An In-Depth Look:

CANINE IMMUNE-MEDIATED HEMOLYTIC ANEMIA

CE Article #3

Canine Immune-Mediated
Hemolytic Anemia:
Treatment and Prognosis*
Andrea Balch, DVM, MS, DACVIM
Las Vegas Veterinary Referral Center

Andrew Mackin, BVMS, DACVIM

Mississippi State University

ABSTRACT: The treatment of primary immune-mediated hemolytic anemia involves short-term

oxygen-carrying support and long-term immunosuppressive therapy.Therapeutic options include
blood transfusion, standard and more speculative immunosuppressive agents, splenectomy, and
prevention of thromboembolic disease.This article also discusses the prognosis and prognostic
indicators.

I
mmune-mediated hemolytic anemia (IMHA)
is one of the most common types of anemia
in small animals. The diagnosis of primary
(idiopathic or autoimmune) IMHA is one of
exclusion of all potential underlying causes and
identification of one or more of the following
classic signs of the disease: anemia with a
hematocrit less than 25% to 30%; evidence of
hemolysis characterized by hemoglobinemia or
hemoglobinuria; evidence of antibodies directed
against red blood cells (RBCs), with autoagglu-
tination, spherocytosis, or positive results from
a direct antiglobulin (Coombs’) test; and an
appropriate response to immunosuppressive
therapy.1–3 The pathophysiology and diagnosis
are discussed in depth in the companion article
on page 217. This article dis-
cusses the treatment and
prognosis of confirmed cases
of IMHA.
• Take CE tests
Once a diagnosis of IMHA
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has been made, aggressive
CompendiumVet.com *A companion article on pathophysiology, clinical signs, and diagnosis begins on page 217.
supportive therapy should be instituted. Most
animals with severe RBC destruction initially
require hospitalization to monitor, control, and
treat continued hemolysis. The goal of treat-
ment is stabilization of the packed cell volume
(PCV) and resolution of clinical signs of ane-
mia. Despite these apparently straightforward
recommendations, treatment success ranges
from 40% to 70% with frequent relapses.1,2,4–6
Patients rarely die from complications of ane-
mia but do die from the hypercoagulable state
and resultant disseminated intravascular coagu-
lation (DIC) or thromboembolism.1,2,4,6
SUPPORTIVE THERAPY
The average patient with IMHA presents with
severe anemia with a hematocrit less than 15% to
20%.7 In these patients, supportive care is imper-
ative to preserve normal tissue oxygenation,
acid–base homeostasis, perfusion, hydration, and
ventilation. The most important supportive ther-
apy for patients with severe anemia is mainte-

