Page 256 - Small Animal Internal Medicine, 6th Edition

228 PART I Cardiovascular System Disorders

may be pharmacogenomic differences in individual cats’ veterinary patients. Abciximab was shown to improve arte-
ability to biotransform clopidogrel, resulting in clopidogrel rial flow in cats with experimentally induced arterial throm-
VetBooks.ir “nonresponders”; the clinical implications of this finding bosis but interestingly did not reduce platelet aggregation
in vitro. Eptifibatide effectively reduced platelet aggregation
remain unclear. The recommended oral dose is 18.75 mg/cat
once daily (or 2-4 mg/kg once daily); maximal antiplatelet
given systemically to cats. Further research is needed before
effects occur within 72 hours and disappear about 7 days in vitro but caused cardiovascular collapse and death when
after drug discontinuation. A loading dose of 75 mg/cat these new drugs are added to the veterinary repertoire.
given as soon as possible after an acute ATE event might also In addition to antiplatelet therapy, anticoagulation with
confer vasomodulating effects that improve collateral blood heparin is used in treatment of acute ATE. Heparin is indi-
flow, and short-term administration of this dose appears to cated to limit extension of existing thrombi and prevent
be well tolerated. Clopidogrel does not cause GI ulceration, additional thrombus formation; it does not promote throm-
as aspirin can; however, a single cat receiving clopidogrel in bolysis. Unfractionated heparin and a number of low-
the FATCAT trial developed a reversible icterus. Vomiting molecular-weight heparin (LMWH) products are available.
does occur in some cats, and the tablets taste very bitter. This Heparin’s main anticoagulant effect occurs through AT acti-
can be ameliorated by giving the drug with food or in a vation, which in turn inhibits FIXa, FXa, FXIa, FXIIa, and
gelatin capsule. FIIa (thrombin). Unfractionated heparin binds thrombin
Aspirin (acetylsalicylic acid) previously was employed to and AT. Optimal dosing protocols for animals are not known.
block platelet activation and aggregation in cats with, or at For acute ATE, unfractionated heparin is usually given as an
risk for, ATE. Aspirin irreversibly inhibits cyclooxygenase, initial IV bolus (often 100 U/kg) followed by either a con-
which reduces prostaglandin and thromboxane A 2 synthesis tinuous rate infusion or SC injections (see Box 12.3). Heparin
and therefore could reduce subsequent platelet aggregation, is not given IM because of the risk for hemorrhage at the
serotonin release, and vasoconstriction. Because platelets injection site. Unfractionated heparin treatment is continued
cannot synthesize additional cyclooxygenase, this reduction until the patient is stable and has been on antiplatelet therapy
of procoagulant prostaglandins and thromboxane persists for a few days.
for the platelet’s life span (7-10 days). Endothelial production Monitoring the patient’s activated partial thromboplastin
of prostacyclin (also via the cyclooxygenase pathway) is time (aPTT) has been recommended, although results may
reduced by aspirin but only transiently as endothelial cells not accurately predict serum heparin concentrations; pre-
synthesize additional cyclooxygenase. Adverse effects of treatment coagulation testing is done for comparison, and
aspirin tend to be mild, unless overdosed, and usually relate the goal is to prolong the aPTT to 1.5 to 2.0 times baseline.
to signs of GI upset or ulceration, mainly as anorexia and Monitoring of anti-Xa activity could be a more accurate
vomiting. The optimal dose is unclear. Cats lack an enzyme means of assessing heparin therapy. Hemorrhage is the
(glucuronyl transferase) necessary to metabolize aspirin, so major complication of heparin therapy. Protamine sulfate
less frequent dosing is required compared with dogs. Aspi- can be used to counteract heparin-induced bleeding;
rin’s efficacy at clinical doses in acute ATE is unknown. In however, an overdose of protamine can paradoxically cause
cats with experimental aortic thrombosis, high-dose aspirin irreversible hemorrhage. Dosage guidelines for protamine
(100 mg/kg) inhibited platelet aggregation and improved sulfate are as follows: 1 mg/100 U of heparin is given slowly
collateral circulation, but this dose would be toxic in a clini- IV if the heparin was given within the previous 30 minutes;
cal setting. The commonly used dose of 10 to 25 mg/kg 0.5 mg/100 U of heparin is given if the heparin was given
(81 mg/cat) q72h does inhibit platelet aggregation in vitro, more than 30 but fewer than 60 minutes earlier; and
but the clinical benefit for treatment or prevention of ATE 0.25 mg/100 U of heparin is given if more than 1 hour has
has not been established. In cats with ATE, there was no elapsed since heparin was administered. Fresh-frozen plasma
difference in outcome for cats receiving low-dose aspirin might be necessary to replenish AT in cases of heparin
(5 mg/cat q72h) compared with more typical doses overdose.
(40-81 mg/cat q48h), and fewer GI side effects were seen at For long-term treatment, LMWH is a safer and more
the lower dose. However, given the superiority of clopidogrel practical alternative to unfractionated heparin. LMWH
(18.75 mg/cat q24h) compared with aspirin (81 mg/cat products are a diverse group of depolymerized heparin that
q72h) in the FATCAT trial, clopidogrel now should be the vary in size, structure, and pharmacokinetics. Their smaller
first-line antiplatelet for treatment or prevention of ATE in size prevents simultaneous binding to thrombin and AT.
cats. Aspirin could be used for cats that fail to tolerate clopi- LMWH products have more specific effect against factor
dogrel, or possibly as an adjunct antiplatelet in addition to Xa and have minimal ability to inhibit thrombin, thus are
clopidogrel. less likely to cause bleeding. LMWH products have greater
Several new antiplatelet medications have been developed bioavailability and a longer half-life than unfraction-
recently for use in people. These include later-generation ated heparin when given subcutaneously because of lesser
P 2Y12 platelet inhibitors, such as prasugrel (a third-generation binding to plasma proteins, as well as endothelial cells and
thienopyridine) and ticagrelor (a nonthienopyridine), as well macrophages. However, LMWH products do not mark-
as the GPα IIb β 3 receptor antagonists abciximab and eptifi- edly affect coagulation times, so aPTT cannot be used to
batide. Prasugrel and ticagrelor have yet to be evaluated in monitor LMWH. LMWH effect can be monitored indirectly