Evaluation of clopidogrel responsiveness using the Platelet Function Analyzer-200 (PFA-200) in dogs

Abstract

We aimed to evaluate the prevalence of clopidogrel resistance in hypercoagulable dogs using the Platelet Function Analyzer-200 (PFA-200) P2Y cartridge; further, we aimed to assess the utility of hematocrit (HCT), platelet count (PLT), prothrombin time (PT), activated partial thromboplastin time (aPTT), thromboelastography (TEG) parameters, and D-dimer level as indicators of clopidogrel efficacy. Forty healthy dogs underwent single measurements of P2Y closure time (CT), HCT, PLT, PT, aPTT, TEG parameters, and D-dimer levels, while thirty hypercoagulable dogs underwent two measurements of these parameters before and after clopidogrel treatment. The reference interval for P2Y CT in healthy dogs was 40.0-141.5 s, with a mean of 63.9 ± 26.82 s. Hypercoagulable dogs showed a mean baseline P2Y CT of 77.4 ± 37.6 s. Moreover, 23 (76.67%) and 7 (23.33%) showed responsiveness and resistance to the initial clopidogrel dose, respectively. The mean P2Y CT of the clopidogrel-resistant group after clopidogrel administration was 182.71 ± 78.43 s. Increasing the maintenance dose successfully overcame clopidogrel resistance in these seven dogs. Among the assessed parameters, only D-dimer levels showed a significant decrease in the clopidogrel-responder group (p < 0.05), suggesting its potential utility in evaluating responsiveness. In conclusion, the PFA-200 P2Y cartridge effectively detects clopidogrel resistance in dogs and can guide therapeutic adjustments such as dose escalation.

Keywords: P2Y cartridge; PFA; Platelet Function Analyzer; clopidogrel resistance; dogs.

Figure 1

The Platelet Function Analyzer −200 device used to assess the antiplatelet effects of clopidogrel. Citrate-treated blood is dispensed into the P2Y cartridge.

Figure 2

Box-and-Whisker plots of P2Y closure time (CT) in the healthy and hypercoagulable groups. The boxes indicate the interquartile ranges (25^th–75^th percentile) and lines within the boxes indicate the median values. Whiskers indicate either 1.5 times the interquartile range or the range limit for the data, whichever is less. Circles represent mild outliers, which are values exceeding 1.5 times the interquartile range below the 25th percentile or above the 75th percentile. Asterisks represent extreme outliers, which are values exceeding three times the interquartile range beyond these percentiles. The hypercoagulable group shows prolonged P2Y CT compared to the healthy group (p < 0.05, Mann–Whitney U test).

Figure 3

Pie chart of proportion of dogs by responsive dosage. Among the 30 dogs in the hypercoagulable group, 76.67, 16.67, 3.33, 3.33% of the dogs showed clopidogrel responsiveness at 2 mg/kg, 4 mg/kg, 6 mg/kg, and 8 mg/kg once daily, respectively.