Page 354 - Clinical Small Animal Internal Medicine

322 Section 4 Respiratory Disease

and thrombin. Thus, LMWHs are principally anti‐FXa rivaroxaban has been studied in dogs, and it is reported
VetBooks.ir agents and are probably best monitored with anti‐Xa to be an effective anticoagulant in healthy dogs. Its clini­
cal use has been reported in a small case series, but it has
assays, although tissue factor (TF)‐activated TEG can
also be used. LMWHs are less protein bound than UFH,
The oral prodrug dabigatran etexilate is a potent,
and have more predictable PK profiles and better bioa­ not been evaluated in a randomized clinical trial.
vailability after SC injection. The PK profiles of distinct reversible direct thrombin inhibitor. This class of drugs
LMWHs preparations are not interchangeable, however. do not require AT as a co‐factor for their anti‐IIa activity
LMWH PKs have been evaluated in normal healthy dogs and are also able to inhibit thrombin bound to formed
and therapeutic anti‐Xa levels extrapolated from people clot. Dabigatran can be monitored with the PT, aPTT or
are achievable. LMWH PKs in cats are less predictable, the preferred ecarin clotting time (ECT) in canine
however, with frequent administration of high dosages plasma. Dabigatran is FDA approved for thromboembo­
necessary to achieve target anti‐FXa activities. A recent lism in AF and in other countries for VTE and has a simi­
study evaluated the ex vivo antithrombotic effect of lar efficacy and safety profile to warfarin for the treatment
enoxaparin in a venous stasis model in cats, comparing it of acute symptomatic VTE. To date, no studies have
to anti‐Xa activity. The study found that at peak (but examined the effects of dabigatran in small animals.
not at trough) plasma levels, enoxaparin significantly
reduced thrombus formation, but in this model there Antiplatelet Agents
was little correlation between antithrombotic effect and In small animals, antiplatelet agents are principally used
anti‐Xa activity. Clearly, well‐designed clinical studies for long‐term oral maintenance therapy or as thrombo­
evaluating LMWH in naturally occurring PTE in dogs or prophylaxis for at‐risk patients. Oral antiplatelet agents
cats are urgently needed. available for small animals include aspirin, ticlopidine,
Fondaparinux is a synthetic, AT‐dependent selective and clopidogrel, although concerns over myelotoxicity
FXa inhibitor with no anti‐FIIa activity. In people with associated with ticlopidine have led to it being largely
acute PTE, fondaparinux administration reduces PTE superseded by clopidogrel. There is limited evidence of
recurrence rate compared with UFH without increases efficacy for either aspirin or clopidogrel in veterinary
in major bleeding, and is at least as effective as enoxapa­ medicine, however.
rin in this setting. In dogs to date, fondaparinux has only The COX‐1 inhibitor aspirin irreversibly inhibits
been studied in experimental settings. In cats, a recent platelet thromboxane A 2 (TXA 2 ) synthesis, inhibiting
dose‐finding study found that SC administration of platelet function. Aspirin is the primary antithrombotic
0.06–0.20 mg/kg q12h was sufficient to achieve peak therapy for people with atherosclerotic disease, but the
plasma anti‐Xa activity deemed therapeutic in humans. populations of small animals which would most benefit
Warfarin is an oral anticoagulant that inhibits vitamin from aspirin therapy are unknown. Aspirin has been rec­
K epoxide reductase, interrupting the recycling of vita­ ommended for dogs with protein‐losing nephropathy,
min K epoxide to hydroquinone and depleting the nephrotic syndrome, and IMHA. The use of aspirin in
supply of carboxylated clotting factors II, VII, IX, and X. IMHA is contentious, however.
Warfarin is the mainstay for oral anticoagulation in peo­ To date, no studies have been performed in veterinary
ple but maintaining adequate anticoagulation without medicine evaluating the efficacy of aspirin against objec­
hemorrhagic complications is challenging. The drug tive measures of thrombosis or comparing the efficacy of
has a narrow therapeutic index, variable patient dose– aspirin against other antithrombotic therapies, but one
response and numerous interactions with other drugs, such study is reportedly under way. The dose required to
necessitating close therapeutic monitoring. As a result, cause in vitro or ex vivo inhibition of canine platelet
the Consensus on the Rational Use of Antithrombotics function varies with the assay used, but is in the range of
in Veterinary Critical Care (CURATIVE) guidelines pub­ 0.5–20 mg/kg. This wide range may be related to herita­
lished in January 2019 advise against the use of warfarin ble variability in canine thromboxane responsiveness. A
in small animals. recent study suggested that 1 mg/kg/day aspirin consist­
The difficulties associated with the clinical use of vita­ ently inhibited platelet function in only a third of dogs
min K antagonists generated a need for effective, safe, and higher dosages may be required to obtain a consist­
novel oral anticoagulants. Rivaroxaban is an oral, small ent effect.
molecule, direct FXa inhibitor that can inhibit both free The thienopyridines ticlopidine and clopidogrel are
and prothrombinase complex‐associated FXa. This drug both produgs that rely on active metabolites for their
can be monitored using the PT or aPTT. Rivaroxaban in vivo efficacy. The active metabolite of clopidogrel
was recently approved by the FDA for PTE following causes cumulative inhibition of platelet function follow­
demonstration of equivalent efficacy to standard therapy ing repeated daily administration. In humans, clopi­
with enoxaparin and warfarin. The pharmacokinetics of dogrel may be marginally more effective than aspirin,