Harm Tobias, Lahu Shqipdona, Mayer Katharina, Rath Dominik, Geisler Tobias, Müller Karin Anne Lydia, Janisch Marion, Adler Kristin, Münch Götz, Massberg Steffen, Kastrati Adnan, Gawaz Meinrad Paul
Department of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany.
Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen, Technische Universität München, Munich, Germany.
Clin Res Cardiol. 2025 May 21. doi: 10.1007/s00392-025-02675-8.
Patients with coronary artery disease (CAD) are at increased risk of developing ischemic events and contemporary antiplatelet therapy often leads to bleeding events following percutaneous coronary intervention (PCI). Glycoprotein VI (GPVI) is the key receptor of collagen-dependent thrombus formation and crucial for platelet homeostasis.
We analysed the influence of GPVI inhibition with revacept in a randomized double-blinded trial enrolling 334 patients with CAD undergoing elective PCI. Ex vivo platelet function analyses were assessed alongside plasma chemokine concentrations. We then elucidate changes of GPVI-dependent chemokine concentrations in patients with bleeding events during the 30-day clinical follow-up.
Changes in platelet function occur in patients with revacept treatment and are associated with a characteristic alteration of circulating chemokine concentrations. Further, patients with adverse bleeding events share a distinct fingerprint of chemokines that is associated with modulation of in vitro platelet functions. In addition, assessment of GPVI-associated changes in chemokine signalling and platelet functions demonstrated an increased diagnostic value in patients with CAD and might improve early risk discrimination for bleeding events.
The composition of platelet-derived chemokines correlated with platelet functions following antiplatelet treatment. Thus, assessment of chemokines may offer the perspective to identify patients at increased risk for bleeding events. Likewise, modulation of platelet chemokines in patients with revacept treatment contributes to the efficacy of antiplatelet treatment and might attenuate pathophysiological cascades leading to haemorrhagic diathesis in patients with CAD.
冠心病（CAD）患者发生缺血事件的风险增加，并且当代抗血小板治疗在经皮冠状动脉介入治疗（PCI）后常导致出血事件。糖蛋白VI（GPVI）是胶原依赖性血栓形成的关键受体，对血小板稳态至关重要。
我们在一项随机双盲试验中分析了Revacept抑制GPVI的影响，该试验纳入了334例接受择期PCI的CAD患者。体外血小板功能分析与血浆趋化因子浓度一同进行评估。然后我们阐明了在30天临床随访期间发生出血事件的患者中GPVI依赖性趋化因子浓度的变化。
接受Revacept治疗的患者血小板功能发生变化，并与循环趋化因子浓度的特征性改变相关。此外，发生不良出血事件的患者具有独特的趋化因子特征，这与体外血小板功能的调节相关。此外，对趋化因子信号传导和血小板功能中与GPVI相关的变化进行评估显示，对CAD患者具有更高的诊断价值，并且可能改善出血事件的早期风险辨别。
抗血小板治疗后血小板衍生趋化因子的组成与血小板功能相关。因此，评估趋化因子可能为识别出血事件风险增加的患者提供思路。同样，Revacept治疗患者中血小板趋化因子的调节有助于抗血小板治疗的疗效，并可能减弱导致CAD患者出血素质的病理生理级联反应。
