Sunday, July 24, 2011

Notes from July 2011 St. Louis AVMA Conference-More On Thrombolism

These are papers from the July 2011 St. Louis AVMA conference.  I’ve edited them to delete some of the vet only jargon and for space considerations.  If you see (…) that means that information has been deleted due to these considerations.  The ones listed here include HCM, and other heart related papers, treatments, papers on x-rays and echos, thrombosis, kidney disease, idiopathic cystitis, pain management, anesthesia and cardiac disease, supplements and other hazards for pets, and some other basic information I hope is helpful.

Feline Thromboembolic Disease

Meg M Sleeper VMD, DACVIM (Cardiology)

Associate Professor of Cardiology; University of Pennsylvania School of Veterinary Medicine


Arterial thromboembolism (ATE) has long been associated with cardiomyopathy.  The

syndrome is most often associated  with hypertrophic cardiomyopathy (HCM), likely because

this is the most common type of heart disease in cats.  Although a majority (89-92%) of cats

with ATE have cardiogenic emboli, neoplasia (in particular bronchogenic carcinoma), was the

cause of ATE in 5% of cats, and 3% of cats had no identifiable cause of the ATE.  In cats, most

thromboembolisms involve the left heart and systemic arteries, which causes obstruction of the

affected  artery.

History and Chief Complaint

The thromboembolic event is often the first overt sign of heart disease in a subset of

cats.  The site of cardiogenic embolization varies, but the distal aorta (“saddle embolus”) is the

most common site, representing 71% of the cases in one large study.  The right and/or left

forelegs or, less commonly, various abdominal organs can be embolized…Affected

cats can present in a variety of ways depending on the site of embolization, the duration of

occlusion, and the degree of functional collateral circulation.  Distal arterial embolization

affecting the limb(s) usually results in peracute signs of paresis, vocalization and pain.  Many

animals present with concurrent congestive heart failure (CHF) with typical clinical signs

(dyspnea, tachypnea, etc.)…

Unfortunately, most cats presenting with ATE display tachypnea because of pain,

making a definitive diagnosis of CHF impossible without thoracic radiographs.  In addition to

clinical signs associated with CHF, clinical signs secondary to the specific tissue or organ

embolized are to be expected.   Clinical signs that relate to the extremities have been

characterized by the “five Ps”: Paralysis, Pain, Pulselessness, Pallor and Poikilothermia.  The

neuromuscular ischemia secondary to vascular occlusion causes severe pain and paresis…and  the

distal limbs are cold…The nail beds and pads may appear pale to cyanotic

depending on the severity and duration of ischemia, often there is progression from pallor to

cyanosis over the first 12 hours of embolization.  Most affected cats are clinically dehydrated

and/or hypothermic…

Acute case management

Acute therapy of ATE patients is directed toward  managing pain, CHF or significant

arrhythmias when present,  general patient support, and adjunctive therapies to limit thrombus

growth or future thrombus formation.  In the acute phase, a 24-hour care facility is best suited

for these cases, as there may be acute life threatening deterioration at any time during the first

several days after ATE has occurred.  If CHF is present, therapy should be initiated similarly to

in other cats with CHF.  Analgesia is crucial in these patients, particularly for the first 24 to 48

hours, because after that time period, there is often lack of pain noted in cats with a saddle

embolus.  Analgesia can be addressed with various medications…Hypothermia is a manifestation

of poor systemic perfusion and shock rather than just local blood flow changes due to a saddle thrombus; improving  it is one of the most important goals in managing the acute crisis in ATE patients…Fluid therapy is warranted  for dehydrated patients, as long as CHF is not present, but it must be cautious in cats with significant heart disease. Vigilant monitoring of respiratory rate, effort and auscultation for the development of a gallop is particularly important

in these patients. ..Excellent supportive care in the form of good nutritional support, manual voiding of the urinary bladder, if necessary, and maintaining clean and comfortable bedding is critical in this patient population.  In some cats, a nasoesophageal feeding tube may be necessary …Self mutilation of devitalized limbs occurs in a subset of patients and is characterized by excessive licking or chewing of the toes or hock.  Application of a loose fitting

bandage barrier is usually effective.

