title: Establishment of reference ranges and evaluation of in vitro concentration-dependent platelet inhibition by acetylsalicylic acid for multiple electrode impedance aggregometry in healthy dogs.
abstract: Acetylsalicylic acid (ASA, aspirin) is an antiplatelet medication used for prevention of thromboembolism. Effects of ASA appear to vary widely between dogs, but the underlying mechanisms are not understood. The Multiplate analyzer is a newer form of whole-blood impedance aggregometry recently validated for use in healthy dogs. A method utilizing this instrument to measure ASA effects on platelet function has not been established. The goals of this study were to establish reference ranges for the Multiplate in healthy dogs and secondly, to develop a technique to determine the in vitro concentration of ASA needed to cause 50% inhibition of platelet aggregation (IC50). Reference ranges established from 40 dogs at multiple test times for three agonists were consistent with previously published values. In vitro IC50 values were calculated using the sigmoid Emaxmodel in 20 healthy dogs on two occasions to determine individual repeatability. Calculated in vitro IC50 demonstrated four ASA response groups: responder (n = 16), poor responder (n = 1), variable responder (n = 2), and nonresponder (n = 1). Multiplate within-assay variability was  <10% for area under the curve (AUC), and between-assay baseline AUC variability was  <15%. The described technique allowed for determination of an in vitro IC50 for ASA in dogs using a multiple electrode impedance aggregometer.
authors.affiliation: Program in Individualized Medicine (PrIMe), Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
authors.forename: J M
authors.identifier: http://orcid.org/0000-0002-8066-838X
authors.initials: JM
authors.lastname: Haines
authors.affiliation: Program in Individualized Medicine (PrIMe), Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
authors.forename: P M
authors.identifier: http://orcid.org/0000-0001-6003-0496
authors.initials: PM
authors.lastname: Lee
authors.affiliation: Program in Individualized Medicine (PrIMe), Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Hegedus
authors.affiliation: Program in Individualized Medicine (PrIMe), Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Hwang
authors.affiliation: Program in Individualized Medicine (PrIMe), Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Court
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D005260:Female; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D012016:Reference Values
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin