TEA (Tromboembolismo)

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Feline arterial thromboembolism: an

update
Anthony Tobias
Veterinary Clinics of North America: Small Animal Practice
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Art erial T hromboembolism: Risks, realit ies and a rat ional first -line approach
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Silvia Sponhardi
T hromboembolic T herapies in Dogs and Cat s: An Evidence-Based Approach

Andrew Mackin
Vet Clin Small Anim
34 (2004) 1245–1271
Feline arterial thromboembolism: an

update
Stephanie A. Smith, DVM, MSa,*,
Anthony H. Tobias, BVSc, PhDb
a
Department of Biochemistry, College of Medicine, 506 South Mathews,
MC-714, University of Illinois, Urbana, IL 61801, USA
b
Department of Small Animal Clinical Sciences, University of Minnesota, 1365,
Gortner Avenue, St. Paul, MN 55108, USA
Arterial thromboembolism (ATE) has been recognized in cats for almost

three quarters of a century. A case report published in 1930 described the
typical clinical and necropsy findings in a cat presented for posterior
paralysis with a distal aortic thromboembolus [1]. A series of nine cases of
ATE in cats was published 25 years later [2]. By the 1960s, ATE was well
recognized, with a prevalence rate of 1 in 142 new feline admissions to the
Teaching Hospital, University of Pennsylvania [3]. The prevalence of ATE
does not seem to have changed much in the last four decades. From 1992 to
2001, ATE was diagnosed in 1 in 175 new feline admissions to the University
of Minnesota Veterinary Medical Center (UMVMC) [4].
The last seven decades have brought marked improvement in the
veterinary clinician’s ability to recognize ATE in cats and some improve-
ment in supportive measures for the acute episode but little improvement in
the prevention of ATE. Although options for anticoagulation therapy have
expanded to include a variety of new drugs, optimal thromboprophylaxis
for cats at risk for ATE has yet to be determined.
Pathophysiology
Thrombosis is the formation of a blood clot within the heart or blood
vessels. It is generally accepted that prior to development of ATE in cats, the
thrombus forms within the left side of the heart. Eventually, the thrombus
dislodges and is carried through the systemic vasculature until it becomes
lodged due to the diameter of the thrombus exceeding the diameter of the
* Corresponding author.
E-mail address: sasmith6@uiuc.edu (S.A. Smith).
0195-5616/04/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved.
doi:10.1016/j.cvsm.2004.05.006
1246 S.A. Smith, A.H. Tobias / Vet Clin Small Anim 34 (2004) 1245–1271
vessel lumen. The resulting embolus obstructs the affected artery; perhaps just
as importantly, its arrival initiates a cascade of events that lead to constriction
of collateral vessels. Interestingly, surgical ligation of the distal aorta fails to
reproduce the syndrome that is recognized clinically [5,6]. Nevertheless,
experimental induction of distal aortic thrombosis or injection of 5-hydroxy-
tryptamine (serotonin) but not saline or histamine into a surgically created
aortic cul-de-sac results in constriction of collateral vessels and an ischemic
neuromyopathy [5,7]. Administration of the serotonin antagonist cyprohep-
tadine before thrombus induction largely prevents the development of paresis
or paralysis [8]. Similarly, high-dose aspirin administered before surgical
induction of aortic thrombosis preserves collateral circulation [9]. These
findings provide indirect evidence that release of vasoactive mediators, such
as serotonin or thromboxane, from the thrombus is important in the
pathogenesis of ischemia associated with ATE [5,8–10].
The assumption that the left heart is the source of emboli is supported by
the observation that 21% of cats with hypertrophic cardiomyopathy (HCM)
have left atrial thrombi identified at necropsy [11], and intracardiac thrombi
are fairly commonly identified on echocardiography in cats with cardiac
disease [4,11–13]. The exact mechanism leading to the formation of in-
tracardiac thrombi is unclear, however. Thrombus formation may result from
alterations of the endocardial surface, blood flow, or composition of blood.
This concept, known as Virchow’s triad, provides the cornerstone for
understanding the pathophysiologic factors that predispose patients to
thrombosis. Alterations in any or all of these factors may play a role in
development of ATE in cats.
Alterations of the endocardial surface and blood flow

Disruption of the endocardial surface exposes collagen, von Willebrand’s
factor, and tissue factor, all of which may initiate thrombus formation. A
necropsy study of cats with cardiac disease described cases in which the
endocardium was damaged and cellular debris and fibrin had adhered to the
subendocardial tissues [11].
It has been postulated that atrial enlargement associated with cardiomy-
opathy leads to blood stasis and turbulence and activation of coagulation. A
recent study reported that peak blood flow velocity in the left atrial
appendage was lower in cats with cardiomyopathy (0.31 m/sec) than in
normal cats (0.46 m/sec) and even lower in cats with left atrial thrombi or
concurrent ATE (0.14 m/sec), suggesting that stasis may indeed contribute to
the formation of left atrial thrombi [14].
Most cats presented for ATE with concurrent cardiac disease have some
degree of left atrial enlargement [4,13,15]. Further, the propensity for left
atrial thrombus formation and ATE may be related to the severity of left atrial
enlargement. Specifically, it has been suggested that a left atrial dimension in
systole (LADs) greater than 2.0 cm represents a significant risk for thrombus
S.A. Smith, A.H. Tobias / Vet Clin Small Anim 34 (2004) 1245–1271 1247
formation in cats with heart disease [16]. The available data on the relative
risk for ATE as a function of left atrial size are unclear, however. In the
UMVMC study, among cats with ATE with all types of cardiac disease, the
LADs was less than 2.0 cm in just over half of the cases [4]. A study of cats with
HCM and ATE reported a LADs of 1.99 0.49 cm. Thus, consistent with the
UMVMC data, the LADs was less than 2.0 cm in approximately half of the
cats with ATE in that study [17]. The implication of these data is that heart
disease in a cat of sufficient severity to result in any left atrial enlargement
represents a risk factor for ATE. The increased risk could be caused by
alterations of the endocardial surface, blood flow, or, more likely, both.
There are also some published data to support the notion that risk for ATE
increases as a function of left atrial size. In the study of feline HCM referred to
previously, the average LADs in cats with ATE was significantly larger than
in cats with congestive heart failure (CHF) but without ATE. Further, the
average LADs was significantly larger in cats that developed ATE after the
initial examination than in cats that did not subsequently develop ATE [17].
Alterations of composition of blood

