia. The normal range for
the packed cell volume (PCV) or hematocrit is 37-55% (the ratio
of the volume of packed red cells to the whole blood).
AIHA is classified as a “primary” immune disease. No underlying
cause of the immune destruction can be found after an exhaustive
clinical and laboratory evaluation. A “secondary” disease is
called immune-mediated hemolytic anemia (IMHA). IMHA refers to
all anemias that occur when the immune system inadvertently destroys
its own blood cells secondary to an immune attack directed against
an underlying condition such as cancer, endocarditis, heartworm
or by unidentifiable causes as in AIHA.
What are the Symptoms of AIHA?
When a large percentage of red blood cells (RBC) are affected,
and they are removed faster then they can be replaced, the animal
shows external signs of the disease.
The clinical signs of AIHA are usually gradual and progressive,
but occasionally an apparently healthy pet suddenly collapses
in an acute hemolytic crisis. The signs are usually related to
lack of oxygen supply. The hemoglobin in RBC is the primary carrier
of oxygen in the blood. Signs include weakness, lethargy, anorexia,
and an increase in the heart rate and respiration. Heart murmurs,
pale mucous membranes (gums, eyelids, etc.), and discoloration
in the urine and/or stool may also be present. More severe cases
also have a fever and icterus (jaundice), which is a yellow discoloration
of the gums, eyes, and skin. This is due to a buildup of bilirubin,
one of the breakdown products of hemoglobin.
The diagnosis of AIHA/IMHA is usually made on these clinical
signs as well as a complete blood count (CBC). The CBC usually
shows a regenerative anemia with spherocytes. Spherocytes are
a special type of red blood cell that develops in IMHA. The blood
samples may auto-agglutinate (clump). A Coombs test may be done
to support the diagnosis.
Why My Pet?
Unfortunately no one knows why an individual pet develops AIHA/IMHA.
Certain breeds such as cocker spaniels and poodles are at a higher
risk than other breeds. Middle-aged female dogs are also at a
higher risk. However immune-mediated hemolytic anemia may occur
in any breed at anytime.
Typically, the veterinary medical field has not discovered why
an individual dog gets AIHA/IMHA. However, evidence suggests
that recent vaccinations (DHLPP) may be associated with a higher
incidence of IMHA and so has the administration of certain medications
like sulfa-trimethoprim antibiotics. Dogs with serious infections
or cancers in their body may also develop IMHA. The thought for
the underlying cause is that something (i.e., vaccine, cancer
cells) triggers the immune system to react and to create antibodies.
Accidentally the antibodies also destroy the red blood cells
and sometimes also the platelets (idiopathic thrombocytopenic
purpura); and therefore, the first sign of illness may be the
anemia.
Is There a Cure?
AIHA is better thought of as a disease that is controlled rather
than cured. Medications are used to decrease the hyperactivity
of the immune system and suppress the abnormal immune response
directed against RBC.
Treatments may need to be given indefinitely, but at least for
several months. Most dogs are on medications for at least 4-6
months, some much longer. Dogs that have had AIHA once are more
likely to get it again, particularly if they are weaned off medicines
very rapidly (less than 2 months).
What are the Treatments?
The initial drugs used are cortisone medication (prednisone,
dexamethasone). Prednisone takes approximately 5-7 days to become
effective, during which time the animal’s disease may worsen.
Other cytotoxic drugs such as imuran (azathioprine), cytoxan
(cyclophosphamide), and danazol shut down the immune cells (lymphocytes)
producing antibodies and/or stop cells of the immune system that
destroy the RBC (macrophages). Other immunosuppressive therapies
such as cyclosporine administration and a host of other experimental
treatments are or have been used by various clinicians.
Most pets with AIHA/IMHA are presented for weakness and lethargy;
i.e., the effects of anemia. The pet may require a transfusion
to improve its clinical state while immunosuppressive treatments
have time to work. The clinician may elect to give whole blood,
or more commonly packed red blood cells or synthetic hemoglobin
(Oxyglobinc).
