{"title":"Platelet Function Assay Using Dielectric Blood Coagulometry","authors":"Yoshihito Hayashi, Yudai Yamamoto, Aya Murata, Kenzo Machida, Yoichi Katsumoto, Tokujiro Uchida","doi":"10.1021/acs.analchem.4c04112","DOIUrl":null,"url":null,"abstract":"The hemostatic function of platelets is complementary to blood coagulation. However, traditional platelet function tests have primarily focused on measuring platelet aggregation, reducing their clinical effectiveness for antiplatelet drug monitoring. To address this limitation, we propose a new test principle that evaluates platelet function and the effects of antiplatelet drugs through blood coagulation reactions. This principle was validated in model experimental systems using blood samples from healthy volunteers (<i>n</i> = 11), where antiplatelet drugs such as aspirin, prostaglandin E1, or ticagrelor were added to the blood samples. Ticagrelor was tested at four concentration levels, covering the expected therapeutic range. We found that the complementary function of platelets can be assessed by monitoring the 1 MHz dielectric permittivity during the blood coagulation process, particularly the peak value. When reagents such as agonists (arachidonic acid, collagen, or adenosine diphosphate ADP) and calcium were mixed into the citrated blood with turbulence by pipetting, platelets became activated and aggregated before thrombin generation, resulting in a “consumed” state of platelets. Consequently, the contribution to the permittivity peak was minimal. By contrast, when blood spiked with antiplatelet drugs was tested, agonist-induced platelet aggregation was inhibited during the initial stage of the measurement. However, after thrombin generation, platelets were activated through the thrombin receptor. These activated platelets interacted with fibrin, thereby affecting the permittivity peak. The results of this validation process with Student’s <i>t</i>-tests confirm the fundamental operating principle of the proposed platelet function assay, thereby contributing to antiplatelet therapy monitoring.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"34 1","pages":""},"PeriodicalIF":6.7000,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Analytical Chemistry","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1021/acs.analchem.4c04112","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ANALYTICAL","Score":null,"Total":0}
引用次数: 0
Abstract
The hemostatic function of platelets is complementary to blood coagulation. However, traditional platelet function tests have primarily focused on measuring platelet aggregation, reducing their clinical effectiveness for antiplatelet drug monitoring. To address this limitation, we propose a new test principle that evaluates platelet function and the effects of antiplatelet drugs through blood coagulation reactions. This principle was validated in model experimental systems using blood samples from healthy volunteers (n = 11), where antiplatelet drugs such as aspirin, prostaglandin E1, or ticagrelor were added to the blood samples. Ticagrelor was tested at four concentration levels, covering the expected therapeutic range. We found that the complementary function of platelets can be assessed by monitoring the 1 MHz dielectric permittivity during the blood coagulation process, particularly the peak value. When reagents such as agonists (arachidonic acid, collagen, or adenosine diphosphate ADP) and calcium were mixed into the citrated blood with turbulence by pipetting, platelets became activated and aggregated before thrombin generation, resulting in a “consumed” state of platelets. Consequently, the contribution to the permittivity peak was minimal. By contrast, when blood spiked with antiplatelet drugs was tested, agonist-induced platelet aggregation was inhibited during the initial stage of the measurement. However, after thrombin generation, platelets were activated through the thrombin receptor. These activated platelets interacted with fibrin, thereby affecting the permittivity peak. The results of this validation process with Student’s t-tests confirm the fundamental operating principle of the proposed platelet function assay, thereby contributing to antiplatelet therapy monitoring.
期刊介绍:
Analytical Chemistry, a peer-reviewed research journal, focuses on disseminating new and original knowledge across all branches of analytical chemistry. Fundamental articles may explore general principles of chemical measurement science and need not directly address existing or potential analytical methodology. They can be entirely theoretical or report experimental results. Contributions may cover various phases of analytical operations, including sampling, bioanalysis, electrochemistry, mass spectrometry, microscale and nanoscale systems, environmental analysis, separations, spectroscopy, chemical reactions and selectivity, instrumentation, imaging, surface analysis, and data processing. Papers discussing known analytical methods should present a significant, original application of the method, a notable improvement, or results on an important analyte.