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 Canine Immune-Mediated Hemolytic Anemia: Treatment and Prognosis CE
AN IN-DEPTH LOOK
nance of proper tissue oxygenation via blood transfusion
(Figure 1). This is indicated when clinical signs such as
tachypnea, dyspnea, and tachycardia indicate the presence
of tissue hypoxia. To improve a patient’s oxygen-carrying
capacity, clinicians may administer a transfusion of
packed RBCs, whole blood, or bovine purified polymer-
ized hemoglobin solution (Oxyglobin, Biopure Corpora-
tion). Approximately 70% to 90% of patients with
IMHA require transfusion support, with a large percent-
age receiving multiple transfusions.1,2,6
The type of blood product used for transfusion
depends on product availability and patient need. Pa-
tients with hemolytic anemia are typically RBC depleted
but not volume depleted, making transfusion with
packed RBCs preferable. Hemoglobin-carrying solutions
such as Oxyglobin also improve tissue oxygenation. The
efficacy of Oxyglobin in dogs with IMHA is controver-
sial, with reports of reduced survival rates in one study8
and no detectable reduction in outcome in other stud-
ies.6,9 In general, blood is considered the ideal product for
transfusion, but Oxyglobin is warranted when blood is
unavailable or crossmatching is difficult. Patients with
concurrent thrombocytopenia and resultant blood loss
may benefit from a transfusion of fresh whole blood or
plasma as a means of replacing blood volume. However,
clinicians should remember that blood transfusion has
no significant effect on the platelet count.
In animals with hemolytic anemia, the decision to
transfuse should be based on the clinical condition of
the patient and the patient’s hematocrit. Although there
is no specific PCV that dictates whether a transfusion is
necessary, most dogs with a PCV of less than 12% to
15% need a transfusion. However, the ultimate determi-
nant of the need for transfusion should always be the
presence of anemia-related clinical signs, such as
tachypnea, tachycardia, and weakness. The blood vol-
ume to transfuse can be approximated using the follow-
ing equation:
Volume of Body
Desired change in PCV
blood for = 90 × weight ×
transfusion (kg) PCV of donated blood
This equation can be used for whole blood and packed
RBCs by simply adjusting the PCV of donated blood.
Often, the most difficult decision related to transfu-
sion is when to give the blood, but another important
issue to consider is the target PCV after therapy.
Patients with a normal regenerative response that
April 2007
231
receive a transfusion
should have a resultant
PCV of less than 25%
to 30%. In dogs, a
transfusion resulting in
a PCV of more than
30% can increase the
risk of volume over-
load, dampen the re-
generative response,
and ultimately delay
recovery.
Ideally, all animals
that require RBC prod-
ucts should be cross-
matched before a trans-
fusion. Unfortunately,
autoagglutination is
common in patients
with IMHA and can
make accurate cross- Figure 1. Patient receiving a
matching difficult or blood transfusion.
impossible because of
an inability to differ-
entiate autoagglutination from incompatible crossmatch
agglutination. Antibodies to foreign blood group anti-
gens develop approximately 5 days after an animal has
received a transfusion. Dogs that have a history of trans-
fusion and require another transfusion at least 5 days
after their first one are at increased risk for acute and
life-threatening reactions and should, therefore, never
receive a transfusion without a crossmatch. Dogs with a
history of transfusion that need an immediate transfu-
sion or cannot be crossmatched because of autoaggluti-
nation should receive blood negative for dog erythrocyte
antigen 1, universal donor blood, or bovine polymerized
hemoglobin solution. It is important to realize, however,
that transfusion reactions to the dog erythrocyte antigen
4 component of universal donor blood have been docu-
mented and pose a risk to animals that have not been
crossmatched before transfusion.10
Additional supportive therapies to consider in patients
with hemolytic anemia include fluid and oxygen thera-
pies. Intravenous fluids can help maintain adequate vol-
ume and acid–base homeostasis. Hemoglobin-related
