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Proceedings of the
4to Congreso ECVECCS
Emergencia y Cuidados
Críticos Veterinarios
Nov. 18-20, 2014

Salinas, Ecuador

Reprinted in IVIS with the permission of ECVECCS

Published in IVIS with the permission of ECVECCS Close window to return to IVIS

Feline Arterial Thromboembolism

John D. Bonagura, DVM, DACVIM

Veterinary Clinical Sciences, the Ohio State University

Arterial thromboembolism (ATE) is a sudden interruption of blood flow caused by a

thrombus that forms proximal to the affected site and is carried by the bloodstream to the
location of vascular obstruction. In most cases, the site of thrombus formation is an enlarged
left auricle associated with a form of cardiomyopathy. Thromboembolism has also been
associated with infective endocarditis of the aortic and mitral valves as well as left-sided,
congenital heart defects such as mitral dysplasia with valve stenosis. In terms of
noncardiogenic causes of ATE, the formation of a thrombus within the lung is another
possibility. This is usually due to pulmonary neoplasia (carcinoma), and in these cases, the
embolus might contain neoplastic cells. Presumably, a thrombus with a pulmonary venous
origin simply transits through the left side of the heart to reach the systemic arterial
circulation.
Obstruction to blood flow leads to ischemia (lack of flow to tissues) and related organ
dysfunction and tissue injury. In the absence of enough collateral blood flow, cell death or
infarction occurs in the territory supplied by the obstructed vascular bed. While localized
arterial thrombosis can occur (and is observed in dogs, horses, humans and other species),
most cases of arterial thrombosis in cats appear to originate from the left auricle and the
consequence is termed a “cardiogenic” thromboembolism.
RISK FACTORS
The main diseases associated with feline ATE are cardiomyopathy (primary and
secondary); myocarditis; infective endocarditis (comparably rare in cats); congenital heart
disease (especially mitral stenosis); and pulmonary neoplasia. More than 95% can be
explained as a cardiac originated event. Thrombi (pathological blood clots) develop when the
complicated balance between procoagulant and anticoagulant factors is altered. Three
pathophysiologic features of Virchow’s triad help to explain thrombus formation; these are 1)
blood stasis; 2) hypercoagulability; and 3) endothelial (endocardial) injury. Blood stasis is
predisposed by left atrial dilatation and loss of atrial and auricular contractility. In vitro studies
of blood in feline cardiomyopathy have suggested a possible hypercoagulable state. While
speculative, the dilatation and high pressure found within a diseased atrium and auricle
could conceivably alter the endocardial (intimal) function or even expose subendocardial
collagen, a potent attractor of platelets.
Thrombi are platelet-rich but also involve progressive incorporation of fibrin. Both anti-
platelet drugs and drugs that inhibit fibrin formation can demonstrate efficacy in the
prevention of intracardiac thrombus in humans. Only antiplatelet drugs have been studied to
a limited degree in cats as discussed below.
From a practical perspective, the echocardiographic assessment of the left atrium (LA)
and its appendage (the left auricle) represent key factors in assessing risk of ATE in cats
known to have cardiomyopathy (usually HCM). When measured from the long axis 2D image
(with no aorta in the plane), a LA of >16 mm in a mature cat is considered abnormal. Once
the LA diameter at end-systole exceeds 19 mm, the risk of ATE is considerable, and cats
should be treated with antiplatelet drugs. Similarly, if left auricular emptying velocities are

Dr. Bonagura – Feline Arterial thromboembolism Page 1

Proceedings of the Sociedad Ecuatoriana de Emergencias y Cuidados Criticos Veterinarios ECVECCS - 2014 - Salinas, Ecuador
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observed to fall below ~20 cm/sec in a cat with LA dilation, the risk of echogenic contrast
(“smoke”) is greater. Smoke represents a prothrombotic event and these cats should be
aggressively treated to prevent thrombosis. Obviously, a previously formed thrombus on the
atrial wall or a history of prior ATE in a cat indicates a high risk for recurrence. When imaging
thrombi in the left atrium, the solid, round thrombus, even if large, is a lesser concern than
the soft thrombus with a “floating” or “waving” tail. Soft thrombi pose the greatest risk for
breaking for and causing an embolization.