Alterations in blood composition may play a role in development of
intracardiac thrombi. A congenital or acquired coagulation protein or
platelet defect responsible for the thrombotic event is identified in more
than 50% of human patients with thrombosis [18]. Abnormalities in pro- and
anticoagulant proteins leading to hypercoagulability have not been exten-
sively investigated in cats, however. One study compared 11 cats with cardiac
disease (secondary to hyperthyroidism in nine cats) with normal cats and
reported higher antithrombin (AT) and lower plasminogen activity in those
with cardiac disease [19]. In another study, no difference was found in plasma
homocysteine concentration between normal cats, cats with cardiomyopa-
thy, and cats with cardiomyopathy and ATE. Plasma arginine and vitamin
B12 concentrations were significantly lower in cats with cardiomyopathy and
ATE, however. It is unknown whether these abnormalities were the cause of
increased thrombogenicity or occurred as a consequence of ATE [20].
Platelet hyperaggregability in cats with cardiomyopathy may play a role in
the development of ATE. In one study, platelets from cats with cardiomy-
opathy required less adenosine diphosphate (ADP) to induce aggregation
than platelets from normal cats [21]. In another study, cats with acquired
heart disease (primarily caused by hyperthyroidism) had decreased re-
sponsiveness to ADP and increased responsiveness to collagen [19].
A genetic tendency for thrombogenicity might manifest as a breed pre-
disposition for ATE. Among 195 cats in three retrospective studies, most of
the affected cats were mixed breeds. Affected pure breeds included Abyssi-
nian, Himalayan, Persian, Siamese, Manx, and Maine Coon [13,15,22]. In the
UMVMC study of 127 cats in which breed representation was compared with
the hospital population, the latter three breeds were also reported but at rates
comparable to the hospital population. Abyssinians, Birmans, and Ragdolls

were overrepresented compared with the hospital population, however [4].
This could be the result of an increased genetic risk for cardiac disease or an
unrelated genetic risk for ATE in these breeds. A single family of cats with
HCM has been described in which 75% of cats developed ATE [23]. These cats
may have all developed ATE because they had a particular form of HCM that
predisposed them to ATE. Conversely, in human beings, families with a high
density of individuals affected by thrombosis usually have an identifiable
genetic risk for thrombosis that involves coagulation protein or platelet
defects [24]. Consequently, it is possible that this family of cats could also have
carried a genetic abnormality that predisposed them to hypercoagulability.
The notion that some cats may have an inherited or acquired hyperco-
agulability is additionally supported by occasional reports of feline ATE in
which thorough diagnostic evaluations fail to identify an underlying or
predisposing disease [4]. A genetic abnormality of coagulation could explain
this apparent ‘‘idiopathic’’ thrombosis. Finally, in human beings [18] and
cats [16], a single episode of thrombosis markedly increases the risk of
developing a future thrombus, and in people, an inherited or acquired
coagulation protein or platelet defect can usually be identified.
Risk factors for development of arterial thromboembolism

Fig. 1 from the UMVMC study, shows the distribution of associated
diseases in cats presented with ATE [4]. ATE is most commonly associated
with cardiac disease, and all forms of cardiomyopathy pose a risk for ATE.
No study has reported the relative risk of ATE with specific cardiac diseases
as compared to other diseases, but ATE has been reported to occur in
12%[25], 13% [26] and 28%[17] of cats with HCM and in 41% of HCM cases
in a necropsy survey [27]. Several studies have shown that ATE is more
common in male cats than in female cats [4,13,15,22], but this is primarily
a result of the greater predisposition of male cats to develop HCM [4].
Neoplasia in cats [28], particularly pulmonary carcinoma [4,13,15], is a risk
factor for ATE, and some cats may have tumor embolism rather than
thromboembolism [4]. ATE in cats with thyroid disease has been reported in
conjunction with thyrotoxic cardiomyopathy [15]. Recently, ATE has been
reported in previously hyperthyroid cats that were euthyroid at the time of
the ATE episode and had echocardiographically normal hearts [4]. Thus,
thyroid disease seems to pose a risk for ATE that is independent of the
cardiac effects of hyperthyroidism.
Clinical presentation and initial evaluation

The clinical signs associated with ATE are referable to acute ischemia of
the tissue supplied by the occluded artery. The location of the occlusion is
dependent on the size of the embolus as well as on the anatomy of the
vascular tree. Because most thrombi that form in the atria reach a reasonably
Fig. 1. Disorders in 127 cats presenting with arterial thromboembolism (ATE) to the University
of Minnesota Veterinary Medical Center from 1992 to 2001. In 18 cats (labeled ‘‘unspecified
cardiac’’), necropsy indicated cardiac disease, but no specific diagnosis was made because
antemortem echocardiography was not performed. In 19 cats (labeled ‘‘undetermined’’), no
diagnostic tests were performed. In 3 cats (labeled ‘‘none’’), no disease was identified on
echocardiography or other diagnostic tests. The category ‘‘thyroid disease’’ includes 5 cats first
diagnosed with hyperthyroidism during evaluation for ATE and 7 cats previously diagnosed
with hyperthyroidism. DCM, dilated cardiomyopathy; HCM, hypertrophic cardiomyopathy;
HOCM, hypertrophic obstructive cardiomyopathy; UCM, unclassified cardiomyopathy. (From
Smith SA, Tobias AH, Jacob KA, Fine DM, Grumbles PL. Arterial thromboembolism in cats:
acute crisis in 127 cases (1992–2001) and long-term management with low-dose aspirin in 24
cases. J Vet Intern Med 2003;17(1):73–83; with permission.)
large size before embolizing, most thromboemboli lodge in the aorta or one
of its major branches and consequently have an impact on blood supply to
one or more of the limbs. If the embolus settles in the ‘‘saddle’’ location at the
aortic trifurcation, both rear limbs are affected. In the UMVMC study, this
was the most common presentation, occurring in 71% of cases. Smaller
emboli may travel into more distal arteries and affect arterial flow to only one
limb. Unilateral rear limb thromboembolism is much less common and may
affect either limb. Single forelimbs are occasionally affected because of
obstruction of a brachial artery, with right and left limbs affected with similar
frequency. In a few cases, forelimbs and rear limbs are both affected. Rarely,
nonappendicular sites are affected because of thromboembolism of cerebral,
renal, and mesenteric arteries [4].
Because most patients with ATE present with appendicular artery oc-
clusion, the remainder of the discussion focuses primarily on this presentation.
Occlusion of limb perfusion

Most cats with ATE are presented for acute-onset lameness, plegia, or
paralysis of the affected limbs. Affected limbs are virtually always painful,
musculature is frequently firm, and pulses are weak or nonpalpable. Nail
beds and pads may appear pale to cyanotic depending on the degree of
ischemia, and affected limbs may feel cooler than nonaffected limbs. Among
episodes of appendicular ATE in which motor function was described by the
attending clinician in the UMVMC study, some motor ability was present in
34% of cases. Forelimb and unilateral rear limb episodes were more likely to
have motor function present [4].
Manifestations of shock and pain

Most cats with ATE show signs of inadequate systemic perfusion and
shock. Shock may be maldistributive because of ischemia of the vascular bed
downstream from the occlusion and the associated release of vasoactive
substances, cardiogenic because of the underlying cardiac disease, or both.
Rectal hypothermia is common, affecting 35% [15], 65% [4], and 77% [13] of
cases. Rectal hypothermia occurs even when the distal aorta is not the
obstructed site [4] and is a manifestation of poor systemic perfusion and
shock. An additional indicator of inadequate systemic perfusion is azotemia.
Blood urea nitrogen (BUN) is increased in 41% [4], 47% [13], and 55% [15]
of ATE cases. Creatinine elevations are less common at 26% [4], 27% [13],
and 57% [15] and also tend to be less severe. An elevated BUN/creatinine
ratio may be associated with prerenal azotemia and suggests inadequate
renal perfusion. Renal artery obstruction can not be excluded as the cause of
azotemia in these cats, however.
Virtually all cats with ATE are in obvious and considerable pain as
evidenced by excitement, frenzy, vocalization, rolling, and panting. In the
UMVMC study, 89% of cats with no radiographic evidence of CHF were
tachypneic or showed open-mouth breathing [4]. Thus, in many cases,
tachypnea or open-mouth breathing is a manifestation of pain rather than
respiratory distress. This interpretation is supported by the authors’
observation that tachypnea and open-mouth breathing often subside with
analgesic therapy. The frequently observed hyperglycemia (72% [4], 85%
[22], and 93% [13]) probably results from cortisol and epinephrine release
caused by stress.
Congestive heart failure

