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European Veterinary Conference

Voorjaarsdagen
Amsterdam, Netherlands
24 - 26 April, 2008

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Reprinted in IVIS with the permission of the Conference Organizers


Reprinted in IVIS with the permission of the Organizers
1 Scientific Proceedings: Companion Animals Programme
Canine Immune-mediated Hemolytic Anemia and Thrombocytopenia
Rance K. Sellon, Diplomate ACVIM (Internal Medicine), Washington State University, USA,
rsellon@vetmed.wsu.edu
Immune-mediated hemolytic anemia (IMHA) and
immune-mediated thrombocytopenia (ITP) are among
the most common hematologic disorders of dogs. IMHA
and ITP are manifestations of a type II hypersensitivity
disorder with few cases having a recognized trigger. In
some dogs, IMHA and ITP occur together. It is important
to remember that there are other causes of hemolytic
anemia (toxins, inherited erythrocyte enzyme defects,
microangiopathic disease) besides IMHA.
Clinical signs/physical examination
Most dogs with IMHA exhibit weakness or lethargy;
acute collapse is possible. Some owners notice icterus or
bilirubinuria and seek veterinary care. Owners of dogs
with ITP most commonly recognize evidence of bleeding,
although presentations that reflect anemia are also
possible. Clinical signs can develop quickly, or slowly.
Typical physical abnormalities include mucous membrane
pallor, icterus, tachycardia, heart murmurs, tachypnea
and hepatosplenomegaly. Fever is also common. Dogs
with concurrent ITP may have petechial hemorrhage, or
other evidence of bleeding.
Clinical pathology
Anemia with a normal plasma or serum protein is expec-
ted unless there has been hemorrhage; inflammatory
leukograms are common with left-shifting to the meta-
myelocyte stage in some dogs. Anemia is usually
regenerative, which is defined by reticulocytosis. Other
features that suggest, but are not specific for, regeneration
include polychromasia, anisocytosis, macrocytosis and
nucleated red blood cells; spherocytosis and autoagglu-
tination are also common. Platelets numbers in dogs
with ITP are often profoundly low (<20,000/ul), and
platelets commonly large.
Some dogs with IMHA have non-regenerative anemia.
Bone marrow aspiration cytology may show a robust
marrow response, maturation arrest or in cases of pure
red cell aplasia the marrow may lack erythroid precursors.
Some dogs will have erythrophagocytosis on bone
marrow cytology. The presence of a large number of
macrophages exhibiting erythrophagocytic activity could
reflect a malignant histiocytic disorder and hemo-
phagocytic syndrome.
Common serum biochemical abnormalities include
increased ALT and AP activity and hyperbilirubinemia,
which can be profound. Severely ill patients can have
pre-renal azotemia. Serum proteins concentrations are
136 | Abstracts European Veterinary Conference Voorjaarsdagen 2008
Internal Medicine
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usually normal although dogs that have ITP may have
hypoproteinemia from hemorrhage; dehydrated patients
may be hyperproteinemic.
Other diagnostic tests that can be used in the assessment
of IMHA/ITP patients include thoracic and abdominal
cavity imaging (to exclude neoplasia or other triggers),
testing for certain infectious diseases that can look like
IMHA/ITP (Mycoplasma haemofelis, Babesia canis,
B.gibsonii, Ehrlichia canis, Anaplasma sp.and others), and
Coomb’s testing. A negative Coomb’s test does not
exclude a diagnosis of IMHA. In dogs with non-
regenerative forms of IMHA, bone marrow cytology can
be an important diagnostic test. Normal coagulation
times (PT, PTT) help exclude consumptive causes of
thrombocytopenia. Ultimately, a diagnosis of IMHA or
ITP is based on exclusion of other causes of anemia and
thrombocytopenia.
Treatment
The principles of treating a patient with IMHA are
support of oxygen-carrying capacity, suppression of
immune responses and limiting thromboembolic com-
plications. For those patients that have a trigger identified
(e.g. infectious disease), treatment is also directed at the
primary cause.
Many, but not all, patients with IMHA require transfusion
with blood products to support oxygen-carrying capacity.
There is no “rule” for when to provide blood products
except when clinical signs dictate; for some patients,
that may mean transfusions at PCV of 20-25%, and for
others, not until the PCV is less than 12%. Packed red
blood cells are optimal for most IMHA patients since they
don’t need the protein components of plasma; if whole
blood is all that is available, it should be given.
Hemoglobin solutions (Oxyglobin®) can also support
oxygen-carrying capacity. A misperception is that blood
transfusions add “fuel to the fire” if given to an IMHA
patient. While true that transfused erythrocytes may be
destroyed by the immune system, the goal of transfusion
is to support oxygen-carrying capacity until the patient
has achieved a degree of clinical stability and improved
clinical signs. Some patients require multiple transfusions
before clinical stability is achieved.
There is no clinically proven “best” approach to immuno-
suppressive therapy, and one’s approach is typically a
reflection of approaches that have, or have not, worked
in the past. Immune suppressive therapy can also be
 Internal Medicine

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Scientific Proceedings: Companion Animals Programme 1

influenced by owner (cost tolerance) or patient (side

effects) factors. The author’s favorite approach to
immunosuppression of patients with IMHA (and often
other immune-mediated diseases) is to start prednisone
(1-2 mg/kg PO q12h) and azathioprine (1-2 mg/kg PO q24h
for 14 days, then q48h indefinitely thereafter) at the
same time, primarily to have a safety net in place if there
is a need to stop glucocorticoids sooner than preferred. If
the clients can afford it, cyclosporine (10 mg/kg PO q12-
24h) is also started with prednisone and azathioprine.
This triple therapy is considered by some as the preferred
treatment for pure red cell aplasia. The author typically
will not reduce the prednisone dose until the end of the
second or third week of treatment if response has been
prompt and a target (normal PCV) has been attained. A
20% reduction of the prednisone dose is then made with
subsequent 20% reductions made every 2-3 weeks as
long as the PCV remains stable. Patients with non-
regenerative forms of IMHA may require longer periods
of high dose therapy, and increasing reticulocyte counts
may be the first indication of successful immuno-
suppressive therapy. For patients on triple therapy, the
author typically lets the owner decide which drug-
prednisone or cyclosporine- to stop first based on
intolerance of either side effects or cost. Cyclosporine is
abruptly stopped and not tapered.
Because of the central role of the spleen in IMHA, there
has been a renewed interest in splenectomy in the
treatment of canine IMHA. However, splenectomy is still
considered by many to be a treatment of last resort.

Patients with IMHA are at risk of thromboembolic

disease. A simple and well-tolerated approach to reduce
the risk of thromboembolism is administration of aspirin
0.5 mg/kg PO q24h. The availability of platelet gpIIb/IIIa
inhibitors (e. g.clopridogrel) makes these drugs an option,
but their use in patients with IMHA has not yet been
carefully evaluated.

Abstracts European Veterinary Conference Voorjaarsdagen 2008 | 137