CLINICAL DIAGNOSIS
According to Hogan (see Current Veterinary Therapy XV), the frequency of cardiogenic
embolism in cats with heart disease has been reported to be “between 6% and 17%. Males
are overrepresented, and breeds that appear to have an increased risk are Ragdoll, Birman,
Tonkinese, and Abyssinian.”
The typical history is of a sudden loss of limb function associated with acute onset of
severe pain, especially if the thrombus goes to the typical location of the aortic trifurcation (at
the origin of the iliac arteries). At necropsy, these “saddle thrombi” are relatively large and fill
the distal aorta, external iliac arteries, and origin of the internal iliac arteries affecting blood
flow to the rear limbs and the tail. Old studies of experimental ligation of both femoral
arteries in cats (Imhoff) did NOT create the same clinical syndrome. Angiographic studies
performed in the 1960’s and 1970’s (Schwab) indicated that a lack of collateral circulation
appeared to be important to development of the clinical signs. Presumably, this is due to
vasoconstricting chemicals elaborated by the thrombus. Rarely three or even four-limb
paresis is observed. When the thrombus is massive and extends cranially to involve the
mesenteric blood supply, the cat usually exhibits excruciating pain. Clients usually recognize
loud vocalization. Due to metabolic consequences of ischemia and the fact, that many cases
are not discovered for hours, some cats are moribund with shock and metabolic acidosis at
presentation.
Some cats experience a smaller thrombotic event and do not obstruct their terminal aorta.
These thrombi these can extend to the brain leading to ischemic seizures or stroke-like
signs. Smaller single or bilateral arterial thrombi sometimes lodge in one or both rear limbs
but distal to the femoral triangle. Obstructed blood flow in the axillary or brachial artery can
lead to sudden forelimb paralysis. While spontaneous lysis of clots is the normal outcome in
cats that do not die or undergo euthanasia, a forelimb thrombus is especially likely to re-
cannulate quickly; therefore, clinical signs of paresis can be transient. Recurrent renal
thrombosis can alter renal structure and function but are usually “silent” clinically. Coronary
emboli have been observed and lead to myocardial infarction. This is one mechanism for
HCM cats to develop into a RCM phenotype.
Loss of a peripheral arterial pulse in a cat is supportive of arterial thromboembolism.
Terminal aortic embolism is generally more severe, and signs may persist for hours to
weeks, although most cats recover partial to complete limb function if given sufficient time
and care (see later). The physical diagnosis of terminal aortic embolism is straightforward
and characterized by vascular, musculoskeletal, and neurological deficits, and associated
laboratory abnormalities. The affected limbs are cool, pulseless, and pale. Occasionally the
thrombus is either partial located distal to the femoral triangle and pulses and Doppler flow
will be detected proximally. The muscles become firm to rigid due to ischemia. This is the
likely source of pain. Limb edema is not an early sign of ATE; although it may be observed
days after the event because of severe muscle injury (and predicts a poorer chance for full

Dr. Bonagura – Feline Arterial thromboembolism Page 2

Proceedings of the Sociedad Ecuatoriana de Emergencias y Cuidados Criticos Veterinarios ECVECCS - 2014 - Salinas, Ecuador
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recovery). It is probably related to inflammatory changes following rhabdomyolysis and

