Novel approach to assessment of efficacy of platelet inhibition by clopidogrel and aspirin in healthy dogs
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[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI--COLUMBIA AT REQUEST OF AUTHOR.] Introduction: Antiplatelet therapy, including clopidogrel and aspirin, is used to decrease the risk of thromboembolism in dogs. However, efficacy of therapy is not typically confirmed in clinical patients, nor is therapy able to be titrated to effect based on typical diagnostics. Methods: Six client owned healthy dogs, weighing 21.1-36.4 kg and being between 1-6 years of age were enrolled in a prospective cross over design study. Each dog had baseline lab work and coagulation testing performed, including thromboelastography with platelet mapping (TEG-PM) and whole blood platelet aggregometry (WBPA). Clopidogrel (2-3 mg kg-1), aspirin (2 mg kg-1), or a combination of the two medications were administered for two weeks, with a two week wash out period between each treatment. TEG-PM, WBPA, platelet count, fibrinogen, and packed cell volume (PCV) with total solids (TS) was performed after each treatment. Platelet function was assessed with WBPA. Percentage platelet inhibition was calculated with TEG-PM to evaluate for response to antiplatelet therapy, and level of agreement was determined between TEG-PM and WBPA. Dogs were assessed for drops in PCV, TS, and platelet count or increase in fibrinogen following each treatment. A Shapiro-Wilk test for normality of distribution was performed on all baseline lab work, and a Wilcoxon paired ix rank sum test was performed to evaluate for significant decrease in PCV, TS, or platelets or significant increase in fibrinogen. Significance was determined if p < 0.05. Percentage agreement between TEG-PM and WBPA was also determined. Results: All dogs were aspirin responders on WBPA; 3/6 were clopidogrel responders. There was a poor level of agreement between WBPA and TEG-PM, with these diagnostics showing agreement in 16.7-66.7% of measurements. Clopidogrel treatment produced a significant drop in PCV (p = 0.017); aspirin and clopidogrel treatment in combination caused a significant increase in fibrinogen (p = 0.046) and decrease in TS (p = 0.027). Conclusions: TEG-PM did not consistently identify responders to antiplatelet drugs in healthy canine subjects. There was a poor level of agreement between WBPA and TEG-PM in detecting platelet inhibition from antiplatelet therapies. Though there was a statistically significant decrease in PCV with clopidogrel therapy alone and an increase in fibrinogen with a decrease in TS on combination therapy, the degree of alterations is likely not biologically important in healthy dogs.
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