Sunday, July 24, 2011
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.firstname.lastname@example.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.
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
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.
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
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.
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 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.
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.
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
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…
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
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
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.