reperfusion injury. Lower motor neuron paresis/paralysis develops with loss of
proprioception, motor function, and eventually sensation. The sensory level moves back
down from hip to toes as reperfusion develops.
The serum creatine kinase, AST, and ALT (of apparent skeletal muscle origin) are often
elevated dramatically in ATE. The AST will be significantly higher than ALT when the
elevations are related to striated muscle damage. These enzymes also may be helpful in
recognizing ATE in a cat with severe but rapidly improving paresis of a forelimb. NT-proBNP
and cardiac troponin I are often increased due to cardiac disease. Marked increases in cTnI
should prompt consideration of myocardial ischemia/infarction.
When the diagnosis is uncertain placing a Doppler crystal over the femoral and brachial
arteries should demonstrate the loss of blood flow to the affected limbs. One can measure
and compare blood lactate or glucose in affected/unaffected limbs, but this is rarely
necessary. If a large aortic thrombus is suspected, the abdominal aorta can be imaged with
ultrasound. This is most useful if the diagnosis is in doubt or if a massive aortic embolus is
suspected. Angiography is only of historical interest.
Body temperature should be obtained as a very low temperature was associate dwith a
poor outcome in one retrospective study. The distal rectal temperature can be low due to
poor perfusion. Blood pressure should be measured in a forelimb; shock is a poor prognostic
finding. Venous blood should be drawn for chemistries, pH/lactate, and baseline clotting
times if the cat will be treated. Similarly documentation of CHF is also a poor prognostic sign.
In one retrospective study the median survival was nearly three times longer in cats without
CHF.
MANAGEMENT OF FELINE ARTERIAL THROMBOEMBOLISM
The medical management of an acute thromboembolic event demands high quality critical
and nursing care. The client should be advised about the 1) need for intensive therapy
(typically 2 to 3 days in the hospital); 2) the risk of ATE recurrence (high); 3) the need for
future daily home medical care; 4) the likely presence of underlying cardiomyopathy; 5) the
attendant costs of managing the condition; and 6) the potential for sudden death during
hospitalization (or thereafter). Understandably, these issues prompt euthanasia in many
cats, although it is stressed that at least half of cats can be released from the hospital
assuming the clients allow aggressive treatment and such therapy is delivered.
If the client decides to proceed, the first and most important treatment is analgesia with a
strong mu agonist for the first 24–48 hours following an event. While there are no
comparative studies of pain control in this condition, fentanyl is most commonly used in our
practice and provides good to excellent analgesia. Transdermal fentanyl therapy is too slow
in onset for management of this severe pain and IV administration is needed. Although
fentanyl has been administered intravenously to healthy cats at a “slow bolus dose” of
around 5 micrograms/kg, it is suggested to initiate therapy with a lower dose of 3
microgram/kg (very slow IV bolus) and follow that with an intravenous maintenance infusion
of 1 to 3 micrograms per kg per hour (not per minute). Morphine (0.1 to 0.2 mg/kg IM or SQ
q6h) or buprenorphine (0.01 mg/kg, IM or SQ, q6h) represent other options. Buprenorphine
can also provide some analgesia when administered at 0.01 to 0.02 mg/kg (10 to 20
micrograms/kg) on the buccal (oral) mucosa, and it may be useful to dispense one or two
doses to client for immediate administration should an ATE occur at home. In the absence of
hypothermia or hypotension, acepromazine (0.025 mg/kg subcutaneously) will sedate the
cat further and might alleviate vocalization. Pain in most cats is markedly diminished by 36 to

Dr. Bonagura – Feline Arterial thromboembolism Page 3

Proceedings of the Sociedad Ecuatoriana de Emergencias y Cuidados Criticos Veterinarios ECVECCS - 2014 - Salinas, Ecuador
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48 hours, allowing for less aggressive analgesia.

