Evaluation of clopidogrel response in healthy cats using a novel viscoelastic test and thromboelastography.

Introduction: Cats with cardiomyopathy face an increased risk of arterial thromboembolism (ATE). Although clopidogrel is frequently utilized to mitigate this risk, feline responses to this therapy exhibit variability. This study evaluated 2 viscoelastic devices, thromboelastography (TEG) and Viscoelastic Coagulation Monitor (VCM), for monitoring clopidogrel in cats in comparison to light transmission aggregometry (LTA). Methods: Twenty-eight healthy cats received clopidogrel for 7 days. Blood was collected at baseline and after treatment for analysis by TEG, VCM, and LTA. Results: On LTA, maximum amplitude, slope, and area under the curve (AUC) significantly decreased after treatment (p < 0.0001). On VCM, maximum clot firmness (MCF) significantly increased after treatment (p = 0.002). On TEG, R-time significantly prolonged (p = 0.024), while K and alpha angle significantly changed (p = 0.0002 and p = 0.0014, respectively). There was a moderate negative correlation between TEG R-time and LTA AUC (r = -0.39, p = 0.042). Eight cats were identified as non-responders to clopidogrel. Of the 8 non-responders, 6 (75%) had shortened R time after treatment. VCM appeared to be less discriminatory in identifying non-responders. Discussion: LTA remained the gold standard of monitoring clopidogrel treatment in cats. Unexpected changes on VCM and TEG were likely related to high interindividual and assay variability and increased sensitivity of feline platelets. R-time on TEG may have potential utility for point-of-care monitoring of clopidogrel response in cats.

2022 Update of the Consensus on the Rational Use of Antithrombotics and Thrombolytics in Veterinary Critical Care (CURATIVE) Domain 6: Defining rational use of thrombolytics.

OBJECTIVES: To systematically review available evidence and establish guidelines related to the use of thrombolytics for the management of small animals with suspected or confirmed thrombosis. DESIGN: PICO (Population, Intervention, Control, and Outcome) questions were formulated, and worksheets completed as part of a standardized and systematic literature evaluation. The population of interest included dogs and cats (considered separately) and arterial and venous thrombosis. The interventions assessed were the use of thrombolytics, compared to no thrombolytics, with or without anticoagulants or antiplatelet agents. Specific protocols for recombinant tissue plasminogen activator were also evaluated. Outcomes assessed included efficacy and safety. Relevant articles were categorized according to level of evidence, quality, and as to whether they supported, were neutral to, or opposed the PICO questions. Conclusions from the PICO worksheets were used to draft guidelines, which were subsequently refined via Delphi surveys undertaken by the Consensus on the Rational Use of Antithrombotics and Thrombolytics in Veterinary Critical Care (CURATIVE) working group. RESULTS: Fourteen PICO questions were developed, generating 14 guidelines. The majority of the literature addressing the PICO questions in dogs is experimental studies (level of evidence 3), thus providing insufficient evidence to determine if thrombolysis improves patient-centered outcomes. In cats, literature was more limited and often neutral to the PICO questions, precluding strong evidence-based recommendations for thrombolytic use. Rather, for both species, suggestions are made regarding considerations for when thrombolytic drugs may be considered, the combination of thrombolytics with anticoagulant or antiplatelet drugs, and the choice of thrombolytic agent. CONCLUSIONS: Substantial additional research is needed to address the role of thrombolytics for the treatment of arterial and venous thrombosis in dogs and cats. Clinical trials with patient-centered outcomes will be most valuable for addressing knowledge gaps in the field.

Assessment of P2Y12 Inhibition by Clopidogrel in Feline Platelets Using Flow Cytometry Quantification of Vasodilator-Stimulated Phosphoprotein Phosphorylation.

