Establishment of reference ranges and evaluation of in vitro concentration‐dependent platelet inhibition by acetylsalicylic acid for multiple electrode impedance aggregometry in healthy dogs
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 valida...
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| Veröffentlicht in: | Journal of veterinary pharmacology and therapeutics 2017-12, Vol.40 (6), p.618-628 |
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| container_title | Journal of veterinary pharmacology and therapeutics |
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| creator | Haines, J. M. Lee, P. M. Hegedus, R. M. Hwang, J. K. Court, M. H. |
| description | 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 Emax model 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 |
| doi_str_mv | 10.1111/jvp.12405 |
| format | Article |
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M. ; Lee, P. M. ; Hegedus, R. M. ; Hwang, J. K. ; Court, M. H.</creator><creatorcontrib>Haines, J. M. ; Lee, P. M. ; Hegedus, R. M. ; Hwang, J. K. ; Court, M. H.</creatorcontrib><description>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 Emax model 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.</description><identifier>ISSN: 0140-7783</identifier><identifier>EISSN: 1365-2885</identifier><identifier>DOI: 10.1111/jvp.12405</identifier><identifier>PMID: 28387027</identifier><language>eng</language><publisher>England</publisher><subject>Animals ; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage ; Anti-Inflammatory Agents, Non-Steroidal - pharmacology ; Aspirin - administration & dosage ; Aspirin - pharmacology ; Blood Platelets - drug effects ; Dogs ; Dose-Response Relationship, Drug ; Electric Impedance ; Female ; Male ; Platelet Aggregation - drug effects ; Reference Values</subject><ispartof>Journal of veterinary pharmacology and therapeutics, 2017-12, Vol.40 (6), p.618-628</ispartof><rights>2017 John Wiley & Sons Ltd</rights><rights>2017 John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2405-5066d01ebcce10cd16534fc56778c71a38d36cbc43c8db373b8eb3ce2ce30c333</citedby><orcidid>0000-0001-6003-0496 ; 0000-0002-8066-838X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjvp.12405$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjvp.12405$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28387027$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Haines, J. M.</creatorcontrib><creatorcontrib>Lee, P. M.</creatorcontrib><creatorcontrib>Hegedus, R. M.</creatorcontrib><creatorcontrib>Hwang, J. K.</creatorcontrib><creatorcontrib>Court, M. H.</creatorcontrib><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</title><title>Journal of veterinary pharmacology and therapeutics</title><addtitle>J Vet Pharmacol Ther</addtitle><description>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 Emax model 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.</description><subject>Animals</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - administration & dosage</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</subject><subject>Aspirin - administration & dosage</subject><subject>Aspirin - pharmacology</subject><subject>Blood Platelets - drug effects</subject><subject>Dogs</subject><subject>Dose-Response Relationship, Drug</subject><subject>Electric Impedance</subject><subject>Female</subject><subject>Male</subject><subject>Platelet Aggregation - drug effects</subject><subject>Reference Values</subject><issn>0140-7783</issn><issn>1365-2885</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1u1DAYhi1ERYfCggsgL2GR1o7zY5aoKgVUqV0A28j5_CXjyomD7UyVHUfgCL0KHIWT4MwUdrVkWZYfP7bel5BXnJ3yNM5ud9MpzwtWPiEbLqoyy6Usn5IN4wXL6lqKY_I8hFvGmJCcPyPHuRSyZnm9Ib8uQlStNWE74Bip66jHDj2OgNSrscdA1agp7pSdVTRuXBEz0p2J3lFwiRuj35_8-fFT44SjXkWTVREtxsRuTWv2N9uFKsC42KCsgSXNtDeads7TYbbRTBZpugRJrZGaYUKt1o-ovvfYuwGjX9bHt6hs3C6_77Xrwwty1Ckb8OXDekK-frj4cv4xu7q-_HT-_iqDNZmsZFWlGccWADkDzatSFB2UVcoHaq6E1KKCFgoBUreiFq3EVgDmgIKBEOKEvDl4J---zxhiM5gAaK0a0c2h4Snzd0VeSJnQtwcUvAshBdpM3gzKLw1nzdpYkxpr9o0l9vWDdm4H1P_JfxUl4OwA3BmLy-Om5vO3m4PyL449qI4</recordid><startdate>201712</startdate><enddate>201712</enddate><creator>Haines, J. M.</creator><creator>Lee, P. M.</creator><creator>Hegedus, R. M.</creator><creator>Hwang, J. K.</creator><creator>Court, M. H.</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-6003-0496</orcidid><orcidid>https://orcid.org/0000-0002-8066-838X</orcidid></search><sort><creationdate>201712</creationdate><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</title><author>Haines, J. M. ; Lee, P. M. ; Hegedus, R. M. ; Hwang, J. K. ; Court, M. 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H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Establishment of reference ranges and evaluation of in vitro concentration‐dependent platelet inhibition by acetylsalicylic acid for multiple electrode impedance aggregometry in healthy dogs</atitle><jtitle>Journal of veterinary pharmacology and therapeutics</jtitle><addtitle>J Vet Pharmacol Ther</addtitle><date>2017-12</date><risdate>2017</risdate><volume>40</volume><issue>6</issue><spage>618</spage><epage>628</epage><pages>618-628</pages><issn>0140-7783</issn><eissn>1365-2885</eissn><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 Emax model 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.</abstract><cop>England</cop><pmid>28387027</pmid><doi>10.1111/jvp.12405</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-6003-0496</orcidid><orcidid>https://orcid.org/0000-0002-8066-838X</orcidid></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Animals Anti-Inflammatory Agents, Non-Steroidal - administration & dosage Anti-Inflammatory Agents, Non-Steroidal - pharmacology Aspirin - administration & dosage Aspirin - pharmacology Blood Platelets - drug effects Dogs Dose-Response Relationship, Drug Electric Impedance Female Male Platelet Aggregation - drug effects Reference Values |
| 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 |
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