nephropathy has not been definitively identified in dogs
but is frequently mentioned as a risk in patients with
intravascular hemolysis and can be minimized with fluid
therapy. Care should be taken to ensure that fluid ther-
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232 CE Canine Immune-Mediated Hemolytic Anemia: Treatment and Prognosis
Table 1. Relative Potency of
Corticosteroids11,a
Relative
Antiinflammatory
Drug Potency
Hydrocortisone (cortisol) 1 Cyclosporine
Prednisolone 4 Immunoglobulin
Prednisone 4
Methylprednisolone 5 or 10–25 U/kg/hr
Triamcinolone 5
Betamethasone 25
Dexamethasone 30
aIf doses are adjusted for potency, the dosing intervals remain
the same. For example, if the adjusted 0.25-mg/kg dose of
dexamethasone is administered instead of 2 mg/kg, the dosing
interval remains the same. If doses are not adjusted for potency,
the dosing intervals need to be extended.
apy does not contribute to volume overload, particularly
in patients with concurrent kidney or heart conditions.
When whole blood is used instead of packed RBCs, vol-
ume overload can be minimized by using conservative
transfusion rates or splitting the transfusion into two,
with each half given over 4 hours to slow the transfusion
rate. Oxygen therapy is of little benefit for most anemic
patients but may be helpful in animals with significant
pulmonary disease, especially those with pulmonary
thromboembolism. RBC oxygen saturation in anemic
patients is typically maximized and improves very little
with additional oxygen therapy. In severely anemic
patients, additional oxygen-carrying support via transfu-
sion is usually far more beneficial than oxygen therapy.
STANDARD IMMUNOSUPPRESSIVE
THERAPY
Numerous studies have attempted to determine the
appropriate pharmacologic therapy for the management
of IMHA. Unfortunately, the results have primarily
caused confusion. We have attempted to summarize the
results of many of these studies and list the immunosup-
pressive drugs in order of preference, understanding that
opinions may differ.
Despite the controversy, it is agreed that short- and
long-term management of IMHA involves the judicious
use of immunosuppressive agents to reduce the rate of
antibody-mediated RBC destruction.
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Table 2. Drugs Used to Treat IMHA
Drug Recommended Dosage
Prednisone 2 mg/kg PO q12–24h
Azathioprine 2 mg/kg PO q24h
10 mg/kg PO q12–24h
0.5–1.5 g/kg IV over 6–12 hr
Unfractionated heparin 250 U/kg IV or SC q6h
constant-rate infusion
Low-molecular-weight
heparin
Dalteparin 150 U/kg SC q12h
Enoxaparin 0.8 mg/kg SC q6h
Low-dose aspirin 0.5 mg/kg/day PO
Glucocorticoids
Glucocorticoids such as prednisone and dexamethasone
are the mainstay of therapy for IMHA. For many patients,
single-agent glucocorticoid therapy is the only treatment
necessary. Corticosteroids reduce the destruction of RBCs
by inhibiting phagocytosis of antibody-covered RBCs and
decreasing cytokine and immunoglobulin production. The
use of adequately immunosuppressive doses of glucocorti-
coids is imperative. Prednisone is typically dosed at 2
mg/kg PO q12–24h. Dexamethasone can also be used,
particularly in animals that cannot take oral medication.
Because dexamethasone is seven to eight times more
potent than prednisone, the dose of dexamethasone
should be reduced accordingly (Table 1).11
Unless unacceptable side effects occur, the glucocorti-
coid dose should not be reduced until the patient’s PCV
is stable and near normal reference ranges. Once remis-
sion has been maintained for 1 to 2 weeks, the glucocor-
ticoid dose can be reduced by 25% to 50% every 2 to 4
weeks.12 Treatment can generally be stopped once the
prednisone dose has been reduced to 0.25 to 0.5 mg/kg
PO q48h. Complete withdrawal of steroids should take a
minimum of 2 to 4 months.12 Patients that relapse at
decreased doses likely need to be maintained on some
degree of immunosuppressive therapy (prednisone or
another drug) for sustained periods or even, in rare cases,
for life.
Immunosuppressive doses of glucocorticoids have sig-
nificant side effects that can limit their use and frustrate
owners. Typical side effects, such as polyuria, polydipsia,
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 Canine Immune-Mediated Hemolytic Anemia CE 233
AN IN-DEPTH LOOK

