Hayashi Yoshihito, Yamamoto Yudai, Murata Aya, Machida Kenzo, Katsumoto Yoichi, Uchida Tokujiro
Biomedical R&D Department, R&D Division, Medical Business Group, Sony Imaging Products & Solutions Inc., Bunkyo-ku 113-8510, Tokyo, Japan.
Department of Anesthesiology, Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, 1-5-45 Yushima, Bunkyo-ku 113-8510, Tokyo, Japan.
Anal Chem. 2025 Feb 4;97(4):2036-2043. doi: 10.1021/acs.analchem.4c04112. Epub 2025 Jan 23.
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 ( = 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 -tests confirm the fundamental operating principle of the proposed platelet function assay, thereby contributing to antiplatelet therapy monitoring.
血小板的止血功能与血液凝固相辅相成。然而，传统的血小板功能测试主要侧重于测量血小板聚集，这降低了它们在抗血小板药物监测中的临床有效性。为解决这一局限性，我们提出了一种新的测试原理，即通过血液凝固反应来评估血小板功能和抗血小板药物的效果。这一原理在使用健康志愿者（n = 11）血液样本的模型实验系统中得到了验证，在这些血液样本中添加了阿司匹林、前列腺素E1或替格瑞洛等抗血小板药物。替格瑞洛在四个浓度水平上进行了测试，涵盖了预期的治疗范围。我们发现，血小板的互补功能可以通过监测血液凝固过程中的1 MHz介电常数来评估，特别是峰值。当通过移液管将激动剂（花生四烯酸、胶原蛋白或二磷酸腺苷ADP）和钙等试剂与枸橼酸盐血液湍流混合时，血小板在凝血酶生成之前被激活并聚集，导致血小板处于“消耗”状态。因此，对介电常数峰值的贡献最小。相比之下，当测试添加了抗血小板药物的血液时，在测量的初始阶段激动剂诱导的血小板聚集受到抑制。然而，在凝血酶生成后，血小板通过凝血酶受体被激活。这些激活的血小板与纤维蛋白相互作用，从而影响介电常数峰值。使用学生t检验的这一验证过程的结果证实了所提出的血小板功能测定的基本操作原理，从而有助于抗血小板治疗监测。
