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比较检测肝素结合部位抗凝血酶缺陷症患者的抗凝血酶活性检测方法:系统评价和荟萃分析。

Comparison of antithrombin activity assays in detection of patients with heparin binding site antithrombin deficiency: systematic review and meta-analysis.

机构信息

Laboratory for Haemostasis and Atherothrombosis, Department of Vascular Diseases, University Medical Centre Ljubljana, 1000, Ljubljana, Slovenia.

Faculty of Pharmacy, University of Ljubljana, 1000, Ljubljana, Slovenia.

出版信息

Sci Rep. 2023 Oct 4;13(1):16734. doi: 10.1038/s41598-023-43941-x.

DOI:10.1038/s41598-023-43941-x
PMID:37794095
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10551003/
Abstract

Antithrombin (AT) deficiency increases the risk for venous thromboembolism, therefore, a highly sensitive assay to identify this condition is crucial. The aim of this paper was to perform a meta-analysis comparing AT activities measured by different AT activity assays in patients with heparin binding site AT deficiency. In addition, the diagnostic sensitivity of selected assays was compared depending on the available data. An extensive literature search was performed considering results with publication date up to July 10, 2021. Seven relevant English-language observational studies, comparing AT activity measured by different AT activity assays in Caucasian Europeans with either the AT Budapest III or AT Padua I mutation were included in meta-analyses. There was no significant difference in AT activity between Labexpert and Innovance in patients with AT Budapest III (P = 0.567) and AT Padua I (P = 0.265), while AT activity determined by HemosIL was significantly higher compared to Innovance for both mutations (AT Budapest III: P < 0.001; AT Padua I: P < 0.001). These results are in line with the results of comparison of diagnostic sensitivity. In patients with AT Budapest III, the AT activity was also higher when measured with Berichrom compared to Innovance (P = 0.002), however, the results of comparison of diagnostic sensitivity across studies were variable. No significant difference (P = 0.117) in AT activity as well as diagnostic sensitivity was observed between Sta-Stachrom and Innovance. The results of our study suggest that Innovance, Labexpert and Sta-Stachrom are the most sensitive activity assays for detection of AT Budapest III and AT Padua I, whereas HemosIL showed considerably lower sensitivity for these two variants. As revealed in our study, the diagnostic sensitivity of AT activity assays to type II heparin binding site AT deficiency is different, and in some assays mutation dependent.

摘要

抗凝血酶 (AT) 缺乏会增加静脉血栓栓塞的风险,因此,识别这种情况的高敏感检测方法至关重要。本文的目的是进行一项荟萃分析,比较不同 AT 活性测定方法在肝素结合位点 AT 缺乏症患者中的 AT 活性。此外,根据现有数据比较了选定检测方法的诊断灵敏度。考虑到截至 2021 年 7 月 10 日的研究结果,进行了广泛的文献检索。有 7 项相关的英语观察性研究,比较了白种欧洲人 AT 布达佩斯 III 或 AT 帕多瓦 I 突变患者中不同 AT 活性测定方法的 AT 活性,被纳入荟萃分析。在 AT 布达佩斯 III(P=0.567)和 AT 帕多瓦 I(P=0.265)患者中,Labexpert 和 Innovance 之间的 AT 活性无显著差异,而 HemosIL 测定的 AT 活性明显高于两种突变的 Innovance(AT 布达佩斯 III:P<0.001;AT 帕多瓦 I:P<0.001)。这些结果与诊断灵敏度比较的结果一致。在 AT 布达佩斯 III 患者中,与 Innovance 相比,Berichrom 测量的 AT 活性也更高(P=0.002),然而,各研究之间的诊断灵敏度比较结果不一致。Sta-Stachrom 和 Innovance 之间的 AT 活性(P=0.117)以及诊断灵敏度均无显著差异。我们的研究结果表明,Innovance、Labexpert 和 Sta-Stachrom 是检测 AT 布达佩斯 III 和 AT 帕多瓦 I 的最敏感的活性检测方法,而 HemosIL 对这两种变体的敏感性较低。正如我们的研究表明,AT 活性检测方法对 II 型肝素结合位点 AT 缺乏症的诊断灵敏度不同,且在某些检测方法中依赖于突变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8b3/10551003/7815620df324/41598_2023_43941_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8b3/10551003/1c5125235ecf/41598_2023_43941_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8b3/10551003/66e75371849c/41598_2023_43941_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8b3/10551003/7815620df324/41598_2023_43941_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8b3/10551003/1c5125235ecf/41598_2023_43941_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8b3/10551003/66e75371849c/41598_2023_43941_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8b3/10551003/7815620df324/41598_2023_43941_Fig4_HTML.jpg

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Functional Characterization of Antithrombin Mutations by Monitoring of Thrombin Inhibition Kinetics.通过监测凝血酶抑制动力学对抗凝血酶突变进行功能表征。
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