AbstractActivated partial thromboplastin time (aPTT)-based clot waveform analysis (CWA) is a plasma-based global haemostatic assay. Elevated CWA parameters have been associated with hypercoagulability in venous thromboembolism, but its role in arterial thrombotic disease is uncertain. This study aims to explore the relationship between aPTT-based CWA and acute myocardial infarction (AMI) and its complications.

摘要基于活化部分凝血活酶时间（aPTT）的凝块波形分析（CWA）是一种基于血浆的全局止血测定。CWA参数升高与静脉血栓栓塞症的高凝状态有关，但其在动脉血栓性疾病中的作用尚不确定。本研究旨在探讨基于aPTT的CWA与急性心肌梗死（AMI）及其并发症之间的关系。

In a retrospective cohort study of patients with AMI who underwent emergency cardiac catheterisation, pre-procedural aPTT and CWA parameters—min1, min2 and max2 were measured. These were compared against a control group of patients, consisting of patients who underwent elective orthopaedic and urological procedures.

在一项对接受紧急心脏导管插入术的AMI患者进行的回顾性队列研究中，测量了术前aPTT和CWA参数min1，min2和max2。将这些患者与对照组患者进行比较，对照组患者由接受选择性骨科和泌尿外科手术的患者组成。

Within the AMI cohort, we also compared aPTT and CWA parameters of those with and without clinical complications of AMI. Results: Compared to controls (N = 109), patients with AMI (N = 214) had shorter aPTT (26.7 ± 3.3 s vs 27.9 ± 1.7 s, P < 0.001) and higher CWA parameters (min1: 6.11 ± 1.40%/s vs 5.58 ± 1.14%/s; min2: 0.98 ± 0.23%/s2 vs 0.90 ± 0.19%/s2; max2: 0.81 ± 0.20%/s2 vs 0.74 ± 0.16%/s2, all P ≤ 0.001).

。结果：与对照组（N=109）相比，AMI患者（N=214）aPTT较短（26.7±3.3 s vs 27.9±1.7 s，P<0.001），CWA参数较高（min1:6.11±1.40%s vs 5.58±1.14%s；min2:0.98±0.23%/s2比0.90±0.19%/s2；最大值2:0.81±0.20%/s2比0.74±0.16%/s2，均P≤0.001）。

There was an increased incidence of elevated CWA parameters, in the AMI group, with odds ratio (OR) of 2.06 [95% CI 1.10–3.86], 2.23 (95% CI 1.18–4.24) and 2.01 (95% CI 1.07–3.77) for min1, min2 and max2, respectively. Similarly, elevated min1 and min2 were both individually associated with the presence of adverse outcomes of AMI, both with ORs of 2.63 (95% CI 1.24–5.59).

AMI组CWA参数升高的发生率增加，min1，min2和max2的比值比（OR）分别为2.06[95%CI 1.10-3.86]，2.23（95%CI 1.18-4.24）和2.01（95%CI 1.07-3.77）。同样，min1和min2升高均与AMI不良结局的存在单独相关，OR均为2.63（95%CI为1.24-5.59）。

Elevated aPTT-based CWA parameters are significantly associated with the occurrence of AMI and its complications. These findings identify the potential utility of CWA as risk and prognostic markers for AMI and warrants future works..

基于aPTT的CWA参数升高与AMI及其并发症的发生显着相关。这些发现确定了CWA作为AMI风险和预后标志物的潜在效用，并保证了未来的工作。。

IntroductionIschemic heart disease (IHD) is a major cause of morbidity and mortality worldwide1. The pathophysiology of acute myocardial infarction (AMI) is complex and involves multiple contributing factors as identified in Virchow’s triad2. While the procoagulant effect of platelets is an established feature in the pathogenesis of arterial thrombosis3, there has also been strong evidence for the contribution of heightened plasma coagulation pathway activity.

引言缺血性心脏病（IHD）是全球发病率和死亡率的主要原因1。急性心肌梗死（AMI）的病理生理学很复杂，涉及Virchow triad2中确定的多种因素。虽然血小板的促凝血作用是动脉血栓形成发病机制中的既定特征3，但也有强有力的证据表明血浆凝血途径活性升高。

High compositions of fibrin in arterial thrombi4, raised levels of tissue factor5, fibrinogen6,7, and intrinsic clotting factors VIII and IX8,9, as well as positive associations with clotting factor genetic variations Factor V Leiden and prothrombin 20210A10 have been demonstrated in patients with IHD.

IHD患者已证实动脉血栓中纤维蛋白的高组成4，组织因子5，纤维蛋白原6,7和内在凝血因子VIII和IX8,9水平升高，以及与凝血因子遗传变异因子V Leiden和凝血酶原20210A10呈正相关。

Global haemostatic assays, such as thrombin generation assay and viscoelastography, have the potential to evaluate the aggregated effects of different clotting factors and other plasmatic components, and emerging data also advocates for their potential utility in assessing the thrombotic risk in IHD11,12,13,14.Clot waveform analysis (CWA) is a global haemostatic assay, which evaluates the kinetics of fibrin clot formation during routine coagulation tests such as activated partial thromboplastin time (aPTT).

全球止血测定，如凝血酶生成测定和粘弹性成像，有可能评估不同凝血因子和其他血浆成分的聚集效应，新出现的数据也支持它们在评估IHD11,12,13,14中血栓形成风险方面的潜在效用。凝血酶波形分析（CWA）是一种全球止血测定，可评估常规凝血试验（如活化部分凝血活酶时间（aPTT））中纤维蛋白凝块形成的动力学。

Briefly, during the aPTT test, an optical analyser detects the clotting of blood, and the change in light transmittance or absorbance over time is plotted into a waveform for further derivation of kinetic parameters. There is substantial literature on the application of CWA in the diagnosis of and prognostication in haemophilia15,16, disseminated intravascular coagulation17,18 and sepsis19,20.