Radiographic or necropsy evidence of CHF has been reported in 40%
[22], 44% [4], 65% [13], and 66% [15] of cats with ATE. Some cats without
evidence of CHF on presentation develop CHF while hospitalized [4]. In the
UMVMC study, cats with CHF had a slightly higher median respiratory rate
(64 beats per minute [bpm], range: 24–200 bpm) than cats without CHF (60
bpm; range: 20–160 bpm). Whereas this small difference attained statistical
significance, it is clearly not clinically relevant, and there was considerable
overlap between the CHF and non-CHF groups [4]. Thus, the presence of
concurrent CHF in cats with ATE cannot be determined from the respiratory
rate or pattern alone. Thoracic radiographs are required to determine

whether cats with ATE have concurrent CHF.
Definitive diagnosis and diagnostic approach

A diagnosis of limb ischemia is straightforward in cats that present with the
classic ‘‘five P’s’’: pulselessness, pain, pallor, paresis, and poikilothermia.
Confirming that ATE is the cause of appendicular signs can be challenging in
some cats, however. Whereas the lack of a palpable pulse is suggestive in a cat
with acute loss of limb function, it is not diagnostic for ATE. Pulse
identification is often challenging in forelimbs in cats with normal arterial
flow. Femoral pulses may also not be easy to palpate in obese or un-
cooperative cats, regardless of the level of flow. Poor-quality or absent pulses
may also be caused by systemic hypotension rather than obstructed arterial
blood flow. Additionally, partially obstructed brachial or femoral arteries
result in more subtle signs. Differential diagnoses for acute loss of limb
function should include spinal cord disease (eg, intervertebral disk disease,
spinal neoplasia, embolism, trauma, foreign body), peripheral neuropathies
(eg, diabetic neuropathy), and acute intracranial disorders (eg, embolism,
trauma, shock, neuroglycopenic crisis, toxicity).
As shown in Fig. 1, most cats with ATE have underlying cardiac disease
[4]. Consequently, the presence of a heart murmur, gallop, or arrhythmia on
auscultation lends support to a diagnosis of ATE as the cause for acute
appendicular signs. Conversely, the absence of auscultable cardiac abnor-
malities does not exclude ATE. Several retrospective studies have reported
that many cats with ATE (30% [13], 39% [15], and 43% [4]) do not have
auscultable cardiac abnormalities. Further, in most cats with ATE (76% [4],
77% [22], 89% [15]), acute appendicular signs are the first indication of
underlying cardiac disease. Because of the frequent presence of occult cardiac
disease in cats with ATE and the strong association between ATE and cardiac
disease, a thorough cardiac evaluation is appropriate for any cat in which
ATE is suspected.
Simple diagnostic evaluations may lend additional support to a diagnosis
of appendicular ATE. In cats with plegia and nonpalpable pulses, evaluation
of arterial flow by Doppler is extremely useful. ATE is probable if arterial
flow cannot be detected by Doppler. Because appendicular arteries may be
partially occluded, however, the presence of arterial blood flow does not
exclude ATE as the cause of limb paresis.
As a result of muscle ischemia, cats with ATE almost invariably have
elevations of serum enzymes released from damaged muscle cells. Increased
serum aspartate aminotransferase has been reported in 83% [13], 89% [15],
and 99% [4] of cats with ATE. Serum creatine phosphokinase, although
reported in relatively few cases, is also usually elevated (80% [22], 100% [4]),
often to a marked degree. Support for ATE may also be obtained by
comparing a venous blood sample acquired from the affected limb with that
acquired from a central vein. In one study, local venous glucose (50 25 mg/
dL) was significantly lower than central venous glucose (182 89 mg/dL) in
cats with appendicular ATE and local venous glucose was markedly lower
than central venous glucose in every case. Local venous lactate (10.7 2.7
mmol/L) was significantly higher than central venous lactate (2.1 0.8 mmol/
L) [29]. The specificity of serum muscle enzyme elevations, decreased local
glucose concentration, and increased local lactate concentration as a di-
agnostic tool to distinguish ATE from other causes of appendicular signs in
cats has not been critically evaluated. Nevertheless, the high prevalence of
muscle enzyme elevations in cats with ATE suggests that these are sensitive
discriminatory tests. Consequently, ATE is not likely to be the cause of
appendicular signs if these serum muscle enzyme concentrations are within
the reference range.
Routine coagulation tests are generally unremarkable in cats with ATE
[30]. In cats in which coagulation panels were performed before therapy,
75% were within the reference range [13]. Markers of active fibrinolysis (eg,
D-dimers, fibrin[ogen] degradation products) may be elevated [31], especially
after administration of thrombolytic therapy [13]. Serum chemistry profiles
frequently disclose electrolyte abnormalities, acidosis, and azotemia. Com-
mon electrolyte abnormalities are hypocalcemia, hyperphosphatemia, hypo-
kalemia, hyperkalemia, and hyponatremia [4].
More expensive and invasive diagnostic tests are occasionally necessary to
confirm a diagnosis of ATE. Radiography, ultrasonography, angiography,
and nuclear scintigraphy may all be used to evaluate the obstructed site
further. These imaging modalities may provide additional information,
particularly when other diagnostics have failed to identify an underlying
cause for loss of perfusion. These techniques may be useful for evaluation of
the vessel wall at the site of an obstruction, especially in cases in which the
cause of an obstruction is local rather than embolic (eg, neoplastic infiltration,
foreign body, vasculitis). Nuclear scintigraphic perfusion scans may also
provide prognostic information regarding the likelihood of recovery of limb
perfusion [32].
Management of the acute arterial thromboembolism episode

The ultimate goal of management of the acute ATE episode is to
encourage survival of the affected limb(s) and the patient. The primary
therapeutic objectives during the initial crisis are to provide rest and
analgesia, improve systemic perfusion, provide additional support, and treat
CHF if present. Resolution of limb ischemia is of secondary importance,
especially because efforts aimed at thrombus dissolution may adversely affect
patient survival [13,33]. Therapy aimed at preventing further thrombus
formation and extension is probably indicated.
Analgesia
The negative effects of pain on patient morbidity and mortality are well
documented. Clearly, analgesic therapy is essential for cats with ATE. The
particular analgesic that best addresses the pain of ATE in cats has not been
determined, and the use of a variety of analgesics, including torbutrol,
morphine, oxymorphone, and fentanyl, has been reported [4]. An extensive
discussion of analgesic therapy in cats is outside the scope of this article. For
an excellent review of analgesics for use in critically ill cats, the reader is
referred to the article by Glowaski [34].
Systemic perfusion and additional support

