Page 305 - Feline Cardiology

Chapter 20: Arterial Thromboembolism 313

enhancing its ability to neutralize thrombin and acti- However, previous research suggests important
vated factors XII, XI, I, and IX, which prevents activation species differences in the pharmcokinetics of LMWH. In
of the coagulation process. Although heparin has proven particular, compared to humans, the half-life and peak
effective in human trials and experimental animal activity of LMWHs appear to be very different in the cat
models, it has never been evaluated in spontaneously (see the section “Heparins,” below). In any case, for the
occurring feline arterial thromboembolism and reported acute phase of therapy in the hospital (when thrice daily
dosages vary widely. dosing is not cumbersome) they do not offer a signifi-
cant advantage over UF heparin, and are much more
Unfractionated (UF) Heparin costly.
In spite of this limitation, heparin is part of the standard
of care for hospitalized patients during the early, acute Aspirin
stage of ATE because of these theoretic benefits. Heparin Cyclooxygenase (COX) converts arachidonic acid to
should not be administered intramuscularly because of prostaglandin, which is the immediate precursor of
the risk of injection site hemorrhage. In normal cats, a several different products including prostacyclin and
UF heparin dosage of 250–300 U/kg administered sub- thromboxane A2. Prostacyclin is produced in endothe-
cutaneously every 8 hours resulted in acceptable plasma lial cells and effects include inhibition of platelet plug
concentrations (Smith et al. 2004). If the patient is formation and vasodilation; whereas thromboxane A2 is
in shock, the first dose can be administered intrave- a vasoconstrictor, which stimulates activation of new
nously. Because of significant variations in the sensitiv- platelets and increases platelet aggregation. Aspirin
ity of aPTT reagents and the poor correlation between induces a functional defect in platelets by irreversibly
heparin levels and aPTT, some authors do not recom- inhibiting COX and therefore the production of throm-
mend routine monitoring of these values when heparin- boxane A 2 . It is irreversible because platelets have no
izing cats with UF heparin (Smith and Tobias 2004). The DNA, so they are unable to synthesize new COX once Arterial Thromboembolism
ACT is even less predictive of plasma heparin concentra- aspirin has irreversibly inhibited the enzyme. In con-
tions and level of anticoagulation (Smith and Tobias trast, the nucleated endothelial cell will eventually
2004). However, the traditional monitoring recommen- produce increased COX levels because of gene activa-
dation was to maintain the aPTT or ACT at 1.5–2.5 tion. Therefore, aspirin therapy initially has little or no
times the pretreatment value or normal control value effect, but eventually the effect of prostaglandin pre-
(Lunsford and Mackin 2007; Smith et al. 2008). Plasma dominates. This aspirin-induced platelet inactivation is
heparin concentration measured by chromogenic factor irreversible and persists for the life of the platelet, which
Xa assay is more accurate; however, it is not readily avail- is 7–10 days. Although the initial anticoagulant effect is
able to many practices (see the section “Long-Term thought to be negligible with aspirin therapy, cats treated
Management,” below). with oral aspirin 1 hour before thrombus occlusion of
the aorta had better collateral circulation than did those
Low Molecular Weight Heparin (LMWH) cats that did not receive aspirin in an experimental feline
Because small heparin polysaccharides are unable to ATE model (Schaub et al. 1982). Therefore, some clini-
bind thrombin and antithrombin (AT) simultaneously, cians initiate aspirin therapy as soon as the patient is
they are unable to catalyze the inactivation of thrombin stable enough to begin oral medications (Smith 2004).
by AT, but retain the ability to enhance the inhibition of Although not widely recommended, some clinicians
activated factor X and other coagulation factors by AT. have advocated administration of aspirin by the owner
Since there is less anti-II activity, LMWHs do not alter immediately at the onset of clinical signs suggesting ATE.
PT and APTT times, and LMWH level assessment If there is a high index of suspicion of ATE (previously
requires measurement of anti-Xa activity (see the section diagnosed significant heart disease, prior ATE events,
“Heparins,” below). In humans they have more predict- etc.) and oral administration of medications is possible
able bioavailablility, requiring less monitoring of the in a quickly and atraumatic fashion, then administration
patient’s coagulation status and less frequent dosing of ¼ to 1 baby aspirin is unlikely to cause harm.
than UF heparin. Additionally, they are less likely to
cause thrombocytopenia than unfractionated heparin Long-Term Management
(1–2% risk vs 2–5%) (Nutescu et al. 2005). Meta-analyses In retrospective studies, the proportion of affected cats
of the various human trials have concluded that the risk with recurrence of ATE has ranged from 24 to 75 percent
of major bleeding events is also improved using LMWH and was the ultimate cause of death or euthanasia in 20
compared to UFH (0.8–2.2% compared to 2.6–4.7%, to 50 percent of the cats (Smith and Tobias 2004; Smith
Gouin-Thibault et al. 2005). et al. 2004; Lunsford and Mackin 2007). Subjectively, it