Matsuda Masato, Shimomura Daiki, Suzuki Takeshi, Tabuchi Yuka, Kurono Hiroshi, Nishi Keisuke, Arai Nobuo, Hoshiyama Yoshiki, Kamioka Mikio, Moriyama Masato, Matsumoto Tomoko
Medical Laboratory Division, Niigata University Medical and Dental Hospital, 1-754, Asahimachi-dori, Chuo-ku, Niigata, 951-8520, Japan.
Department of Clinical Laboratory Sciences, School of Health Sciences, Fukushima Medical University, 10-6, Sakae-machi, Fukushima, 960-8516, Japan.
Sci Rep. 2025 Sep 2;15(1):32336. doi: 10.1038/s41598-025-15089-3.
Activated partial thromboplastin time (APTT) prolongation occurs due to coagulation factor deficiencies/inhibitors, lupus anticoagulant (LA), and anticoagulant-taking, necessitating discrimination through further testing. Clot waveform analysis (CWA) can discriminate causes while measuring APTT, but conventional CWA exhibits moderate accuracy due to visual judgement and limited parameter use. We applied deep learning (DL) techniques to huge numerical data constituting clot waveforms and their first- and second-derivative curves (CWA curves) to leverage hidden features for developing an accurate classification model. We utilized a multi-wavelength detection system embedded in modern coagulometers to obtain multi-wavelength CWA curves. A convolutional neural network-based DL model was trained on 683 samples (135 hemophilic, 95 LA-positive, 99 heparin-treated, 105 warfarin-treated, and 249 direct oral anticoagulant-treated) and evaluated using 10-fold cross-validation. Conventional CWA parameters showed limited discrimination abilities (area under the curve [AUC] 0.532-0.858). DL models using single-wavelength CWA curves achieved higher performance (AUC 0.943-0.988), and multi-wavelength CWA curves further improved it (AUC 0.961-0.993) with high sensitivity (≥ 88.0%), specificity (> 92.0%), and overall accuracy (88.4%), although the performance may depend on reagents and/or analyzers. DL models using multi-wavelength CWA curves show promise as high-performance screening tools for classifying APTT prolongation causes and are best built in each laboratory.
活化部分凝血活酶时间(APTT)延长是由于凝血因子缺乏/抑制剂、狼疮抗凝物(LA)以及服用抗凝剂所致,因此需要通过进一步检测来鉴别。凝块波形分析(CWA)在测量APTT的同时可以鉴别病因,但传统的CWA由于视觉判断和参数使用有限,准确性一般。我们将深度学习(DL)技术应用于构成凝块波形及其一阶和二阶导数曲线(CWA曲线)的大量数值数据,以利用隐藏特征来开发准确的分类模型。我们利用现代凝血仪中嵌入的多波长检测系统来获取多波长CWA曲线。基于卷积神经网络的DL模型在683个样本(135个血友病患者、95个LA阳性、99个接受肝素治疗、105个接受华法林治疗以及249个接受直接口服抗凝剂治疗)上进行训练,并使用10折交叉验证进行评估。传统的CWA参数显示出有限的鉴别能力(曲线下面积[AUC]为0.532 - 0.858)。使用单波长CWA曲线的DL模型具有更高的性能(AUC为0.943 - 0.988),而多波长CWA曲线进一步提升了性能(AUC为0.961 - 0.993),具有高灵敏度(≥88.0%)、高特异性(>92.0%)和总体准确性(88.4%),尽管性能可能取决于试剂和/或分析仪。使用多波长CWA曲线的DL模型有望成为用于分类APTT延长病因的高性能筛查工具,并且最好在每个实验室构建。