Pulmonary thromboembolism (blood clots in the lungs) results
when abnormal clotting arises from an activation of the clotting
system due to inflammation and RBC destruction. In pets with
AIHA/IMHA, several factors, including the presence of hemolysis
(RBC destruction), IV catheters, prednisone administration, and
vascular stasis contribute to the increased clotting tendency
of the blood in dogs with IMHA/AIHA. If thromboembolism is suspected,
the pet will be given doses of heparin (100-200 iu/kg of body
weight 4x per day) and possibly oxygen to reduce the labored
breathing.
Side Effects from the Drugs
Prednisone and other cortisone medications are catabolic substances;
pets lose muscle mass and strength. Additionally, these drugs
cause increased thirst and urinations (PD/PU) by affecting kidney
concentrating ability. These drugs are potentially irritating
(ulcerogenic) to the gastrointestinal (GI) tract and can cause
vomiting with or without GI bleeding. Pancreatitis is another
potential complication associated with cortisone and aziothioprine
administration.
In some instances, the cytotoxic drugs can cause bone marrow
failure. As these drugs kill rapidly dividing cells, the development
of decreased production of white blood cells can arise and open
the pet up to life threatening infections.
When to Decrease Medications?
Typically about every 3-6 weeks, medications should be decreased
by 25-50%. Factors that are important in deciding treatment adjustments
include trends in the hematocrit and resolution of clinical signs
in the dog compared to prior examination. Cocker spaniels tend
to be weaned a little slower, and large pets may tend to be weaned
over longer time periods because of the higher level of medications
they were on. Most pets should be off medications by one year
and then be checked 3-4 times per year for the first year, and
then yearly after that.
SUMMARY
AIHA/IMHA is a life threatening immune disease that can cause
damage to vital organs through the lack of oxygen supply associated
with the resultant anemia. Owners of pets with AIHA/IMHA face
a guarded to poor prognosis for the pet at the time of diagnosis.
If an underlying disease such as cancer is discovered the prognosis
becomes complicated by the limitations associated with the underlying
cause as well.
Additionally, the destruction of RBC can result in development
of blood clotting disorders and a systemic inflammation syndrome
that looks like a severe infection clinically—the aftereffects
of these can also cause organ damage to kidneys, lungs and other
organs resulting in death or prolonged hospitalization.
This brochure was written with the wonderful help and support
from Dr. Robert Murtaugh of Dove Lewis Emergency Animal Hospital
and Dr. Elizabeth Rozanski from Tufts University School of Veterinary
Medicine. The material in this brochure was written to use as
an aide for others to learn about this terrible disease and its
effect on their pet.
Reference:
Dr. Robert J. Murtaugh, DACVIM, DACVECC is a graduate of the
University of Minnesota, College of Veterinary Medicine. Dr.
Murtaugh was formerly on the faculty at Tufts University School
of Veterinary Medicine and is currently the Director of Critical
Care at the Dove Lewis Emergency Animal Hospital in Portland,
Oregon. Dr. Murtaugh chaired the organizing committee to establish
the American College of Veterinary Emergency and Critical Care
(ACVECC). He is a past-president (1994-1996) of the Veterinary
Emergency and Critical Care Society and currently President-elect
of ACVECC.
Dr. Elizabeth Rozanski, DACVIM, DACVECC is a graduate of the
University of Illinois. She completed a residency in Emergency
and Critical Care medicine at the University of Pennsylvania
and is currently an Assistant Professor at Tufts University School
of Veterinary Medicine.
Publications:
Immune-Mediated Hemolytic Anemia and Immune-Mediated Thrombocytopenia,
Textbook of Veterinary Internal Medicine—Client Information Series,
Carol Norris, DVM, DACVIM. Copyright 2000 by W.B. Saunders Company
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