The primary objective of this study was to evaluate a novel flow cytometry-based assay of quantifying platelet phosphorylation of vasodilator-stimulated phosphoprotein (P-VASP) in cats that received clopidogrel treatment. Eight healthy cats received 18.75 mg PO q24h of clopidogrel for 7 days. Prior to and after clopidogrel treatment, blood was collected for ADP-induced light transmission aggregometry (LTA) and P-VASP measurement by flow cytometry. Flow cytometry measurement of P-VASP levels was used to derive platelet reactivity index (PRI) before and after clopidogrel treatment. Based on P-VASP and LTA findings, platelet response to ADP was significantly attenuated after 7 days of clopidogrel treatment. By eliciting the competing platelet pathways of P2Y12 and cAMP using ADP and PGE1, respectively, ADP had no effect on P-VASP levels following clopidogrel treatment (p = 0.94). Clopidogrel also significantly decreased PRI from 28.84 ± 28.52% to 1.69 ± 12.39% (p = 0.0078). PRI on day 8 correlated moderately with the degree of slope inhibition on LTA (r = -0.4, p = 0.4). Flow cytometry analysis of P-VASP is effective at monitoring the inhibitory effects of clopidogrel on feline platelets.

Establishment of a reference interval for a novel viscoelastic coagulometer and comparison with thromboelastography in healthy cats.

BACKGROUND: Viscoelastic analysis provides information on the dynamics and strength of clot formation as well as clot stability. A novel point-of-care viscoelastic test (Viscoelastic Coagulation Monitor Vet, VCM Vet) could be more cost-effective, simpler to use, and more portable than thromboelastography (TEG). OBJECTIVES: The primary aim of this study was to establish a feline reference interval (RI) for the VCM Vet. A secondary aim was to compare VCM Vet analysis with TEG in healthy cats. METHODS: Fifty-six healthy cats were enrolled in this study. Linear regression was completed to determine whether age and CBC parameters were associated with the VCM Vet parameters and if TEG parameters were correlated with VCM Vet data. Statistical significance was set at P < .05. RESULTS: Fifty-three VCM Vet tracings were used to determine RIs for healthy cats. The determined RIs were: clot time (CT) 104-438 seconds; clot formation time (CFT) 104.5-488 seconds; alpha angle (AA) 30.5°-70°; a10 13.8-32.7 VCM units; a20 19.2-40.1 VCM units; maximum clot formation (MCF) 22.5-44.8 VCM units; Lysis Index 30 (Li30) 92.9%-100.9%; and Lysis Index 45 (Li45) 92%-100%. Linear regression identified a strong positive correlation between the CT and R-time measured using the VCM Vet and TEG methods, respectively; no other parameters were correlated. CONCLUSIONS: The use of VCM Vet is feasible in cats, and we determined the first described feline RIs for this test. In general, the VCM Vet data did not correlate with TEG in healthy cats.

Obstructive Tracheal Necrosis in a Dog Secondary to Smoke Inhalation Injury-Case Report.

A 4-year-old Siberian Husky mix was referred to the emergency service of the University of California Davis Veterinary Medical Teaching Hospital after being found unconscious in a housefire. Upon arrival, the dog was conscious and panting with normal breathing effort. The dog was initially treated with oxygen therapy to minimize the risk of carbon monoxide toxicosis. Progressive agitation with paroxysmal episodes of increased respiratory effort and increased upper airway sounds were noted ~48 h after presentation. Hypoxemia was then documented. Clinical signs continued to progress despite supportive measures, and five days after initial presentation mechanical ventilation was deemed indicated. Following anesthetic induction, endotracheal intubation was performed. Capnography and peak inspiratory pressures recorded on the mechanical ventilator were consistent with airway obstruction. Diffuse intraluminal tracheal obstruction with grossly necrotic tracheal tissue was confirmed using fiber optic tracheoscopy. The patient was humanely euthanized due to grave prognosis. At necropsy, the tracheal lumen was obstructed by sloughed, necrotic tracheal mucosa. This is the first report describing a severe delayed intrathoracic large airway complication secondary to smoke inhalation in a dog.