The current thrombotic issues can be management either actively with tissue plasminogen
activator (tPA) in an attempt to lyse the thrombus, or more conservatively by preventing
further thrombosis This is done with unfractionated heparin. Both treatments also can be
administered. No prospective studies have assessed the acute management of ATE in cats
although a multi-center trial is beginning this year.
Administration of tPA is by short-term intravenous infusion with a 1 mg/kg tPA dosage
(up to 6 mg maximal dose): 10% of the dose is given as a slow IV bolus and the rest is
infused over ~one hour. In general, tPA therapy is only offered if the cat presents within 6h
of the (witnessed) event. Tissue plasminogen activator is supplied in a 2 mg vial from
Genentech (Activase™) in the US and as a 2 or 10 mg vial from Boehringer Ingelheim
(Actilyse™) in Europe. This is expensive therapy (~$1,000), unproven (although
observational data indicate it will work in some cats), and carries the risk of bleeding and
reperfusion hyperkalemia (that can be fatal).
Heparin therapy is recommended, even if tPA is administered to prevent further
thrombosis. Standard (unfractionated) heparin consists of heterogeneous molecules with a
mean molecular weight near 15,000 Daltons. Heparin molecules bind to anti-thrombin
leading to inhibition of clotting factors (including IIa, Xa, IXa, and XIIa) and possibly exerting
a mild antiplatelet effect. Heparin therapy should be monitored with a baseline aPTT and
prothrombin time. Unfractionated heparin is administered at approximately 250 to 300
units/kg IV. Thereafter either a constant rate IV infusion or subcutaneous dosing at
approximately 150-250 U/kg subcutaneously q6 to 8h for 48–72 hours. Some clinicians will
begin clopidogrel as well (18.5 mg PO daily), but the combination of tPA, heparin, and
clopidogrel is not advised due to bleeding risk. When only heparin is given, clopidogrel can
be started.
Alternatively, low-molecular-weight heparin (LMWH) can be administered. These have a
smaller molecular weight than unfractionated heparin. These drugs are more expensive.
Both human preparations of dalteparin (FragminI® 100 IU/kg bodyweight subcutaneously
q12h) and enoxaparin (Lovenox® 1 to 1.5 mg/kg subcutaneously q12h) have been used. .
In addition to analgesia, supportive care is important. Passive warming is undertaken,
but the limbs should not be burned. As indicated above, some cats are profoundly
hypothermic, and these cats have a poorer prognosis. This finding may indicate shock
accompanied by severe metabolic acidosis. Hypotension in the absence of CHF should be
treated with fluid therapy initially; when associated with CHF dobutamine at low infusion
rates (2.5 micrograms/kg/minute) is preferred. Cats on opiates may pant in a heated, humid
environment, creating a situation that can be confused with CHF. This sign will abate once
the external environmental temperature is lowered. If true fever occurs following an ATE, IV
cefazolin or oral amoxicillin-clavalenic acid are usually effective (this can be a delayed
event). The patient should be monitored for potentially fatal hyperkalemia from potassium
leaked from necrotic muscles during the first 48 to 72 hours of treatment.
Most cats that do improve are better within 72 hours of admission and can be released
for home care. There is often asymmetry noted between the limbs. With revascularization,
tail function returns and limb function is reinstated from proximal to distal. Reassessment
every two to three days is recommended following release until the status of ischemic
tissues is determined.
Home care includes: 1) protecting the limbs; 2) daily inspection for subcutaneous or
muscle edema (a poor prognostic sign); 3) cleaning urine-soaked hair and bedding; 4)
providing a soft bed; 5) encouragement to eat; and 6) a low stress area for convalescence.