polyphagia, incontinence, and panting, can be expected at initial dose rates

and are especially evident in large-breed dogs. Owners should be warned that
these side effects are expected for the first few weeks of therapy. More serious
complications include secondary infections, steroid myopathy, and gastric
ulceration, especially if the glucocorticoid is given in combination with an
NSAID.11

Other Immunosuppressive Agents

Additional immunosuppressive agents should be administered if gluco-
corticoids fail to induce remission, cause unacceptable side effects, or cannot
control the disease unless they are given at persistently high doses. Other
therapies should also be considered in patients that relapse when steroids
are tapered or stopped. Additional immunosuppressive therapy should be
included in the initial treatment protocol in patients with autoagglutinating,
intravascular, hemolytic, or nonregenerative forms of IMHA and in patients
that are transfusion dependent. Because many cases of IMHA meet one or
more of these criteria, many clinicians start all patients on early aggressive
therapy. The most common additional immunosuppressive agents used in
patients with IMHA are azathioprine and cyclosporine (Table 2). These
agents are rarely used as a substitute for glucocorticoids, especially during
initial treatment; rather, they are given in addition to standard glucocorti-
coid therapy and frequently permit more rapid reduction of steroid doses in
the event of unacceptable corticosteroid side effects.

Azathioprine
Azathioprine, a purine analogue antimetabolite that preferentially sup-
presses T-cell function, is frequently used as an additional immunosuppres-
sive agent in dogs with IMHA. Azathioprine is relatively inexpensive, and
several studies1,6,13–15 report a good response or an improved overall prognosis
in patients receiving the drug. Azathioprine is used in dogs at a dose of 2
mg/kg PO q24h. The dose is often given on alternate days when prednisone
therapy is decreased to every other day.12 Because azathioprine has a slow
onset of action (7 to 14 days), it should not be used as a sole therapy during
initial treatment, but it is ideal when used alone for long-term management.
Infrequent side effects of azathioprine therapy include anorexia, vomiting,
diarrhea, myelosuppression, hepatopathy, and pancreatitis. Complete blood
counts should be checked weekly during initial treatment because of the
myelosuppressive activity of azathioprine. In recent years, azathioprine has
become the primary additional therapy for patients with IMHA.

Cyclosporine
Cyclosporine is an immune modulator that was originally used to prevent
transplant rejection but is now used as an immunosuppressive agent for a
variety of other conditions, including perianal fistulae, granulomatous
meningoencephalitis, and inflammatory bowel disease.16–19 It inhibits T-cell
function by preventing T-cell production of the cytokine interleukin-2, a
necessary step in T-cell activation. The original vegetable oil formulation
was found to have poor and unpredictable oral bioavailability, but the cur-
rent microemulsified formulations (cyclosporine modified or microemulsi-

