PREVENTION

No strong recommendations exist for one particular prophylaxis strategy. Several drugs have been used to inhibit the coagulation cascade or platelets. These drugs have been used as single agents and in combination.

Warfarin

Pharmacodynamic studies in healthy cats suggest a dose of 0.06 to 0.09 mg/kg/day given orally.⁴¹ Patients must undergo anticoagulant therapy with heparin before starting warfarin therapy since inhibition of proteins C and S occurs first and may make patients initially hypercoagulable.³⁴ No prospective randomized studies have been conducted on the efficacy of warfarin in cats with thromboembolic disease to justify its use since it has potential to produce lethal bleeding complications.

Heparin

Long-term heparin therapy is best accomplished with LMWH. Two products approved for use in people, Dalteparin (Fragmin—Eisai) and enoxaparin (Lovenox—Sanofi-Aventis), are used most commonly in cats to prevent ATE. Owners can be taught to give the injections at home just as with an insulin injection.

Current dosing guidelines are 100 U/kg twice daily subcutaneously for dalteparin and 1 mg/kg subcutaneously twice daily for enoxaparin.⁹ One retrospective study showed LMWH to be well-tolerated and resulted in minimal bleeding complications at a median dose of 99 U/kg.⁴² However, recent studies have shown that LMWH is rapidly absorbed and eliminated in healthy cats.^43,44 These findings call into question the current dosing scheme. The dose and frequency may need to be increased. Therapy can be monitored by measuring anti-Xa activity after achieving a steady state 48 hours after initiating therapy. Although LMWH appears to be safe and well-tolerated in cats, no prospective randomized trials have been conducted to determine its effectiveness in preventing ATE.

Aspirin

Aspirin has been used for many years in virtually every thromboembolic disease process. Aspirin irreversibly inhibits platelets through inhibition of thromboxane A₂ synthesis.⁴⁵ Low-dose aspirin has been recommended in people to prevent potential hypercoagulability resulting from prostacyclin inhibition with higher (conventional dose) aspirin.⁴⁵ Low-dose aspirin is inexpensive, fairly safe, and usually well-tolerated in cats. Doses range from 5 to 20.25 mg/cat every 72 hours.² This low dose has been shown to produce similar survival time and recurrence rates with fewer side effects compared with higher doses.²

Thienopyridines

The thienopyridines are a new class of platelet inhibitors that act through antagonism of the adenosine diphosphate receptor.⁴⁶ Antagonism of adenosine diphosphate inhibits serotonin production and may preserve collateral circulation and decrease the severity of signs in cats that develop repeat thromboembolic episodes. The two drugs in this class that have been used in cats are clopidogrel (Plavix—Bristol-Myers Squibb/Sanofi-Aventis) and ticlopidine (Ticlid—Roche Laboratories). Clopidogrel has a less severe side effect profile in people than ticlopidine has, consisting of mainly gastrointestinal signs.⁴⁶

Both drugs have been studied in cats. A small study of ticlopidine in cats found it to be effective in impairing platelet function, but its use in cats is not recommended because of dose-dependent gastrointestinal signs.⁴⁷ Clopidogrel has also been shown to be effective at decreasing platelet aggregation in cats at a dose of 18.75 mg/cat given orally every 24 hours.^48,49 The ongoing FATCAT study is a double-blinded multi-site study evaluating the comparative efficacy of clopidogrel vs. conventional-dose (81 mg/cat every 72 hours) aspirin in preventing ATE recurrence, which should provide good information about the relative efficacy of these two pharmacotherapeutic approaches (http://www.vin.com/fatcat/).