Improving systemic perfusion is one of the most important goals in
managing the acute crisis in ATE patients. Because these patients are often
hypothermic, application of heat sources to increase body temperature has
been advocated [35]. Hypothermia is a manifestation of poor systemic
perfusion and shock, however. External warming causes peripheral vasodi-
lation, shunts blood away from vital core organs, and, consequently, worsens
core perfusion. External warming is thus not indicated unless hypothermia
persists after systemic perfusion has been addressed.
Correcting systemic perfusion is a significant challenge in these patients,
because the precise pathophysiology of shock is seldom clear. Fluid therapy
is indicated for the dehydrated patient and those that do not have CHF.
Conversely, administering fluids to any patient with cardiac disease must be
performed with the utmost caution. Positive inotropes may have a role in
these patients, especially in cases in which depressed systolic cardiac function
has been documented echocardiographically. Nutritional support is neces-
sary in those cases that show persistent anorexia. Clearly, more research is
needed to determine the ideal approach to managing systemic perfusion and
providing additional support to cats with ATE.
Administration of acepromazine to decrease anxiety and to improve
arterial flow to the ischemic area (by its vasodilatory effect) has occasionally
been recommended [36–38]. No study has evaluated the use of this drug in
cats with ATE. Further, this hypotensive drug has the potential to exacerbate
shock. On the other hand, in the authors’ opinion, the use of acepromazine is
inappropriate for cats with ATE.
Congestive heart failure management

In cats with ATE, tachypnea does not reliably predict the presence of
CHF, and this presents a therapeutic dilemma. Many veterinary clinicians
would initially prefer to manage a cat with ATE and showing tachypnea or
another abnormal respiratory pattern with a diuretic, such as furosemide,
based on the assumption that the cat has concurrent CHF. Cats with ATE
presenting with abnormal respiratory rates and patterns should not be
treated for CHF before radiography, however, because the volume reduction
and vasodilation that result from routine CHF medications worsen systemic
perfusion. In the UMVMC study, slightly fewer than half (44%) of the cats
with ATE were suffering from concurrent CHF [4]. Consequently, thoracic
radiography should be performed before administration of furosemide to
any cat with ATE. If CHF is present, appropriate therapy is no different from
that administered to cats presenting with CHF without ATE. Cage rest,
oxygen supplementation, thoracocentesis in cats with clinically significant
pleural effusion, furosemide, and, possibly, venodilators should be used as
appropriate for the patient.
Cage rest in an oxygen-enriched environment is not detrimental to a cat
with ATE that has an abnormal respiratory rate and pattern caused by stress
and pain rather than by CHF. It is also beneficial for patients with
hypoxemia caused by pulmonary edema and pleural effusion. Consequently,
oxygen supplementation, preferably via an oxygen cage, is indicated for all
patients with ATE that present with respiratory signs.
Thrombolytic therapy
As mentioned in the introductory paragraph to this section, the authors
do not favor the use of thrombolytic therapy in the management of the acute
ATE episode. The following information is provided for completion and to
provide the basis for our opinion that the routine use of thrombolytic agents
in cats with ATE cannot be recommended based on currently available
information.
No controlled clinical trials have evaluated the use of thrombolytic agents
in cats with ATE, although several case series have been reported. A variety of
large clinical trials in human patients have compared the efficacy and safety of
tissue type plasminogen activator, streptokinase (SK), and urokinase for
treatment of coronary artery occlusion, and there are no clinically important
differences in efficacy between the three drugs [39].
Tissue type plasminogen activator

Tissue type plasminogen activator is a naturally occurring glycoprotein
that catalyzes the conversion of plasminogen to plasmin in the presence of
fibrin (Fig. 2). Human recombinant tissue type plasminogen activator is
available for clinical use. As a nonfeline protein, it has the potential to be
antigenic. The drug is supplied in a 50-mg vial, costing approximately $1100.
Information regarding the use of tissue type plasminogen activator for the
treatment of ATE in cats is limited to a single study involving six cases. In
that study, the drug was administered intravenously at a dosage of 3.0 to 8.0
mg/kg. Perfusion was restored in 64% of the affected limbs, and the rate of
survival to discharge was 50%. Reported complications were hyperkalemia,
acidosis, mild hemorrhage, and fever [40,41].
Fig. 2. The fibrinolytic pathway. For simplicity, the pathway inhibitors have been omitted.
Products of the coagulation and contact pathways initiate production of the active enzymes: two-
chain urokinase plasminogen activator (tcu-PA) and two-chain tissue plasminogen activator (tct-
PA). These enzymes cleave plasminogen to its active enzyme, plasmin. Plasmin can then cleave
additional molecules of single-chain urokinase plasminogen activator (scu-PA) and single-chain
tissue plasminogen activator (sct-PA), producing a positive feedback loop. Plasmin’s primary
action is to degrade fibrin to its degradation products. Plasmin’s activity is not exclusive to cross-
linked fibrin (x-l-fibrin). It can also degrade non–cross-linked fibrin and fibrinogen.
Consequently, the presence of elevated fibrin and fibrinogen degradation products (FDPs) is
not specific for lysis of fibrin associated with stable clots. In contrast, D-dimers are only produced
from lysis of stable cross-linked fibrin. The site of action of streptokinase (SK) is included because
of the pharmacologic use of this enzyme, but it is not a naturally occurring part of the mammalian
fibrinolytic system. FIIa, thrombin or activated factor II; FXIIIa, activated factor XIII.
Streptokinase
SK is a bacterial protein isolated from Lancefield group C strains of b-
hemolytic streptococci, a human-specific pathogen [42]. When administered
systemically, it causes thrombolysis by accelerating activation of fibrin-
bound plasminogen to plasmin (see Fig. 2) [43]. SK variants exhibit a limited
spectrum of function against mammalian plasminogens. Cleavage action is
potentially optimal for, or even restricted to, plasminogen from the species
normally infected by the bacterium that produces the SK [44]. Consequently,
SK from the human-specific pathogen may be a much less effective
thrombolytic agent in cats than in people. As a bacterial protein, it has the
potential to be antigenic. Administration to human beings has resulted in
antibody development and anaphylactic reactions [43]. The drug is supplied
in 250,000- and 750,000-U vials, costing approximately $100 per 250,000 U.
The 250,000-U vial is diluted in physiologic saline, 5 mL, and then further
diluted to 50 mL to create a 5000- U/mL solution that can be infused with