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234 CE Canine Immune-Mediated Hemolytic Anemia: Treatment and Prognosis
fied) have markedly improved bioavailability and attain
more consistent and predictable therapeutic blood lev-
els. Unlike cyclophosphamide and azathioprine,
cyclosporine is not myelosuppressive and is suitable for
use in patients with nonregenerative forms of IMHA.
Cyclosporine is considerably more expensive than aza-
thioprine and cyclophosphamide and requires regular
monitoring of blood levels to ensure appropriate dosing.
The recommended immunosuppressive starting dose of
oral microemulsified cyclosporine is 10 mg/kg
q12–24h.11 To reduce oral cyclosporine doses in large
dogs, ketoconazole can be added to the drug regimen.
Several studies18,20 have found that this drug combina-
tion resulted in financial savings of 40% to 70% com-
Primary IMHA requires aggressive immunosuppressive therapy, whereas
secondary IMHA is less likely to respond to immunosuppressive therapy alone.
pared with the use of cyclosporine alone. Unfortunately,
few clinical studies have reported on the efficacy of
cyclosporine in small animals with IMHA, and the use
of the drug in treating IMHA is purely anecdotal. We
have had success with cyclosporine in managing refrac-
tory IMHA, but no scientific data exist at this time to
support its use.
Intravenous Immunoglobulin
Intravenous immunoglobulin is a conglomeration of
purified and concentrated immunoglobulin derived
from human donors that has significant immunosup-
pressive effects in dogs. Intravenous human immuno-
globulin binds to macrophage Fc receptors, preventing
binding to antibody-coated RBCs and subsequent
removal from circulation. 21 Intravenous human
immunoglobulin appears to be well-tolerated and has
been associated with rapid recoveries in dogs with
IMHA with refractory and severe anemia, although
improvements in overall survival rates have not been
demonstrated. 22,23 The recommended intravenous
human immunoglobulin dosing regimen in dogs is a
single dose of 0.5 to 1.5 g/kg infused over 6 to 12
hours. 23,24 The safety of multiple infusions to treat
chronic or refractory disease has not been ascertained.
Intravenous human immunoglobulin is expensive, and
its availability is often limited, but its use has been
strongly advocated in several retrospective and labora-
tory studies.21–23,25
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Leflunomide and Mycophenolate Mofetil
Because of the significant expense of leflunomide and
mycophenolate mofetil, these immunomodulators are
generally reserved for refractory cases. Leflunomide is
an inhibitor of pyrimidine biosynthesis that has histori-
cally been used to prevent renal allograft rejection in
dogs.24 Anecdotal reports are available regarding the use
of leflunomide to treat dogs with histiocytic disease as
well as immune-mediated disorders such as IMHA, but
scientific evidence to support efficacy of the drug is
lacking. The standard recommended oral dose of
leflunomide is 4 mg/kg/day.24 Mycophenolate mofetil
inhibits an enzyme needed for purine synthesis, leading
to suppression of both B- and T-lymphocyte function.
Mycophenolate mofetil is primarily used to prevent
transplant rejection in humans but has been used to
treat other immunologic and rheumatic diseases.
Mycophenolate mofetil has been anecdotally reported to
be effective in treating a variety of immune-mediated
diseases in dogs, including myasthenia gravis.26 The rec-
ommended starting oral dose of mycophenolate mofetil
is 20 to 40 mg/kg/day divided into two or three doses.24
To date, there are no controlled studies on leflunomide
or mycophenolate mofetil efficacy in treating IMHA.
Cyclophosphamide
Cyclophosphamide is an alkylating agent with potent
myelosuppressive effects that was originally widely advo-
cated for use in patients with severe IMHA. Cyclophos-
phamide, unlike azathioprine, has not been proven to
improve clinical outcome in patients with IMHA and
has been associated with reduced survival rates in several
studies.8,13,14 The side effects associated with cyclophos-
phamide therapy include anorexia, vomiting, diarrhea,
and potent myelosuppressive effects that can lead to leu-
kopenia, neutropenia, and thrombocytopenia. Cyclo-
phosphamide can result in sterile hemorrhagic cystitis,
which previously necessitated discontinuation of therapy.
In the rare situations in which cyclophosphamide must
be used, recommendations have been made to combine
cyclophosphamide with furosemide to prevent sterile
hemorrhagic cystitis. 27 Because other immunosup-
pressive agents with less serious side effects and better
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 Canine Immune-Mediated Hemolytic Anemia CE 235
AN IN-DEPTH LOOK

efficacy are available, cyclophosphamide is no longer recommended in treat-

ing IMHA.

SPLENECTOMY
The spleen has a central role in the pathogenesis of IMHA. The spleen is
typically the major site of mononuclear phagocytic system removal of IgG-
coated RBCs in patients with IMHA and has an integral role in antigen
presentation and autoantibody production.24 Removal of the spleen can elim-
inate a major contributor to the pathogenesis of RBC destruction in patients
with IMHA but is reserved for patients that do not respond to standard
immunosuppressive therapy or that experience adverse effects associated with
drug therapy.28 A recent preliminary study29 in a relatively small group of
dogs described the use of early splenectomy to treat patients with acute
IMHA and found that dogs treated with glucocorticoids and azathioprine as
well as splenectomy within 48 hours of presentation had shorter recovery
times and higher survival rates than dogs treated with glucocorticoids and
azathioprine alone. Based on these preliminary results, further investigation
into early splenectomy is warranted, but we cannot advocate this procedure

The most common cause of death in patients

with IMHA is thromboembolism.

because of its high risk. Risks associated with splenectomy include complica-
tions associated with anesthesia and surgery and an increased predisposition
to infectious diseases (bacterial sepsis, blood-borne parasitemia) that would
normally be controlled by the spleen.

