Page 257 - Small Animal Internal Medicine, 6th Edition

CHAPTER 12 Thromboembolic Disease 229

by anti-Xa activity (see Box 12.3). Optimal anti-Xa activ- is human recombinant tissue plasminogen activator (rt-PA).
ity level in cats is not known; the target range in people is rt-PA is a single-chain polypeptide serine protease with a
VetBooks.ir reported as 0.5 to 1 U/mL, although 0.3 to 0.6 U/mL has also higher specificity for fibrin within thrombi and a low affinity
for circulating plasminogen. The risk of hemorrhage is there-
been used.
The LMWH products have differences in biologic and
vators such as streptokinase and urokinase. However, there
clinical effects and are not interchangeable. The most effec- fore less with rt-PA than with nonspecific plasminogen acti-
tive dosage for the various LMWH products is not clearly remains the potential for serious bleeding, reperfusion
established in dogs and cats. Commonly used dosages of injury, and neurologic adverse effects. rt-PA also is poten-
dalteparin sodium and enoxaparin (see Box 12.3) have been tially antigenic in animals because it is a human protein.
extrapolated from human use. Although enoxaparin pro- Veterinary experience with rt-PA is limited, it is relatively
duces anti-Xa activity close to target range at 4 hours post- expensive, and the optimal dosage is not known; the most
dose in cats, activity is generally undetectable 8 hours later. commonly used dose is 5 mg per cat, generally given as a
This finding led to the presumption that higher and more front-loaded IV infusion over 1 to 2 hours (see Box 12.3). In
frequent doses should be used to maintain anti-Xa levels a case series of 11 cats with ATE, rt-PA administration was
closer to human target range. However, this rationale is dis- associated with improved limb function and return of pulses;
puted because it does not appear necessary to maintain peak however, there was a high rate of adverse effects related to
or target anti-Xa levels throughout the dosing period. Indeed, reperfusion injury (azotemia, hyperkalemia, and neurologic
an experimental study of enoxaparin in a modified venous signs), and mortality was high. Thus although rt-PA can
stasis model in healthy cats showed no correlation between effectively break down clots, a clear survival advantage has
antithrombotic effect and anti-Xa levels; in this model, anti- not been shown. If used, this therapy is best instituted within
thrombotic effect of enoxaparin lasted >12 hours. The 3 to 4 hours of vascular occlusion. An intensive care setting,
optimal therapeutic range in cats and the most effective including frequent monitoring of serum potassium concen-
dosage in cats with ATE remain unknown. LMWHs are rela- tration, acid-base status, and electrocardiogram (ECG), is
tively expensive and require owner compliance to administer important to detect reperfusion-induced hyperkalemia and
SC injections every 12 to 24 hours. metabolic acidosis. The risk-to-benefit profile of thrombo-
Warfarin was historically the most common long-term lytic treatment may be more favorable in patients with brain,
anticoagulant treatment for cats with ATE. However, due to renal, or splanchnic thromboembolism. Other thrombolyt-
serious risk of bleeding, requirement for frequent monitor- ics, including the nonspecific plasminogen activators strep-
ing, and availability of alternative anticoagulants (including tokinase and urokinase, are associated with even more severe
LMWH), warfarin is now rarely used in cats. Warfarin is still side effects and higher mortality, and are not currently
sometimes used in large dogs with systemic TE (see pg. 232) recommended.
if other agents are cost-prohibitive. Surgical thromboembolus removal is typically not advised
A number of new anticoagulant drugs have been devel- in cats. The surgical risk is high, and significant neuromus-
oped for human use and are becoming available for veteri- cular ischemic injury is likely to have already occurred by
nary patients. In people, these drugs offer similar or improved the time of surgery. Percutaneous clot removal using an
antithrombotic efficacy compared with warfarin, with fewer embolectomy catheter has not been effective in cats.
side effects. Synthetic factor Xa inhibitors (e.g., rivaroxaban, In general, the prognosis for cats with ATE is poor. Many
apixiban, fondaparinux) potentiate effects of AT without cats are euthanized on presentation (approximately 1 3 of
affecting thrombin or platelet function. Their effect is moni- cats in reports from tertiary care facilities, and nearly 2 3
tored via anti-Xa activity measurement because they do not of cats in a primary care setting). Of cats where treatment is
affect results of routine coagulation tests. Fondaparinux is attempted, approximately half survive the initial ATE episode
given SC, whereas apixaban and rivaroxaban are both oral. regardless of therapy chosen (conservative or thrombolytic).
Doses for rivaroxaban, apixaban, and fondaparinux in cats Survival is better if only one limb is involved and/or if some
have been published based on pharmacokinetics and anti-Xa motor function is preserved at presentation. Hypothermia
activity in healthy cats; however, clinical efficacy in cats with and CHF at presentation are both associated with poor sur-
ATE has yet to be investigated. Dabigatran etexilate is an oral vival in cats. Other negative factors can include hyperphos-
direct thrombin inhibitor; use of this medication has not phatemia, progressive hyperkalemia or azotemia, bradycardia,
been reported in veterinary medicine. persistent lack of motor function, progressive limb injury
All treatments for ATE discussed thus far are supportive (continued muscle contracture after 2-3 days, necrosis),
rather than directed therapy; the common approach is essen- severe LA enlargement, presence of intracardiac thrombi or
tially to support the cat while the patient’s own intrinsic spontaneous contrast (“swirling smoke”) on echocardio-
fibrinolytic system breaks down the embolus, rather than gram, DIC, and history of previous ATE. Significant embo-
pursuing treatment specifically aimed at dissolving the clot. lization of the kidneys, intestines, or other organs carries a
However, thrombolytic drugs that directly promote clot lysis grave prognosis.
are available. These medications increase conversion of plas- Barring complications, limb function should begin to
minogen to plasmin, thus facilitating fibrinolysis. The most return within days to a week. Some cats become clinically
commonly used thrombolytic agent in veterinary medicine normal within 1 to 2 months, although residual deficits can