a syringe pump.
SK successfully lysed experimentally induced thrombi in normal cats. In
that study, no adverse effects during infusion were noted, but all cats were
euthanized shortly after the infusion was complete [45]. A prospective study of
thrombolysis with SK in eight cats with ATE (n = 6) and left atrial thrombi
(n = 2) evaluated a loading dose of 90,000 U administered intravenously over
30 minutes, followed by a constant rate infusion of 45,000 U/h for 3 to 6
hours. Adverse effects included neurologic signs, respiratory distress, and
electrolyte dyscrasias. All eight cats died during the constant rate infusion [6].
A retrospective study reviewed 46 cats with ATE that had been treated with
SK, most of which received a 90,000-U loading dose followed by a constant
rate infusion of 45,000 U/h for 3 to 6 hours. In 54% of cases, arterial pulses
returned, and in 30% of cases, motor function returned within 24 hours. The
rate of survival to discharge from the hospital was 33%. Reported
complications were hemorrhage (24%) and hyperkalemia (35%), with
metabolic acidosis in all cats in which acid-base status was evaluated [13].
In the UMVMC study, the rate of survival to discharge was 45% among
83 cats with ATE managed without thrombolytic therapy (all treated with
heparin and/or aspirin). Overt bleeding was not observed in any of these
patients, although 2 cats (2%) had other evidence of hemorrhage. There was
no significant difference in survival to discharge when the population of 46
cats treated with SK in the study cited previously was compared with the
UMVMC population treated without SK. Adverse effects in the SK-treated
cats were much more common, however [4,13].
In cats with ATE, ischemia of tissues distal to the thrombus is usually severe
because of the massive amount of appendicular tissue affected by the arterial
occlusion and the potential delay in presentation of cats with ATE. The
frequency of hyperkalemia, acidosis, and death suggests that reperfusion
injury is a serious problem in cats treated with thrombolytic agents. In human
beings, thrombolytic therapy is recommended in acute appendicular arterial
occlusion when associated with profound limb ischemia, except when
revascularization of the ischemic limb could jeopardize patient survival [42].
Clearly, the use of thrombolytics in cats with ATE has the potential to cause
fatal reperfusion injury. The frequency of hemorrhagic complications is also
quite high. Additionally, the use of these agents is associated with significant
cost. Given these factors as well as the lack of evidence for improved outcome
in cats treated with thrombolysis compared with cats managed without
thrombolysis, the routine use of thrombolytic drugs in cats with ATE is
difficult to justify.
Anticoagulant therapy
Anticoagulants are recommended during the acute crisis associated with
ATE. The aim of such therapy, at least in theory, is to prevent or reduce
thrombus extension and the consequent further reduction in arterial flow as

well as to reduce the risk of additional intracardiac thrombus formation.
Unfractionated heparin
Unfractionated (UF) heparin is a heterogeneous mixture of sulfated
mucopolysaccharides. It catalyzes the binding of AT and heparin cofactor II
to various coagulation factors, preventing their participation in the co-
agulation cascade (Fig. 3).
The authors recommend the use of intravenous or subcutaneous heparin
therapy during the acute phase of ATE because of the rapidity of onset of
anticoagulation but recognize that the efficacy of heparin in the treatment of
cats with ATE has not been established. In one study of cats treated with SK,
cats additionally receiving UF heparin were more likely to survive, although
the difference did not attain statistical significance [13]. Heparin is rapidly
absorbed from subcutaneous injection sites [46]. It should not be adminis-
tered intramuscularly because of the risk of injection site hemorrhage.
No outcome-based studies have evaluated any UF heparin dosage
regimen for cats with ATE, and recommendations are highly variable. In
the UMVMC study, some cats received initial intravenous therapy at doses
Fig. 3. Mechanism of action of heparin. For simplicity, only the activated forms of the
coagulation factors have been included and inhibitors other than antithrombin (AT) have been
omitted. Heparin (H) binds to AT, inducing a conformational change that allows AT to form
a stable inhibitory complex with various coagulation factors, removing them from further
participation in the coagulation cascade. Thrombin, or activated factor II (FIIa), and activated
factor X (FXa) are most significantly inhibited by unfractionated (UF) heparin. The mechanism
of action of low-molecular-weight heparin is similar to that of UF heparin, except that it is too
short to provide the necessary bridge to FIIa. FXIIa, activated factor XII; FXIa, activated
factor XI; FIXa, activated factor IX; FVIIIa, activated factor VIII; FVa, activated factor V;
FVIIa, activated factor VII; TF, tissue factor; FXIIIa, activated factor XIII.
ranging from 75 to 500 U/kg [4]. In various studies, subcutaneous UF

heparin was administered at dosages ranging from 10 to 300 U/kg every 6 to
12 hours. Most cats received either 50 to 100 U/kg (‘‘low-dose’’) or 200 to 250
U/kg (‘‘high-dose’’) every 6 to 8 hours [4,13,22].
Clinical trials in people indicate that a plasma heparin concentration
(measured by chromogenic factor Xa assay) of 0.35 to 0.70 U/mL is
associated with the greatest clinical efficacy and least hemorrhagic complica-
tions [47]. In normal cats, a UF heparin dosage of 300 U/kg administered
subcutaneously every 8 hours most consistently provides this plasma
concentration [46]. In cats with ATE, however, there is wide individual
variation in heparin pharmacokinetics, with some cats requiring much higher
dosages (up to 475 U/kg) to maintain plasma concentrations within the
therapeutic range recommended for human beings [48].
The authors’ current UF heparin dosage recommendation is 250 to 300 U/
kg administered subcutaneously every 8 hours. The first dose is administered
intravenously in cats showing signs of shock. It has been suggested that UF
heparin therapy should be monitored and titrated using activated partial
thromboplastin time (aPTT) or activated clot time (ACT). The recommen-
ded target is a 1.5- to 2.5-fold aPTT prolongation when compared with
normal plasma control or prolongation of the ACT by 15 to 20 seconds
[47,49]. These target aPTT and ACT prolongations with heparin therapy
should, at best, be regarded as rough guidelines. There are wide variations in
the sensitivity of aPTT reagents and in individual patient aPTT response to
a given heparin concentration, which results in inconsistencies in degree of
anticoagulation measured with this approach. The ACT is even less
predictive of plasma heparin concentration [46,48,49]. Further, in one report
of cats with ATE, a 1.5- to 2.5-fold prolongation in aPTT occurred at plasma
concentrations in most cases below the recommended therapeutic range for
human beings [48]. Consequently, the authors do not routinely monitor
aPTT or ACT in cats being treated with UF heparin. Plasma heparin
concentration measured by chromogenic factor Xa assay would be a more
accurate method to titrate the heparin dose, but the test is not widely
available at present. Additional information about the chromogenic factor
Xa assay is provided below.
Low molecular weight heparin

Small heparin polysaccharides are unable to bind thrombin (activated
factor II [FIIa]) and AT simultaneously. Consequently, low molecular weight
(LMW) heparin is unable to catalyze the inactivation of thrombin by AT but
retains the ability to enhance the inhibition of activated factor X (FXa) and
other coagulation factors by AT (see Fig. 3). In human beings, for equivalent
antithrombotic effect, LMW heparin is associated with less bleeding than UF
heparin and also requires less frequent administration [47]. Because frequency
of administration is not generally an issue in hospitalized patients, LMW
heparin offers no practical advantage over UF heparin for short-term
anticoagulation in cats with ATE. The reader is referred to the section on