THERAPEUTIC EFFICACY STUDIES

Given the wide array of drugs and therapies that have been suggested as
possible treatments for IMHA, it can be difficult for veterinarians to deter-
mine which medications to choose when treating their patients. A number
of recent retrospective studies on relatively large groups of dogs have
attempted to address this important issue. A retrospective study13 of 70 dogs
with IMHA reported median survival times of 974 days in dogs that
received prednisone and azathioprine; 57 days in dogs that received pred-
nisone alone; 28 days in dogs that received prednisone and cyclophos-
phamide; and 15 days in dogs that received prednisone, cyclophosphamide,
and azathioprine, although there were not enough dogs in each group to
allow statistical comparison between specific treatment groups. Another ret-
rospective study8 of 88 dogs with IMHA evaluated differences in survival
rates associated with various treatments, including prednisone, dexametha-
sone, azathioprine, danazol, cyclosporine, cyclophosphamide, Oxyglobin,
and intravenous human immunoglobulin. This study did not find a signifi-
cant difference in mortality rates between animals given single and multiple
immunosuppressive drugs but did find an increased relative risk for death
associated with the use of cyclophosphamide and Oxyglobin. In addition, a
recent retrospective study6 of 151 cases reported improved survival rates in

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236 CE Canine Immune-Mediated Hemolytic Anemia: Treatment and Prognosis
dogs treated with a combination of glucocorticoids, aza-
thioprine, and ultra–low-dose aspirin compared with
dogs treated with glucocorticoids and azathioprine
alone. Despite the evaluation of relatively large treat-
ment groups, the retrospective nature of all of these
studies is a significant limitation. Retrospective studies
can be particularly affected by clinician case selection
biases in that the most critically ill patients tend to
receive treatments of last resort that attending veterinar-
ians may perceive as speculative, expensive, or overly
aggressive.
Based on anecdotal experience and the relatively lim-
ited concrete information available from current retro-
spective and prospective studies, it is reasonable to
conclude that prednisone alone or prednisone and aza-
thioprine in combination (with or without ultra–low-
dose aspirin) is the best initial treatment in most dogs
with IMHA; that cyclophosphamide is not indicated in
most patients with IMHA; and that it is uncertain
whether early splenectomy will further improve survival
The decision to administer a blood transfusion to a patient with IMHA should be based on
the presence of anemia-related clinical signs, such as tachypnea, tachycardia, and weakness.
rates. It is hoped that future prospective canine IMHA
studies involving larger case numbers will further evalu-
ate promising treatment options, such as cyclosporine,
early splenectomy, and leflunomide.
COMPLICATIONS
Dogs with IMHA that receive appropriate transfusion
support seldom die from anemia. According to several
studies, 2,4,7,15,30,31 thromboembolism, particularly pul-
monary thromboembolism, is the most common com-
plication in dogs with IMHA. Approximately 50% of
dogs with IMHA are in a hypercoagulable state at the
time of diagnosis. 2 Major factors that influence the
development of thrombus formation are described by
Virchow’s triad of vascular endothelial injury, stasis of
blood flow, and hypercoagulability, all of which can
occur in patients with IMHA. Vascular injury in dogs
with IMHA may occur secondary to the release of
inflammatory cytokines triggered by RBC destruction
and tissue hypoxia.30 Stasis of blood flow may be exacer-
bated in hospitalized patients because of cage confine-
ment and the placement of intravenous catheters. Some
veterinarians recommend avoiding the placement of
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AN IN-DEPTH LOOK
jugular catheters in patients with IMHA and the
prompt removal of all indwelling intravenous catheters
as soon as is feasible. A recent study31 confirmed the
hypercoagulable state of patients with IMHA by finding
that their platelets express 8.1-fold greater P-selectin (a
marker of platelet activation) than the platelets of
healthy patients.
The presence of all the factors associated with Virchow’s
triad predisposes patients with IMHA to thromboem-
bolism and DIC.2 DIC is a systemic thrombohemorrhagic
disorder that typically has a very poor prognosis. A provi-
sional diagnosis of DIC is based on finding abnormalities
by hematologic and hemostatic testing, including
decreased platelet concentration, prolonged prothrombin
and partial thromboplastin times, increased fibrin degra-
dation product and D-dimer concentrations, decreased fi-
brinogen concentration, and increased numbers of
schistocytes.2,32 Fourteen percent to 45% of dogs with
IMHA have evidence of DIC during treatment.1,2,15 It
may be difficult to conclusively identify true DIC in many
patients with IMHA because pulmonary thromboem-
bolism can cause many of the same clotting profile abnor-
malities reported in patients with DIC.
Current recommendations to prevent DIC and
thromboembolic disease in patients with IMHA include
the use of unfractionated heparin, low-molecular-weight
heparin, or ultra–low-dose aspirin. Standard or unfrac-
tionated heparin binds to antithrombin, causing a con-
formational change that converts antithrombin from a
slow anticoagulator to a rapid inhibitor of factors Xa
and II.16 Unfractionated heparin can be administered at
a starting dose of 250 U/kg IV or SC q6h6,33 or as a con-
stant-rate infusion of 10 to 25 U/kg/hr.34 Heparin doses
should then be titrated to prolong the partial thrombo-
plastin time to one and one-half to three times the base-
line. Unfortunately, however, unfractionated heparin has
not been shown to reduce the incidence of pulmonary
thromboembolism in dogs with IMHA. The use of low-
molecular-weight heparins such as dalteparin and
enoxaparin is becoming increasingly popular in human
medicine because of their more predictable pharmacoki-
netic properties and ability to neutralize only factor Xa.
Compared with unfractionated heparin, low-molecular-
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 Canine Immune-Mediated Hemolytic Anemia CE 237
AN IN-DEPTH LOOK

