Notes from July 2011 St. Louis AVMA Conference-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.

MANAGING FELINE THROMBOEMBOLISM

Philip R Fox, DVM, Dipl ACVIM, ECVIM-CA (Cardiology), ACVECC

The Animal Medical Center.

Philip.fox@amcny.org; Tel: 1 212 329 8606

Thrombosis is clot formation within a cardiac chamber or vascular lumen. Embolization

results from dislodgement of a clot fragment or other foreign material into a vessel.

PATHOGENESIS

Thrombosis requires one or more of the following conditions: 1) local vessel or tissue injury,

2) circulatory stasis, and 3) altered blood coagulability. The cardiomyopathies predispose to

LA or LV endothelial injury and blood stasis from atrial dilation and impaired function.

Together, these factors predispose cats to thromboembolism. Moreover, collateral

circulation is modulated by vasoactive substances (e.g., serotonin and others) released by the

clot as well as by endothelial substrates. These chemicals decrease collateral circulation and

exacerbate ischemia.

CLINICAL PRESENTATION

Clinical consequences depend upon: 1) site of embolization, 2) severity and duration of

occlusion, 3) degree of functional collateral circulation, 4) state of myocardial function, and

5) development of serious complications. CHF (dyspnea, tachypnea, anorexia) or syncope

may occur concurrently. Clinical signs result from CHF and specific tissues or organs that

are embolized (e.g., azotemia from renal infarction, bloody diarrhea from mesenteric

infarction, posterior paresis from saddle embolus). More than 90% of affected cats present

with lateralizing posterior paresis caused by a saddle clot at the distal aortic trifurcation.

Clinical signs are characterized by the 4 P’s:  Paralysis; Pain; Pulselesness (lack of palpable

femoral arterial pulses); and Polar (e.g., cold distal limbs and pads) extremities.  Anterior

tibial and gastrocnemius muscles become firm  from  ischemic  myopathy by 10 to 12 hours

post aortic embolization.  These soften 24 to 72 hours later.  Acutely affected cats drag their

back legs by flexing and extending the hip but can not flex and extend the hock.  Invariably,

one leg is more severely effected.  Nail beds are cyanotic and distal limbs are swollen.

Embolus to a single brachial artery (usually right front leg) may cause monoparesis. When

intermittent claudication occurs, arterial pulses may be palpated, foot pads feel warm

(normal), and nail beds are not cyanotic. This frequently precedes severe subsequent

thromboembolism. Less common sites include renal, mesenteric, pulmonary, coronary, and

cerebral arteries (embolic “showers”). Most cats are clinically dehydrated and hypothermic.

DIAGNOSTIC WORKUP

Thoracic radiographs, ECG, echocardiogram, biochemical profile, and urinalysis provide the

initial data base. Affected cats have creatine phosphokinase enzymes elevated shortly after

embolization; BUN/creatinine, serum alanine aminotransferase and aspartate

aminotransferase (SGOT) elevate by 12 hours of presentation, and peak by 36 hours post

embolization. Hyperglycemia, mature leukocytosis, lymphopenia, and hypocalcemia may be

present. Acute hyperkalemia can result from skeletal muscle reperfusion injury downstream

from the embolus. Hypokalemia accompanies anorexia and diuretic therapy. Coagulation

abnormalities may occur.  Echocardiography characterized heart structure and function and

detects intracardiac and vascular thrombi. Spontaneous echo contrast (“smoke”) in the LA

or LV is associated with blood stasis, and is a harbinger for increased thromboembolic

risk. Scintigraphy, MRI, high definition CT, and angiography may have clinical application in

some cases.

TREATMENT GOALS

Therapies are directed to 1) manage concomitant CHF or serious arrhythmias (especially

associated with hyperkalemia), 2) patient support (nutritional supplementation, correct

hypothermia, prevent self mutilation), 3) acute pain amelioration, 4) measures to limit

thrombus growth/ formation, 5) critical monitoring, and 6) prevention of repeated events.

Management of Heart Failure

Therapies may include furosemide, supplemental O2 administration, ACE inhibitors,

inotropes or inodilator's, nutraceuticals, arrhythmia control, mechanical fluid removal, and

other measures as needed.

Patient Support

Measures include correction of dehydration, acid/base/electrolyte alterations, hypothermia,

and nutrition. Aspirin during the first 48 hours relieves muscle pain from  ischemic myopathy.

For anorexia, placement of a nasoesophageal feeding tube provides alimentation,

particularly during the first week of therapy. Maintain hydration, electrolyte balance, and

nutritional support.  To prevent self mutilation (excessive licking or chewing) of distal limbs

devitalized by an occlusive saddle embolus which is common during convalescence, apply

a loose-fitting bandage, stockinet, or other barrier.  Avoid indwelling venous catheters into

legs devitalized by embolus.

Pain Management

Pain is usually most intenst within the first 24 hours of thromboembolism and appears to

subside rapidly thereafter. One must take care to avoid excessive medications that would

blunt the ability to clinically assess physical status, mentation, and appetite. Some

commonly used agents include butorphanol (0.2-0.4mg/kg SQ q6-8 hours), hydromorphone

(0.05t0.1mg/kg SQ), or fentanyl patches.