long-term management for more information on LMW heparin.
Aspirin
Aspirin (acetylsalicylic acid) is a cyclooxygenase inhibitor that irreversibly
inhibits the production of thromboxane A2 (TXA2) in platelets. Because
TXA2 is a potent platelet aggregator and vasoconstrictor, aspirin decreases
platelet aggregability and vasoconstriction in response to injury. Aspirin
administered during or immediately after acute myocardial infarction is
associated with improved outcomes in people [50]. The pathogenesis of the
obstruction is different, however, because human coronary arteries are
occluded by thrombi that form locally at the site on an atherosclerotic
plaque, whereas cats with ATE present with thrombi that have embolized
from the heart to an arterial site. No controlled trials have evaluated the
efficacy of aspirin for acute management of ATE in cats, but in an
experimental model, cats given aspirin, 650 mg, administered orally 1 hour
before thrombus occlusion of the aorta had better collateral circulation than
non–aspirin-treated controls [51]. The authors usually initiate aspirin
therapy as soon as oral drug administration becomes possible, and preferably
once the cat has begun eating so as to minimize gastrointestinal irritation.
Further information about the dose and frequency of administration of
aspirin is provided below. Heparin therapy is discontinued 2 to 3 days after
the patient is stable and receiving aspirin.
Short-term outcome
Arterial thromboembolism in cats virtually always occurs as a devastating
complication of significant underlying disease. It usually results in severe
hemodynamic compromise that is difficult to manage as well as severe serum
electrolyte and acid-base abnormalities. Arterial thromboembolism is thus
inevitably associated with a poor prognosis. Reported rates of survival to
discharge are 33% [13], 35% [4], 37% [15], and 39% [22]. Euthanasia is
common at 24% [4], 29% [22], and 35% [15].
Most reports do not distinguish between euthanasia with no attempt to
treat versus euthanasia as a result of deterioration or lack of response to
treatment. Clearly, this is an important distinction because it introduces the
influence of clinician bias and owner commitment in the face of a disease with
a poor prognosis. In the UMVMC study, survival to discharge was 45%
when cats that were euthanized with no attempt to treat were excluded from
the analysis [4]. Further, survival in that study gradually improved over the
10 years reviewed, with 73% of cats treated for acute appendicular ATE in
the year 2001 surviving to discharge.
Significant differences between survivors and nonsurvivors have been
reported for rectal temperature [4,13] and heart rate [4], with both being
higher among survivors. Having only one limb affected [4,15] and the presence
of motor function [4] were significantly more frequent among survivors.

Serum phosphorus concentration was slightly but significantly higher among
nonsurvivors [4]. Data from the 127 cats with acute ATE that comprised the
UMVMC retrospective study were used to develop a logistic regression model
to predict the probability of survival to discharge. Once rectal temperature
was included in the model, no other variable improved the accuracy of
prediction. The model, presented in Fig. 4, predicts a 50% probability of
survival at a rectal temperature on admission of 98.9(F. It correctly classified
67% of survivors and 79% of nonsurvivors in the UMVMC study [4]. Rectal
temperature is easily measured and provides important prognostic informa-
tion. Its prognostic value probably stems from the fact that a low rectal
temperature, as well as other variables (eg, azotemia), reflects compromised
overall hemodynamic status.
Long-term management
Underlying disease
Because most cats with ATE have underlying cardiac disease, appropriate
therapy for manifestations of the cardiac disease is necessary. Similarly,
therapy for cats with neoplasia and any other concurrent and underlying
Fig. 4. Logistic regression model predicting survival probability to discharge based on rectal
temperature at admission. The equation for the predictive model is:
1
P¼
1þ e47:58593þ0:4811605 T
where P is survival probability and T is rectal temperature. (From Smith SA, Tobias AH, Jacob
KA, Fine DM, Grumbles PL. Arterial thromboembolism in cats: acute crisis in 127 cases (1992–
2001) and long-term management with low-dose aspirin in 24 cases. J Vet Intern Med
2003;17(1):73–83; with permission.)
diseases should be provided. A discussion of these therapies is beyond the

scope of this article, however.
Thromboprophylaxis
Aspirin
Thromboprophylaxis with aspirin is commonly recommended for cats at
risk for ATE at a dose of 81 mg per cat administered orally every 48 to 72
hours [35,52]. Aspirin has been prescribed at this dose for decades, but
clinical evidence suggests that its efficacy for preventing ATE is questionable
[15,25,52]. In human beings, a low aspirin dosage (1 mg/kg every 24 hours)
effectively prevents recurrent thrombosis in a variety of disorders [53]. This
low dose may be effective, in part, because it is sufficient to inhibit platelet
cyclooxygenase irreversibly (thereby limiting platelet aggregation) although
it spares endothelial prostaglandin I2 synthesis. Endothelial prostaglandin I2
is a vasodilator, and it inhibits platelet aggregation outside the area of injury,
thereby limiting thrombus growth. It remains to be determined whether or
not a lower dosage of aspirin benefits cats at risk for ATE. Nevertheless,
a recent report of long-term therapy in 24 cats with previous ATE showed
that aspirin at a dose of 5 mg per cat administered every 72 hours
was associated with similar or lower rates of ATE recurrence when com-
pared with other thromboprophylactic therapies, and adverse effects were
minimal [4].
The use of aspirin requires no specific monitoring but it has the potential
to cause gastrointestinal side effects, including anorexia, nausea, vomiting,
hematemesis, and ulceration at any dosage. Aspirin has the distinct
advantages of being inexpensive and orally administered. It is readily
available, although the low aspirin dose requires compounding.
Warfarin
The vitamin K–dependent coagulation proteins (II, VII, IX, and X) and
regulatory proteins (protein C and protein S) are synthesized as inactive
prozymogens. These prozymogens are converted to their active forms by the
enzyme vitamin K epoxide reductase. Warfarin exerts its anticoagulant effect
by inhibiting this enzyme [54].
Anecdotal reports of the use of warfarin in cats at risk for ATE suggest
a starting dose of 0.5 mg per cat per day [16]. The pharmacokinetics and
pharmacodynamics of warfarin in normal cats indicate an appropriate initial
dose of 0.06 to 0.09 mg/kg/d, although there is marked individual variation
and the drug has a narrow therapeutic index [54,55]. The pharmacodynamics
in sick cats at risk for ATE have not been evaluated. Warfarin is highly
protein bound (primarily to albumin) in cats [54], and minor shifts in
albumin status or concomitant use of other protein-bound drugs may result
in massive changes in the degree of anticoagulation.
Warfarin (Coumadin) is supplied as a 1-mg tablet, but the drug is