weight heparins in humans have a more predictable effect with fewer com-
plications, do not require the same extensive monitoring of clotting, and are
less likely to cause overt bleeding. Recent research35 on low-molecular-
weight heparins in dogs suggests using a starting dose of 150 U/kg SC q12h
for dalteparin and 0.8 mg/kg SC q6h for enoxaparin.36 Administration of
ultra–low-dose aspirin (0.5 mg/kg/day PO) in combination with prednisone
and azathioprine has recently been reported to improve long-term survival
in dogs with IMHA, but it was not determined whether this was due to
decreased prevalence of thromboembolic disease.6

PROGNOSIS
Unfortunately, the prognosis for dogs with IMHA is guarded. Complete
response to treatment can take weeks to months, and some patients may
require lifelong therapy. The condition can also recur despite previous or cur-
rent therapy: one recent study7 found that 15% of dogs with IMHA that sur-
vived beyond 60 days relapsed when drugs were either discontinued or tapered.
The overall mortality rate for primary canine IMHA varies in the litera-
ture from as low as 26% to as high as 70%.1,2,6,13,15 Despite this variability,

Complete response to treatment can take weeks to

months, and some patients may require lifelong therapy.

most of the literature on IMHA agrees that the number-one cause of death
is thromboembolic disease.2,6,7,30 A recent publication6 found that all necrop-
sies of patients with IMHA showed evidence of thromboembolism. The
mortality rates will undoubtedly decline dramatically once a reliable means
of preventing thromboembolic disease has been established.
Many attempts have been made to link clinical pathologic changes with
the prognosis in patients with IMHA, and although individual studies have
detected associations between specific laboratory criteria and outcomes, few
prognostic indicators are consistently reproducible in multiple studies. For
example, the mortality rate has reportedly been higher with nonregenerative
forms of IMHA16; however, this observation was not reproducible in subse-
quent clinical studies.1,5,6 Clinical pathologic abnormalities that have been
linked to increased acute or long-term mortality rates, albeit inconsistently in
all clinical studies, include persistent autoagglutination, thrombocytopenia,
leukocytosis with a left shift, hyperbilirubinemia, hypoalbuminemia, and ele-
vated serum alkaline phosphatase activities.1,4,6,8,13,15,30,37
A recent report31 that identified the presence of activated platelets in 75%
of patients with IMHA determined that quantification of platelet P-selectin
expression may be a more sensitive method than routine coagulation testing
in detecting prothrombotic tendencies in dogs with IMHA. Because
thrombosis is such a common cause of death in patients with IMHA, this
test may help identify at-risk patients, allowing earlier detection and treat-
ment and potentially improving the prognosis.
The lack of consistency in determining the prognosis for patients with