Dr. Bonagura – Feline Arterial thromboembolism Page 4

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Physical therapy of the limbs characterized by passive flexion of the limbs is encouraged.
Additional consideration should be given to a soft bandage of a contracted limb (another
adverse outcome) to place it in a functional position. If constipation becomes a problem, a
small amount of soluble fiber (1/4 teaspoon of guar gum) or some canned pumpkin may be
added to food to soften the stool.
PREVENTION OF THROMBOEMBOLISM
A number of approaches have been advocated for prevention of ATE in cats. These
include: 1) aspirin monotherapy (dosed between 5 mg to 81 mg q72h); 2) warfarin
(Coumadin® 0.5 mg PO daily); 3) low molecular weight heparins including enoxaparin
(Lovenox®, 1 mg/kg) and dalteparin (Fragmin®, 100 IU/kg) injected subcutaneously once or
twice daily; or 4) clopidogrel (Plavix®, 75 mg tablets, ¼ tablet – or 18.75 mg – PO once
daily). Retrospective reports have indicated apparently safe or well-tolerated dosages of
these drugs and effects on in vitro coagulation tests. The ongoing clinical trial evaluating
clopidogrel versus aspirin (FATCAT) has finally released preliminary data and indicates
superiority of clopidogrel over aspirin for prevention of recurrent thrombosis in cats with
HCM. There was no group receiving both treatments (these drugs work by different
mechanisms and might be complementary). Compared to aspirin clopidogrel demonstrated a
decreased rate of reoccurrence and an increased time interval between the first and second
thrombotic event (lead author: Hogan, D). In this study, median survival time increased to
approximately 14.8 months in the clopidogrel group compared to approximately 6.4
months in the aspirin group (p = 0.019; see ACVIM proceedings).
In terms of specific recommendations for cats that have never experienced a thrombotic
event, the author does not routinely prescribe antithrombotic therapy in asymptomatic cats
with a normal or minimally dilated left atrium and auricular emptying velocities >25 cm/s.
Clopidogrel (¼ of a 75 mg tablet) is prescribed for the cat with a moderate (20 mm) to
severely dilated left atrium, or when auricular emptying velocities are <20 to 25 cm/s. Adult-
regimen 81 mg aspirin dosed at one tablet PO q72h is an alternative to clopidogrel, but is
often ineffective and was less effective in FATCAT. For cats at the highest risk for ATE (LA
dilation 25 mm, echogenic smoke in LA, auricular emptying velocities <20 cm/s, or a history
of prior ATE) the author suggests more aggressive therapy with both clopidogrel (¼ of a 75
mg tablet once daily) and a very low dose daily aspirin (compounded or “crumbled” to a dose
of between 5 to 10 mg per cat daily, mixed in a gel cap; alternative: 40 to 81 mg per cat
every three days). The risk of gastric ulceration must be appreciated with these treatments
and managed if anorexia, vomiting, or anemia becomes evident; however, this has not been
a major problem. Another alternative for cats at high risk of ATE is once or twice-daily
administration of a low molecular weight heparin preparation, generally enoxaparin with
clopidogrel. There is some controversy about the efficacy of this treatment with LMWH, as
well as the best manner of monitoring LMWH therapy in cats. Clinical trials in cats with
spontaneous disease are needed to settle the issues. Practically, since these heparins are
prohibitively expensive for most clients and require one or two daily injections, the treatment
holds a low acceptability to clients. Some clinicians use low molecular weight heparin as a
bridge therapy for a few weeks following recovery of aortic ATE. Warfarin therapy is difficult
to control in cats and rarely prescribed.
PROGNOSIS
As indicated previously, experience and published retrospective reports suggest at least
50% chance for functional limb recovery if treatment is administered. Even when euthanasia

Dr. Bonagura – Feline Arterial thromboembolism Page 5

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is permitted with the first 48h, the survival rate is 39%. In a one retrospective study (Smith),
the median survival time was 223 days for cats not presenting in CHF (median survival for
those cats was 77 days). It is emphasized that there are no prospective trials of therapy.
Retrospective data probably represent less than optimal outcomes since care is not
standardized in these observational studies and many cats are euthanatized at admission.
Recurrence rates of 17% to 75% over the first year have been published, but these did not
control for preventative therapy and clopidogrel was unavailable (Laste and Harpster and
Smith and colleagues). .

Further Reading

Smith S, Tobias A, Jacob K, et al. (2003) Arterial thromboembolism in cats: acute crisis in
127 cases (1992-2001) and long-term management with low-dose aspirin in 24 cases.
Journal of Veterinary Internal Medicine 17, 73-83.

Dr. Bonagura – Feline Arterial thromboembolism Page 6

Proceedings of the Sociedad Ecuatoriana de Emergencias y Cuidados Criticos Veterinarios ECVECCS - 2014 - Salinas, Ecuador