unequally distributed within the tablet. Tablets should not be broken for
administration but crushed and mixed well [54]. The powder can be weighed
out by a compounding pharmacist and used to fill gelatin capsules.
Prothrombin time (PT) is the laboratory test recommended for monitor-
ing warfarin therapy, and it must be adjusted for variations in thrombo-
plastin reagent and laboratory technique. The laboratory should provide
a method-specific index of responsiveness of the thromboplastin reagent,
called an international sensitivity index (ISI). An international normaliza-
tion ratio (INR) is then calculated as follows: INR = (Patient PT/Control
PT)ISI.
In human beings, the recommended therapeutic range for the INR
depends on the condition predisposing to thrombosis. No studies have
prospectively evaluated the effectiveness of any warfarin regimen in animals.
In cats, an INR of 2.0 to 3.0 is generally recommended [16], because this level
of anticoagulation is associated with minimal hemorrhage and reasonable
efficacy in people. Limited experience with the use of warfarin in cats suggests
that although an INR of 2.0 to 3.0 is an ideal goal, a wider INR range may
have to be acceptable to the veterinary clinician. Further, although
monitoring warfarin by means of the INR is well established in human
beings, its validity in feline medicine has not been critically evaluated.
Because the ISI is determined using samples from human beings, this measure
of thromboplastin response may not apply to cats.
Warfarin should only be administered once anticoagulation has been
achieved with heparin, because hypercoagulability may develop when
warfarin therapy is initiated as a result of decreased protein C and protein
S levels [16]. Warfarin and heparin therapy should overlap for at least 4 to 5
days. No validated recommendations for monitoring warfarin therapy in
cats are available, but anticoagulation monitoring should be performed
frequently, especially when warfarin therapy is initiated. When warfarin
therapy is initiated in human patients, an INR is determined daily while the
warfarin dose is being titrated until the INR is in the therapeutic range for 2
consecutive days. The testing intervals are then gradually extended to weekly
and then to monthly in those patients on long-term therapy in whom test
results have been stable [16]. The timing of blood sample collection in
relation to the administration of the drug is unimportant, because the PT is
dependent on coagulation factor concentrations at the time of sampling
rather than on plasma warfarin concentration. Anticoagulation status
should be re-evaluated with any change in concurrent drug therapy, because
many drugs affect warfarin-protein binding.
Potential adverse effects of warfarin include hemorrhage, which may be
severe and possibly fatal, skin necrosis (not reported to date in cats), and
teratogenicity. Warfarin is relatively inexpensive, but the costs associated
with its use in cats are much higher than aspirin because of the requirement
for drug reformulation and frequent INR monitoring.
Heparin
Because UF heparin requires frequent parenteral administration to
achieve consistent anticoagulation, it is generally not suitable for long-term
therapy. In human beings, LMW heparin requires less frequent parenteral
administration, but there is little published information about the use of
LMW heparin in cats. A small study of dalteparin (Fragmin) in normal cats
given at a rate of 100 or 200 U/kg every 24 hours for 5 days showed that the
lower dosage resulted in plasma heparin concentrations in the therapeutic
range. This conclusion was based on chromogenic factor Xa assays
performed on plasma collected 4 hours after the fifth injection. In one cat
in which the plasma heparin concentration was measured at 2, 8, 12, and 24
hours after injection, the concentration fell below the therapeutic range by 8
hours [56]. A separate study of the pharmacokinetics of enoxaparin (Love-
nox) in normal cats suggested an initial dose of 100 U/kg administered
subcutaneously every 24 hours (D.L. Kellerman, DVM, Manhattan, KS,
personal communication, 1997). One of the authors has attempted long-term
therapy with enoxaparin starting at 100 U/kg administered subcutaneously
every 24 hours in three clinical feline patients. Chromogenic factor Xa assays
disclosed that the dosage was appropriate but that the administration
interval was not. Two cats required enoxaparin administration every 12
hours, and one required administration every 8 hours to maintain plasma
heparin concentrations within the therapeutic range (S.A. Smith, DVM, MS,
unpublished data). Thus, although there is little information available on the
use of LMW heparin in cats, current evidence suggests that dalteparin and
enoxaparin require more frequent parenteral administration than every 24
hours. Further, the pharmacokinetics may be variable in cats at risk for ATE,
as has been recognized for UF heparin [48].
Because LMW heparin does not bind to thrombin, it has little impact
on the aPTT. Consequently, the chromogenic factor Xa assay is required
to measure plasma heparin concentrations when LMW heparin is used.
This assay is available commercially through the Cornell University
Coagulation Laboratory. Submission information may be obtained at:
http://web.vet.cornell.edu/public/coaglab/heparin.htm. Based on studies
in human beings and experimental animals as well as on personal
experience with several cats (S.A. Smith, DVM, MS, unpublished data),
it seems that once an appropriate dosage regimen has been determined for
an individual, the plasma heparin concentration remains fairly constant
over time.
Potential adverse effects of heparin therapy include hemorrhage,
thrombocytopenia (not reported in cats to date), and osteoporosis (seen
in one case treated with UF heparin for 18 months by one of the authors).
In human beings, all the adverse effects seem to be less frequent with LMW
heparin [47]. UF heparin is relatively inexpensive. Markedly higher costs
associated with the use of LMW heparin may limit its use in veterinary
patients.
Other platelet antagonists

Ticlopidine and clopidogrel are thienopyridine derivatives. Ticlopidine
has no direct platelet effects, but extensive hepatic biotransformation results
in active metabolites in human beings. Clopidogrel and the active metabolite
of ticlopidine irreversibly antagonize ADP receptors on platelet membranes,
interfering with primary and secondary platelet aggregation. Ticlopidine at
dosages of up to 100 mg per cat per day failed to alter feline platelet function,
possibly because of lack of hepatic biotransformation to the active
metabolite [57]. Clopidogrel administered orally to normal cats at 18.75 to
75 mg per cat per day significantly decreased in vitro platelet aggregation in
response to ADP and collagen and significantly increased oral mucosal
bleeding time. The maximal effect was reached within 3 days of initiating the
drug and resolved within 7 days of discontinuing the drug. No adverse effects
were noted [58]. The use of clopidogrel for thromboprophylaxis in cats at risk
for ATE has not been reported.
Eptifibatide is a glycoprotein IIb/IIIa receptor antagonist that inhibits
feline platelet aggregation in vitro [59]. At doses required to maintain platelet
inhibition in normal cats, however, the drug was associated with idiosyn-
cratic and unpredictable circulatory failure and sudden death. Use of
eptifibatide is consequently not recommended in cats [60]. A drug with
a similar mechanism of action, abciximab, was evaluated in a model of
arterial injury in cats. Cats received aspirin alone or aspirin and abciximab.
Cats in the aspirin and abciximab group showed significantly greater
inhibition of platelet function and less thrombus formation than those
receiving aspirin alone [61].
Choosing an anticoagulant
No prospective studies have been conducted to determine the safest and
most effective anticoagulant for thromboprophylaxis in cats. Table 1
summarizes some of the results from several retrospective studies of ATE in
cats in which a variety of anticoagulants were prescribed. A few cases (n = 5)
are included from one study that reported long-term survival, without ATE
recurrence in some cases, despite the lack of any anticoagulation [22]. The case
numbers reported in these studies are small, making interpretation of the
survival data difficult. Inclusion criteria vary between studies, and survival
times are thus not readily comparable. Nevertheless, it is apparent that the
currently available survival data do not clearly support the use of a particular
anticoagulant over any of the others. Consequently, the choice of anticoag-
ulant for thromboprophylaxis in cats must be based on factors other than
survival, such as ease of administration and monitoring, incidence of adverse
side effects, and cost.
Given the lack of a demonstrable survival benefit, the need for repeated
examinations, the cost of anticoagulation monitoring, and the risk of fatal
hemorrhage, the use of warfarin in cats at risk for ATE is difficult to justify.
UF and LMW heparin both require parenteral administration at least once
Table 1
Results of several thromboprophylactic protocols prescribed in various studies of arterial thromboembolism in cats
If
Recurrence recurrence, Adverse
S.A. Smith, A.H. Tobias / Vet Clin Small Anim 34 (2004) 1245–1271
Drug n MST rate (%) % fatal effects Reference Notes
Standard-dose 8 61 NR NR NR [25] Population composed of cats with
aspirina hypertrophic cardiomyopathy that
survived [24 hours after presentation
18 149c,d 28 83 22% [4] Population composed of cats that
gastrointestinal signs survived to discharge from the hospital
10 184 30 67 NR [22] Includes 3 cats that died \7 days
after presentation
Low-dose 24 105c,d 25 40 4% [4] Population composed of cats that survived
aspirinb gastrointestinal signs to discharge from the hospital
Warfarin 12 51d 45 NR 17% [13] Population composed of cats that survived
fatal hemorrhage to discharge from the hospital; all cases
initially treated with streptokinase
17 69e 24 100 18% hemorrhage [62]
f
18 44 63 11% fatal hemorrhage [15]
Dalteparin 14 255e 43 24 NR [62]
None 5 450 40 50 [22]
Abbreviations: MST, median survival time; n = number of cases; NR, not reported.
a
Standard dose was 81 mg per cat administered every 2 to 3 days.
b
Low dose was 5 mg per cat administered every 3 days.
c
Not different when survival curves were compared by log-rank test.
d
Not different when survival curves for standard-dose aspirin and low-dose aspirin were combined and compared by log-rank test with survival curve for
warfarin.
e
Not different when survival curves were compared by log-rank test.
f
The population only included those cases for which follow-up information was available. Cases that were lost to follow-up were excluded rather than
1265
censored. Consequently, MST is not reported, because survival analysis could not be performed correctly.
a day, and usually more frequently than that. Further, the cost of LMW
heparin is likely to limit its use for long-term thromboprophylaxis in cats.
Among the various platelet antagonists, aspirin is associated with gastroin-
testinal side effects, but this is more common at a dose of 81 mg per cat
administered every 48 to 72 hours than at the low dose of 5 mg per cat
administered every 72 hours. Further, low-dose aspirin is inexpensive and
requires no monitoring. At present, other platelet antagonists are too
investigational to recommend for routine use. Consequently, the authors’
current preference for thromboprophylaxis in cats is aspirin at a dose of 5 mg
per cat administered every 72 hours. The authors also recognize that it
remains to be established whether low-dose aspirin or any other anticoag-
ulant provides a significant morbidity and mortality benefit over not
prescribing thromboprophylaxis at all in cats at risk for ATE.
Long-term prognosis
Return of limb function
Affected limbs have the potential for complete return of function.
Nevertheless, neurologic function may not return, tendon contracture may
occur, or ischemia may result in tissue necrosis, necessitating wound
management, skin grafting, or amputation. Fortunately, permanent limb
damage is the exception rather than the rule, although time to complete
recovery may be days, weeks, or even months [22]. In the UMVMC study,
among 44 cats that were discharged after recovering from their acute ATE
episode, 2 (5%) developed limb necrosis requiring that the limb be amputated,
2 (5%) had minor tissue necrosis requiring wound management, and 1 (2%)
developed limb contracture [4].
Recurrence of arterial thromboembolism