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238 CE Canine Immune-Mediated Hemolytic Anemia: Treatment and Prognosis
IMHA based on a single clinical or laboratory finding
has resulted in the recent development of a prognostic
scoring scheme. Scoring schemes are routinely used in
human medicine to predict patient outcome and com-
pare treatment protocols. A similar grading scale called
the canine hemolytic anemia objective score (CHAOS) was
recently developed to predict the survival of dogs with
hemolytic anemia and found that the median CHAOS
of the survivors was significantly lower than that of
nonsurvivors.38 This may indicate that similar scoring
protocols that account for multiple physical examination
and clinical pathologic findings may more adequately
predict the prognosis of patients with IMHA. It is
hoped that the identification of at-risk patients will
allow early intervention and improve the outcome of
this frustrating and common disease.
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2. Scott-Moncrieff JC, Treadwell NG, McCullough SM, et al: Hemostatic
abnormalities in dogs with primary immune-mediated hemolytic anemia.
JAAHA 37(3):220–227, 2001.
3. Miller SA, Hohenhaus AE, Hale AS: Case-control study of blood type,
breed, sex, and bacteremia in dogs with immune-mediated hemolytic anemia.
JAVMA 224(2):232–235, 2004.
4. Carr AP, Panciera DL, Kidd L: Prognostic factors for mortality and throm-
boembolism in canine immune-mediated hemolytic anemia: A retrospective
study of 72 cases. J Vet Intern Med 16(5):504–509, 2002.
5. Stokol T, Blue J, French T: Idiopathic pure red cell aplasia and nonregenera-
tive immune-mediated anemia in dogs: 43 cases (1988–1999). JAVMA
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AN IN-DEPTH LOOK
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April 2007
 Canine Immune-Mediated Hemolytic Anemia CE 239
AN IN-DEPTH LOOK

ARTICLE #3 CE TEST
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1. In anemic patients, ________________ does not significantly improve
oxygen-carrying capacity.
a. transfusion with Oxyglobin c. transfusion with packed RBCs
b. provision of intranasal oxygen d. transfusion with whole blood
2. On average, approximately how long after a transfusion does an animal
develop antibodies to foreign blood group antigens?
a. 1 day c. 14 days
b. 5 days d. 30 days
3. Which is not an appropriate indication for transfusion in a patient
with IMHA?
a. tachycardia c. weakness
b. tachypnea d. jaundice
4. The standard immunosuppressive dose of prednisone in dogs is
approximately _____ mg/kg/day PO.
a. 0.25 c. 2
b. 0.5 d. 6
5. Which drug is an antimetabolite that suppresses T-cell function?
a. prednisone c. cyclosporine
b. azathioprine d. danazol
6. The most common complication in patients with IMHA is
a. renal failure. c. acute hemorrhage.
b. thromboembolism. d. pulmonary edema.
7. Prevention of thromboembolism and DIC does not include admin-
istration of
a. low-molecular-weight heparin. c. aspirin.
b. an NSAID. d. heparin.
8. Intravenous immunoglobulin slows RBC destruction by
a. inhibiting pyrimidine biosynthesis.
b. inhibiting T-cell function.
c. inhibiting purine synthesis.
d. binding to Fc receptors on macrophages.
9. Administration of ____________ requires monitoring of blood levels
for adequate dosing.
a. cyclosporine c. prednisone
b. azathioprine d. cyclophosphamide
10. When unfractionated heparin is used to prevent thrombus forma-
tion, the partial thromboplastin time should be prolonged to
____________ times the baseline.
a. three to five c. five to seven
b. two-tenths to one-half d. one and one-half to three

April 2007 COMPENDIUM