Page 310 - Feline Cardiology

318 Section H: Arterial Thromboembolism

administration and there has been interest in using these The optimal protocol in cats for thromboprophylaxis or
products in cats with ATE. However, current evidence thrombosis treatment remains unclear and additional
suggests that the LMWHs currently on the market, dalte- studies are warranted. Moreover, the effects of LMWH
parin and enoxaparin, require more frequent parenteral and/or fondaparinux in cats with disease will need to be
administration than once daily. In a study of healthy cats, better evaluated with clinical trials that use outcome
administration of 100 IU/kg dalteparin SC twice daily measures before efficacy is definitively ascertained.
and enoxaparin at 1 mg/kg SC twice daily failed to induce Currently, the cost may be as high as several hundred
sustained anti-Xa activity that was significantly different dollars a month, but it can often be acquired interna-
from baseline, placebo, or UF heparin. However, cats tionally for a lower cost. This comparatively higher cost,
treated with UF heparin consistently attained anti-Xa and the likely frequent administration that will be
activity within or above the therapeutic range (Alwood required, may make this therapeutic option nonviable
et al. 2007). This result was further substantiated by a for many pet owners. Moreover, whether using UF
pharmacokinetic model for enoxaparin in the cat, pre- heparin or LMWH, bleeding is a possible complication.
sented by the same group, which suggests that both Therefore, jugular venipuncture and/or cystocentesis
dosage and dosing interval of LMWH would need to be should probably be avoided in these patients.
increased in the cat to maintain the anti-Xa within the An additional benefit of LMWHs in human medicine
target zone and suggested a dose of 1.5 mg/kg and q 12 h or is that, because of its more predictable bioavailability
more frequent dosing interval. Another group reported in this species, routine monitoring is recommended
only in certain populations who are at risk of hemor-
similar results in 8 healthy cats. In this study, 100 IU/kg
Arterial Thromboembolism healthy cats twice daily for 13 doses. Four of the treated does not bind to thrombin, it has little impact on the
rhage (the elderly, pregnant, etc.). Because LMWH
of dalteparin was administered subcutaneously to 8
aPTT. Measurement of factor Xa inhibitory activity
cats developed anti-Xa activity within the proposed
therapeutic range (0.3–0.6 U/ml) at one time point.
(anti-Xa assay) is considered the standard laboratory
test for monitoring LMWH activity, usually at peak
However at other time points in these cats, and at all time
activity in humans. Considering the rapid absorption
points in the other 4 cats, anti-Xa activity was only trace
or not measurable, suggesting that although LMWH
may be useful therapeutically, the optimum dose has yet
it is advisable to monitor drug effect in patients in
which this treatment regime is chosen to ensure an
to be determined (Vargo et al. 2009). It is likely that drug and elimination kinetics of LMWH in normal cats,
effects in cats with cardiomyopathy or other predispos- appropriate drug level is achieved. The Cornell University
ing factors to thrombosis will be different than those Department of Population Medicine and Diagnostic
effects seen in normal cats, and studies in this population Sciences Comparative Coagulation Service (http://
are warranted. However, a previously published retro- www.diaglab.vet.cornell.edu/coag/) offers comprehen-
spective study, which used once or twice daily dosing sive coagulation tests including the anti-Xa activity level,
with dalteparin, was unable to show that therapy reduced which is the gold standard assay.
the recurrence rate of ATE (Smith et al. 2004). A third- An alternative for monitoring LMWH activity appears
generation heparin medication has also been evaluated to be thromboelastography (TEG). TEG is a bedside
in healthy cats (Fiakpui et al. 2010). Fondaparinux is a blood test that can be used to define viscoelastic proper-
homogenous synthetic pentasaccharide preparation, ties of blood. The cost of equipment has limited its
which has antithrombotic effects confined to Xa inhibi- widespread availability in veterinary medicine to date;
tion. Based on a pharmacokinetic model, two doses were however, new and used units are becoming increasingly
evaluated in healthy cats over a 7-day period: 0.06 mg/kg accessible. At this time, equipment is rarely available
SC q 12 hours (thrombophrophylactic dose) and 0.2 mg/kg outside the academic and large (referral) private practice
SC q 12 hours and 0.2 mg/kg SC q 12 hours (thrombosis setting.
treatment). The thromboprophylactic protocol approxi- Conventional coagulation tests typically evaluate one
mated median peak and trough antiXa activities seen in portion of the coagulation system; however, TEG is a
humans considered effectively treated with fonaparinux. technique that provides information about the entire
The higher dose approximated only peak activities con- coagulation system (Donahue and Otto 2005).
sistent with effective treatment in humans. The higher Specifically, TEG provides information regarding plate-
fondaparinux regimen altered some thromboelastogra- let activation, fibrin formation, and clot retraction
phy variables (increased R and K, decreased α-angle and (Klein et al. 2000), deriving data from the quality of the
MA), but not platelet aggregation studies. No significant clot as well the dynamics of its formation (Donahue and
thromboelastography (TEG) or platelet aggregation Otto 2005). The TEG-generated tracing is called the
effect was noted with the lower dose (Fiakpui et al. 2010). thromboelastogram and consists of 3 zones (Figure