Table 1 lists the recurrence rates of ATE in cats treated with a variety of
anticoagulants. Recurrent ATE occurred in 24% to 45% of cats in the
various studies, with some cats experiencing multiple episodes. Recurrent
episodes are often fatal or prompt euthanasia [4,13,15,22,25,62].
Survival predictions
In the UMVMC study, the presence or absence of concurrent CHF during
an acute ATE episode had no significant effect on survival to discharge. The
presence of concurrent CHF did have a significant deleterious effect on long-
term survival after discharge, however. Cats with CHF during the initial
ATE episode had a median survival time of 77 days, whereas cats without
concurrent CHF had a median survival time of 223 days. No cat with CHF
and ATE survived longer than 254 days. These findings suggest that most
cats with ATE have a poor long-term prognosis primarily because they are
Box 1. Recommendations for cats presented acutely with

arterial thromboembolism
Physical examination, including rectal temperature for
prognostic information
Emergency management
Placement in oxygen-enriched environment if respiratory rate
or pattern is abnormal
Administration of analgesic therapy (eg, morphine,
oxymorphone, torbutrol, fentanyl)
Initial diagnostics
Thoracic radiographs to determine if pulmonary edema or
pleural effusion is present
Serum chemistry to assess electrolyte status and check for
azotemia
Urine specific gravity before any furosemide or fluid therapy
Follow-up diagnostics
Complete cardiac workup, including echocardiography and
electrocardiography
Thyroid status if age appropriate
If no evidence of cardiac disease, additional diagnostics to
assess for occult neoplasia
In-hospital short-term management
Congestive heart failure management if indicated by results of
thoracic radiographs
Heparin (unfractionated), 250 to 300 U/kg, administered
subcutaneously every 8 hours (first dose administered
intravenously if evidence of shock). Because of the lack of
predictive value of the activated clot time or activated partial
thromboplastin time, we do not routinely monitor heparin
therapy at the University of Minnesota Veterinary Medical
Center. Ideally, the chromogenic activated factor X assay
should be performed.
Intravenous fluid therapy if clinically indicated and patient not
in congestive heart failure
Nutritional support (generally by nasoesophageal tube
feeding) if clinically indicated
Long-term management
Aspirin, 5 mg per cat, administered orally every 3 days initiated
as soon as the patient is eating.
Discontinue heparin gradually over 2 to 3 days after patient is
stable and receiving aspirin
suffering from serious and frequently advanced underlying (usually cardiac)

disease rather than specifically because of the difficulty in preventing
recurrent ATE. This is further illustrated by the fact that recurrent ATE
was the ultimate cause of death or euthanasia in only 20% of the cats in the
UMVMC study. Progressive CHF is a much more common cause for death
or euthanasia among cats that were discharged after recovering from an
acute episode of ATE [4,22]. Nevertheless, recurrence of ATE remains
a significant and frequently devastating problem. Further research is
necessary to establish a safe, effective, and practical method for thrombo-
prophylaxis in at-risk cats.
Summary
ATE remains a devastating complication of cardiac disease. Despite some
improvements in our understanding of the underlying causes and clinical
features of this disease, short-term management remains a challenge, and
mortality is high. Long-term mortality is primarily attributable to the severe
underlying cardiac disease. Many questions remain to be answered regarding
the ideal management approach for feline ATE. The authors’ preferred
diagnostic and therapeutic approaches for these difficult patients are detailed
in Box 1.
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Tradução Técnica - Inglês (opção 14) (1)

T hromboembolic T herapies in Dogs and Cat s: An Evidence-Based Approach

Feline arterial thromboembolism: an

Arterial thromboembolism (ATE) has been recognized in cats for almost

Alterations of the endocardial surface and blood flow

Alterations of composition of blood

comparable to the hospital population. Abyssinians, Birmans, and Ragdolls

Risk factors for development of arterial thromboembolism

Clinical presentation and initial evaluation

Occlusion of limb perfusion

Manifestations of shock and pain

Congestive heart failure

rate or pattern alone. Thoracic radiographs are required to determine

Definitive diagnosis and diagnostic approach

Management of the acute arterial thromboembolism episode

Systemic perfusion and additional support

Congestive heart failure management

Tissue type plasminogen activator

diluted to 50 mL to create a 5000- U/mL solution that can be infused with

thrombus extension and the consequent further reduction in arterial ﬂow as

ranging from 75 to 500 U/kg [4]. In various studies, subcutaneous UF

Low molecular weight heparin

anticoagulation in cats with ATE. The reader is referred to the section on

of motor function [4] were signiﬁcantly more frequent among survivors.

diseases should be provided. A discussion of these therapies is beyond the

Warfarin (Coumadin) is supplied as a 1-mg tablet, but the drug is

Other platelet antagonists

Recurrence of arterial thromboembolism

Box 1. Recommendations for cats presented acutely with

suﬀering from serious and frequently advanced underlying (usually cardiac)

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