Page 309 - Feline Cardiology

Chapter 20: Arterial Thromboembolism 317

sion in 6 cats. When administered at dosages ranging different (DeFrancesco et al. 2003). Moreover, warfarin
from 18.75–75 mg/cat once daily, clopidogrel resulted in is highly protein-bound in cats and minor shifts in
significant antiplatelet effects and none of the treated albumin status or concurrent use of other, highly
cats developed adverse effects associated with drug protein-bound drugs, may result in massive alterations
administration in this dose range (Hogan et al. 2004). in active drug levels and the degree of anticoagulation
However, in a study designed to determine the utility of (Smith and Tobias 2004). Catastrophic hemorrhage is a
Plateletworks® ADP tubes for use in monitoring clopi- potential complication and the agent is therefore not
dogrel therapy in cats, 33% (3/9) of cats treated with recommended in cats that are allowed outside. The
clopidogrel developed mild diarrhea (Hamel-Jolette reported frequency of fatal hemorrhage in cats treated
et al. 2009). In this study, platelet aggregation was sig- with long-term warfarin is 11% (Smith et al. 2004). Diet
nificantly lower in the clopidogrel treated cats, suggest- and disease state can potentially affect the pharmacoki-
ing the drug is effective in cats. Moreover, Plateletworks® netics of warfarin, which already has an unpredictable
ADP tubes appear to be a viable way to monitor efficacy pharmacokinetic pattern in the cat (Lunsford and
of antiplatelet medications in cats (Hamel-Jolette et al. Mackin 2007). Therefore, regular therapeutic drug mon-
2009). A prospective clinical trial is currently underway itoring and good owner compliance is crucial with this
evaluating clopidogrel in cats with ATE. agent.
Occasionally clopidogrel treated cats may require a Historically, the prothrombin time (PT) is the labora-
surgical procedure. Anecdotal evidence suggests the risk tory test recommended for monitoring warfarin activity.
of bleeding complications is low with this medication. The PT is the result in seconds that it takes the plasma to
However, in a group of normal cats, platelet function clot after addition of tissue factor (which measures the
values returned to baseline 7 days after discontinuing extrinsic and common coagulation pathways). The
therapy whether a high (75 mg q 24 h), moderate amount of time for an individual varies depending on the
(37.5 mg q 24 h), or low (18.75 mg q 24 h) dose of clopi- type of analytical systemic used to perform the test; in Arterial Thromboembolism
dogrel was administered (Hogan 2004). Moreover, no human medicine the international normalized ratio
adverse effect of the drug (or its discontinuation, such (INR) was introduced in the early 1980s to standardize
as rebound hypercoagulability) was noted in this study. results so that comparisons can occur across time and
Therefore, it seems most appropriate to suggest discon- among various laboratories. Warfarin causes an initial
tinuing the drug for a week prior to proceeding with a prothrombotic effect (due to decreased protein C and S
surgical procedure which is elective. levels) and ATE patients receiving warfarin should con-
Abciximab, a glycoprotein IIb/IIIa antagonist, is a tinue to receive heparin the first 4–5 days of treatment to
potent inhibitor of platelet aggregation. This drug was counteract the initial procoagulant effect of warfarin
evaluated in a feline model of arterial injury. Cats in the (Smith and Tobias 2004). Monitoring with INR or PT
abciximab plus aspirin group had significantly greater testing is recommended to be weekly during the first 4
reduction in platelet function than the group of cats weeks of therapy, followed by evaluation every 2 to 3
which received aspirin alone (Bright et al. 2003). months during chronic therapy. The target PT is 1.5 to
However, this drug is not being used routinely in ATE 2.5X normal, whereas an INR of 2.0–3.0 is generally rec-
cats at this time. ommended in cats (Smith and Tobias 2004, Lunsford and
Mackin 2007). Despite small changes in dose, there are
Vitamin K Antagonists: Warfarin often large changes in PT making a dose-dependent pre-
Warfarin (Coumadin) impairs hepatic vitamin K metab- diction of anticoagulant effect challenging. Additionally,
olism, a vitamin necessary for synthesis of procoagu- there is significant risk of hemorrhage, and if pulmonary
lants (factors II [prothrombin], VII, IX, X) as well as hemorrhage occurs it can be difficult to differentiate
regulatory proteins C and S through its inhibition of from CHF and pulmonary edema. Considering the risk
vitamin K epoxide reductase. Warfarin therapy does not of complications to warfarin therapy and the cost of
appear to reduce the risk of ATE recurrence over aspirin therapeutic drug monitoring, warfarin is not typically
therapy (Smith and Tobias 2004). One study, which recommended for therapy of ATE cats.
compared warfarin and a LMWH (dalteparin) in 31 ATE
cats, reported a median survival time of 69 days and Heparins: Unfractionated (UF) and Low
24% recurrence of ATE in the 17 cats treated with war- Molecular Weight Heparin (LMWH)
farin (DeFrancesco et al. 2003). Three cats treated with For chronic therapy, UF heparin has traditionally not
warfarin had bleeding complications compared to no been used commonly in veterinary medicine because
reported complications in dalteparin-treated cats. The it requires frequent parenteral administration every
survival curves for the 2 groups were not significantly 6–8 hours. In humans, LMWHs require less frequent