…Sudden hyperkalemia can result from reperfusion syndrome (ischemic rhabdomyolysis and

reperfusion), which occurs when arterial blood flow is re-established to a previously ischemic

region, resulting in acute catastrophic release of potassium into the systemic circulation (9.4%

of cases in one study). Continuous recording of the ECG is one way to screen for circulating

potassium increases…In addition to the detection of hyperkalemia, the development of

reperfusion syndrome can be identified on clinical laboratory results by elevated  lactate and acidosis.  It is a life threatening condition which usually occurs hours to several days after the embolic event due to systemic release of the metabolic byproducts associated with ischemia.  Treatment should be aggressive and

immediate. Hyperkalemia can be addressed with calcium gluconate and/or insulin and glucose

to drive K+ intracellularly.  If a secondary bradycardia is present, atropine may be indicated.

Fluid therapy with sodium bicarbonate is warranted to address metabolic acidosis.

Unfortunately, the prognosis in cats which develop  reperfusion syndrome is poor, and many

cannot be rescued.

Anticoagulant  therapy has no effect on established thrombi, however by retarding

clotting factor synthesis, or accelerating  its inactivation, thrombosis  from activated bloodclotting

pathways can be prevented. The theoretical aim of anti-coagulant therapy in the acute

phase is to prevent or reduce thrombus extension. ..Although heparin has proven effective

in human trials…it has never been evaluated in spontaneously occurring feline arterial thromboembolism and reported dosages vary widely.  In spite of this limitation, heparin is part of the standard of care for hospitalized patients during the early, acute stage of ATE because of these theoretic benefits…aspirin therapy  initially has little or no effect, but eventually the effect of prostaglandin predominates…

Long term management

In retrospective studies, the proportion of affected cats with recurrence of ATE has

ranged from 24 to 75 percent and was the ultimate cause of death or euthanasia in 20 to 50

percent of the cats.  Subjectively, it appears that a large majority of cats suffering from  ATE

have recurrent  ATE, and a majority likely succumb to this disorder… it is important to keep in mind that

treating these patients can still be fulfilling  and may result in good quality of life for an extended

period of time…Therapy directed at the underlying cause of thromboembolism (most often cardiomyopathy) and CHF

(when present) is crucial for these patients…most veterinary recommendations for anti-coagulant therapy come from anecdotal experience and limited  experimental and clinical trials.  Of the available options, low dose aspirin therapy is a low risk and inexpensive option with theoretic benefit.  Clopidogrel is more costly, but also

appears to be low risk.  Antiplatelet therapies focus on the principle that exposure of blood to

subendothelial connective tissue leads to rapid platelet activation, platelet plug formation and

subsequent thrombus.  A clinical trial comparing efficacy of aspirin and clopidogrel in cats

which have experienced ATE is currently underway…the general consensus is that clopidogrel is likely more effective than aspirin for prevention of ATE…Clopidogrel is more expensive than aspirin and it should be given with food…but most cats tolerate the medication in pill pockets or gel caps.  It must be given daily, so in

cats which are particularly difficult to pill, aspirin administration every third day may be more

reasonable for the owner.  Transdermal administration of neither clopidogrel nor aspirin has

been studied and is not recommended.  Some clinicians prefer to avoid aspirin in patients with

renal disease because of possible gastric acidity; clopidogrel may be superior in these patients

as long as it does not alter their appetites…Warfarin therapy does not appear

to reduce the risk of ATE recurrence over aspirin therapy. Considering the risk of complications

to warfarin therapy and the cost of therapeutic drug monitoring, warfarin is not typically

recommended for therapy of ATE cats. For chronic therapy, UF heparin  has traditionally not been used commonly in veterinary medicine because it requires frequent parenteral administration every 6-8 hours…Moreover, whether

using UF heparin or LMWH, bleeding is a possible complication.

Prognosis and long term outcome

Although the diagnosis of cardiogenic ATE carries a poor prognosis, it is important to

keep in mind that treating these patients can still be fulfilling and may result in good quality of

life for an extended period of time. The short term prognosis depends largely on the nature and

responsiveness of the underlying  heart disease and heart failure.  Findings which suggest a

better survival rate are having a single limb rather than bilateral limb involvement and

continued motor function at presentation.  However, a number of findings suggest a more grave

prognosis including: refractory CHF or development of malignant arrhythmias, acute

hyperkalemia (secondary to reperfusion injury), clinical evidence of multiorgan or multisystemic

embolization, presence of an LA or LV clot, rising BUN/creatinine values, disseminated

intravascular coagulation, and/or unresponsive hypothermia. The owners’ commitment to

therapy and nursing care is an important factor. Notably, having a lower rectal temperature

was a significant risk factor.

References available from author

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