Thrombolytic Therapy

Streptokinase (or urokinase) acts by generating the nonspecific proteolytic enzyme

plasmin through conversion of the proenzyme plasminogen. This causes a generalized lytic

state (beware of bleeding complications). Dose- 90,000IU over 20 minutes followed by

45,000 IU CRI for 2-24h. This therapy has largely fallen out of favor.

Recombinant tissue-type plasminogen activator (p-ta) has a lower affinity for circulating

plasminogen and does not induce systemic fibrinolyisis. It binds to fibrin within the

thrombus, converts entrapped plasminogen to plasmin, and initiates local fibrinolysis.

Severe hyperkalemia occurs in half of treated cats. Dose (cats with thromboembolism)-

0.25 to 1.0 mg/kg/hr IV; total IV dose, 1-10 mg/kg. This therapy has fallen out of favor.

Anticoagulant Therapy

Low molecular weight heparin drugs are added when cats have thromboembolic

complications. Two particular agents, enoxaparin (Lovenox) and  dalteparin (Fragmin), have

received the most attention…

Unfractionated Heparin has largely fallen out of favor. Heparin binds to lysine sites on

plasma antithrombin III, enhancing its ability to neutralize thrombin and activated factors XII,

XI, X, IX, preventing activation of the coagulation process…Compared with

unfractionated heparins, low molecular weight heparins (LMWH) provide greater safety and

bioavailability, longer plasma half life, and can be given as a fixed, daily, subcutaneous

dose….

Coumarin therapy has largely fallen out of favor. It impairs hepatic vitamin K metabolism,

a vitamin necessary for synthesis of procoagulants…Dose- warfarin nitial oral daily dosage (0.25 to 0.5 mg/cat) is adjusted to prolong the PT time to twice the normal value; alternatively, it is adjusted by the international normalization ratio (INR) to maintain a value of 2.0 to 3.0…Some overlap warfarin

and heparin therapies several days…

Critical Monitoring

Hyperkalemia can occur acutely as a result of re-perfusion injury. Continuous ECG

monitoring is valuable during the first 3 days of hospitalization. Periodic evaluation of BUN

and electrolytes during this interval are useful.

Prevention of Repeated Thrombosis Drugs intended to prevent thrombosis include

antiplatelet agents and anticoaguants. Antiplatelet Agents may be considered when there

is severe left atrial enlargement, when spontaneous echo contrast is evident in the LA or

LAV, or when cats have have had  previous thromboembolic episodes.

Aspirin is a commonly use to drug administered…Dose in cats- 25

mg/kg, or 1/4 of a 5-grain tablet q48 - 72h PO effectively inhibits platelet function for 3 to 5

days, and is relatively safe.  Investigators could not demonstrate a survival difference

between high dose (>40mg/cat) versus low dose (5mg/cat) aspirin, although morbidity was

reduced using the low dose.  There is no evidence that aspirin prevents first time or

recurrent thromboembolism.  Adverse effects include anorexia and emesis.

Clopidogrel (Plavix) is a new potent antiplatelet agent currently under evaluation to prevent

or treat arterial thromboembolism…Anti-platelet effects occur by three days post-administration.

Dosage is one quarter of a 75 mg tabletop q 24

hrs. adverse effects can occur in 10% of cases and include anorexia and emesis, and

diarrhea.

Modulation of Hypercoagulability- Hyperhomocysteinemia is a risk factor for

thromboembolism in people and may occur in some cats. Folic acid and B12

supplementation might be beneficial in cats with hyperhomocysteinemia or recovering  from

thromboembolism.

Indicators of a Relatively Favorable Prognosis-Arterial TE

Favorable signs: 1. resolution of CHF and/or control of serious arrhythmias, 2. Lack of

LA/LV thrombi or spontaneous echo contrast, 3. Reestablished appetite, 4. Relatively

normal BUN/creatinine/ ectrolytes, 5. Return of limb viability/function (e.g., loss of swelling;

return of normal limb temperature; return of motor ability), 6. Return of femoral arterial

pulses and pink nail beds, 7. Lack of self mutilation.

Indicators of a Grave Prognosis- Arterial TE

Grave prognosis: 1. Refractory CHF or development of malignant arrhythmias, 2. Acute

hyperkalemia, 3. Declining limb viability (e.g., progressive hardening of gastrocnemius and

anterior tibial muscle group; failure of these muscles to soften 48-72 hours after

presentation; distal limb necrosis), 4. Multiorgan/multisystemic embolization (CNS signs,

bloody diarrhea, acute renal failure), 5. History of previous embolic episodes, 6. Presence

or development of LA/LV thrombus or spontaneous echo contrast, 7. Rising BUN,

creatinine, 8. Disseminated intravascular coagulation, 9. Unresponsive hypothermia, 10.

Severe LA enlargement with tachyarrhythmia.