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活化部分凝血活酶时间(APTT)试剂成分的差异会影响凝血波形分析。

Differences in the Composition of Activated Partial Thromboplastin Time (APTT) Reagents Affect Clot Waveform Analysis.

作者信息

Kato Konami, Hatayama Yuki, Shimohiro Hisashi, Ichikawa Hitomi, Fukuda Tetsuya

机构信息

Division of Clinical Laboratory, Tottori University Hospital, Yonago 683-8504, Japan and.

Department of Pathobiological Science and Technology, School of Health Sciences, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan.

出版信息

Yonago Acta Med. 2022 Aug 29;65(3):226-230. doi: 10.33160/yam.2022.08.013. eCollection 2022 Aug.

DOI:10.33160/yam.2022.08.013
PMID:36061578
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9419218/
Abstract

BACKGROUND

Clot waveform analysis (CWA) based on activated partial thromboplastin time (APTT) is a useful assay for hemostasis. However, the effects of activators and phospholipid conditions on CWA have not been adequately investigated. Therefore, we characterized CWA using four different APTT reagents.

METHODS

We used 39 archived plasma samples from patients with hemophilia A (HA), 16 samples from patients with HA under emicizumab treatment, and 10 samples from healthy individuals for CWA with four different types of APTT reagents (reagents A, B, C, and D). We then compared Ad|min1|, Ad|min2|, and Ad|max2| from the CWA, which reflect the maximum velocity, maximum acceleration, and maximum deceleration, respectively, among the four reagents.

RESULTS

Similar clot waveform shapes were observed for each reagent in the healthy donor group, HA group, and HA under emicizumab group, and the waveform was different for each target group. Significant changes were found in clotting time (CT) (s), Ad|min1| (%/s), Ad|min2| (%/s), and Ad|max2| (%/s). The waveform pattern for the coagulation reaction by reagent D, comprising silica and synthetic phospholipids, was the fastest among the reagents examined. Further, the difference in Ad|min1| (%/s) and Ad|min2| (%/s) was larger than that in CT depending on the reagent used(s), indicating that the measured value of CWA was affected by the reagent composition.

CONCLUSION

Our results showed a significant difference among reagents with varying composition and concentration; this was found to affect the parameters obtained from CWA. Thus, the differences between reagents hinder standardization of quantitative evaluation using these parameters; further, this highlights the necessity of understanding the characteristics of APTT reagents and determining the reference range in individual facilities.

摘要

背景

基于活化部分凝血活酶时间(APTT)的凝血块波形分析(CWA)是一种用于止血的有用检测方法。然而,激活剂和磷脂条件对CWA的影响尚未得到充分研究。因此,我们使用四种不同的APTT试剂对CWA进行了表征。

方法

我们使用了39份来自A型血友病(HA)患者的存档血浆样本、16份接受emicizumab治疗的HA患者样本以及10份来自健康个体的样本,用四种不同类型的APTT试剂(试剂A、B、C和D)进行CWA检测。然后,我们比较了CWA中的Ad|min1|、Ad|min2|和Ad|max2|,它们分别反映了四种试剂中的最大速度、最大加速度和最大减速度。

结果

在健康供体组、HA组和emicizumab治疗的HA组中,每种试剂观察到相似的凝血块波形形状,并且每个目标组的波形不同。在凝血时间(CT)(秒)、Ad|min1|(%/秒)、Ad|min2|(%/秒)和Ad|max2|(%/秒)方面发现了显著变化。包含二氧化硅和合成磷脂的试剂D的凝血反应波形模式在所检测的试剂中是最快的。此外,根据所使用的试剂,Ad|min1|(%/秒)和Ad|min2|(%/秒)的差异大于CT的差异,表明CWA的测量值受试剂组成的影响。

结论

我们的结果显示不同组成和浓度的试剂之间存在显著差异;发现这会影响从CWA获得的参数。因此,试剂之间的差异阻碍了使用这些参数进行定量评估的标准化;此外,这突出了了解APTT试剂特性并在各个机构确定参考范围的必要性。

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本文引用的文献

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A correlation of thrombin generation assay and clot waveform analysis in patients on warfarin.华法林治疗患者凝血酶生成试验与血栓弹力图分析的相关性。
Hematology. 2022 Dec;27(1):337-342. doi: 10.1080/16078454.2022.2043573.
2
Regression Analysis to Estimate the Factor VIII Activity of Patients with Hemophilia A Without Inhibitor who Received Emicizumab Therapy.回归分析估计接受艾美赛珠单抗治疗的无抑制剂血友病 A 患者的因子 VIII 活性。
Clin Appl Thromb Hemost. 2022 Jan-Dec;28:10760296221082992. doi: 10.1177/10760296221082992.
3
Clot waveform of APTT has abnormal patterns in subjects with COVID-19.COVID-19 患者的 APTT 凝血波形出现异常模式。
Sci Rep. 2021 Mar 4;11(1):5190. doi: 10.1038/s41598-021-84776-8.
4
Update on the Clot Waveform Analysis.血栓波形分析进展。
Clin Appl Thromb Hemost. 2020 Jan-Dec;26:1076029620912027. doi: 10.1177/1076029620912027.
5
Assessment of aPTT-based clot waveform analysis for the detection of haemostatic changes in different types of infections.基于 aPTT 的血栓波形分析评估不同类型感染中的止血变化。
Sci Rep. 2020 Aug 25;10(1):14186. doi: 10.1038/s41598-020-71063-1.
6
Prediction of the haemostatic effects of bypassing therapy using comprehensive coagulation assays in emicizumab prophylaxis-treated haemophilia A patients with inhibitors.在接受依库珠单抗预防治疗的有抑制剂的血友病 A 患者中,使用综合凝血检测预测旁路治疗的止血效果。
Br J Haematol. 2020 Sep;190(5):727-735. doi: 10.1111/bjh.16574. Epub 2020 Mar 12.
7
Laboratory testing in hemophilia: Impact of factor and non-factor replacement therapy on coagulation assays.血友病的实验室检测:凝血因子和非凝血因子替代疗法对凝血检测的影响。
J Thromb Haemost. 2020 Jun;18(6):1242-1255. doi: 10.1111/jth.14784. Epub 2020 Apr 23.
8
Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.异常的凝血参数与新型冠状病毒肺炎患者的预后不良有关。
J Thromb Haemost. 2020 Apr;18(4):844-847. doi: 10.1111/jth.14768. Epub 2020 Mar 13.
9
Modified clot waveform analysis to measure plasma coagulation potential in the presence of the anti-factor IXa/factor X bispecific antibody emicizumab.改良血栓波形分析在抗因子 IXa/因子 X 双特异性抗体emicizumab 存在的情况下测量血浆凝血潜能。
J Thromb Haemost. 2018 Jun;16(6):1078-1088. doi: 10.1111/jth.14022. Epub 2018 May 13.
10
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Clin Appl Thromb Hemost. 2018 Jul;24(5):764-770. doi: 10.1177/1076029617724230. Epub 2017 Sep 8.