简而言之，在aPTT测试期间，光学分析仪检测血液凝固，并将透光率或吸光度随时间的变化绘制成波形，以进一步推导动力学参数。关于CWA在血友病15,16，弥散性血管内凝血17,18和败血症19,20的诊断和预后中的应用有大量文献。

CWA has also been used to demonstrate and characterise the hypercoagulability in venous thromboembolism21,22 and COVID-19.

CWA也被用于证明和表征静脉血栓栓塞21,22和COVID-19的高凝状态。

Data availability

数据可用性

The clinical data used in the current study are available in the Singapore Cardiac Data Bank (SCDB). The datasets generated during and/or analysed during the study are available from the corresponding author on reasonable request.

当前研究中使用的临床数据可在新加坡心脏数据库（SCDB）中获得。研究期间产生和/或分析的数据集可根据合理要求从通讯作者处获得。

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Download referencesAuthor informationAuthor notesThese authors contributed equally: Chen Lin Ng and Felix Maverick Uy.Authors and AffiliationsLee Kong Chian School of Medicine, Nanyang Technological University, Singapore, SingaporeChen Lin NgDepartment of Cardiology, National Heart Centre Singapore, Singapore, SingaporeFelix Maverick Uy, Yee How Lau & Khung Keong YeoDepartment of Haematology, Singapore General Hospital, Singapore, SingaporeMay Anne Cheong, Wan Hui Wong, Heng Joo Ng & Chuen Wen TanDuke-NUS Medical School, Singapore, SingaporeHeng Joo Ng, Khung Keong Yeo & Chuen Wen TanAuthorsChen Lin NgView author publicationsYou can also search for this author in.

下载参考文献作者信息作者注意到这些作者做出了同样的贡献：Chen Lin Ng和Felix Maverick Uy。作者和附属机构新加坡南洋理工大学医学院，新加坡Chen Lin Ng新加坡国家心脏中心心脏病学系，新加坡Felix Maverick Uy，Yee How Lau＆Khung Keong YeoDepartment of Haemology，Singapore General Hospital，Singapore，Anne Cheong，Wan Hui Wong，Heng Joo Ng＆Chuen Wen TanDuke NUS Medical School，Singapore，Heng Joo Ng，Khung Keong Yeo＆Chuen Wen Tan作者Chen NgView出版物您也可以在中搜索此作者。

PubMed Google ScholarFelix Maverick UyView author publicationsYou can also search for this author in

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PubMed Google ScholarMay Anne CheongView author publicationsYou can also search for this author in

PubMed Google ScholarMay Anne CheongView作者出版物您也可以在

PubMed Google ScholarWan Hui WongView author publicationsYou can also search for this author in

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PubMed Google ScholarYee How LauView author publicationsYou can also search for this author in

PubMed Google ScholarYee How LauView author Publications您也可以在

PubMed Google ScholarHeng Joo NgView author publicationsYou can also search for this author in

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PubMed Google ScholarKhung Keong YeoView author publicationsYou can also search for this author in

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PubMed Google ScholarContributionsN.C.L. and U.F.M. both participated in planning of study design, collected clinical data, performed statistical analysis, wrote the manuscript, along with the tables and figures. C.M.A. and W.W.H. assisted with collection of C.W.A. data, and reviewed the manuscript.

PubMed谷歌学术贡献。C、 L.和U.F.M.都参与了研究设计的规划，收集了临床数据，进行了统计分析，撰写了手稿以及表格和数字。C、 M.A.和W.W.H.协助收集了C.W.A.的数据，并审阅了手稿。

L.Y.H. contributed to clinical data collection and statistical analysis and reviewed the manuscript. N.H.J. participated in the study design, and reviewed and edited the manuscript. Y.K.K. participated in the study design, and reviewed and edited the manuscript. T.C.W. planned study design, oversaw clinical data and C.W.A.

五十、 Y.H.为临床数据收集和统计分析做出了贡献，并审阅了手稿。N、 H.J.参与了研究设计，并审查和编辑了手稿。Y、 K.K.参与了研究设计，并审查和编辑了手稿。T、 C.W.计划研究设计，监督临床数据和C.W.A。

data collection. He also oversaw statistical analysis, and reviewed and edited the final manuscript.Corresponding authorCorrespondence to.

数据收集。他还监督统计分析，并审查和编辑了最终手稿。对应作者对应。

Chuen Wen Tan.Ethics declarations

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Reprints and permissionsAbout this articleCite this articleNg, C.L., Uy, F.M., Cheong, M.A. et al. Activated partial thromboplastin time-based clot waveform analysis: a potential for application in acute myocardial infarction and its complications.

转载和许可本文引用本文Eng，C.L.，Uy，F.M.，Cheong，M.A。等人。基于活化部分凝血活酶时间的凝块波形分析：在急性心肌梗死及其并发症中的应用潜力。

Sci Rep 14, 20917 (2024). https://doi.org/10.1038/s41598-024-60098-3Download citationReceived: 31 July 2023Accepted: 18 April 2024Published: 09 September 2024DOI: https://doi.org/10.1038/s41598-024-60098-3Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

科学报告1420917（2024）。https://doi.org/10.1038/s41598-024-60098-3Download引文接收日期：2023年7月31日接收日期：2024年4月18日发布日期：2024年9月9日OI：https://doi.org/10.1038/s41598-024-60098-3Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

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