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深静脉血栓形成的新型诊断生物标志物的鉴定。

Identification of novel diagnostic biomarkers for deep venous thrombosis.

机构信息

Centre for Primary Health Care Research, Department of Clinical Sciences, Lund University/Skåne University Hospital, Malmö, Sweden.

Department of Family Medicine and Community Health, Department of Population Health Science and Policy Icahn School of Medicine at Mount Sinai, New York, NY, USA.

出版信息

Br J Haematol. 2018 May;181(3):378-385. doi: 10.1111/bjh.15206. Epub 2018 Apr 19.

Abstract

The combination of a negative D-dimer and a Wells score can rule out, but not confirm, a diagnosis of deep venous thrombosis (DVT). We aimed to identify new diagnostic biomarkers for DVT and to investigate their relationship with hypercoagulability markers [D-dimer and activated protein C-protein C inhibitor (APC-PCI) complex]. We screened 92 cardiovascular-specific proteins in plasma samples from 45 confirmed DVT patients and 45 age- and sex-matched non-DVT patients selected from a prospective multicentre diagnostic management study (SCORE) by Proseek Multiplex CVDIII . Plasma levels of 30 proteins were significantly different between DVT and non-DVT patients. After Bonferroni correction, plasma levels of seven proteins: P-selectin, transferrin receptor protein 1, von Willebrand factor, tissue factor pathway inhibitor, osteopontin (OPN), bleomycin hydrolase and ST2 protein remained significantly different. The area under curve (AUC) for these proteins ranged from 0·70 to 0·84. Furthermore, all seven identified proteins were significantly associated with markers of hypercoagulability. A combination of OPN and APC-PCI had the best ability to discriminate DVT from non-DVT patients (AUC = 0·94; sensitivity = 89% and specificity = s84%). In conclusion, we identified multiple proteins associated with markers of hypercoagulability and with a potential to become novel diagnostic biomarkers for DVT.

摘要

阴性 D-二聚体和 Wells 评分的联合可排除深静脉血栓形成(DVT)的诊断,但不能确诊。我们旨在寻找新的 DVT 诊断生物标志物,并研究其与高凝标志物[D-二聚体和活化蛋白 C-蛋白 C 抑制剂(APC-PCI)复合物]的关系。我们通过 Proseek Multiplex CVDIII 在一项前瞻性多中心诊断管理研究(SCORE)中筛选了 45 例确诊 DVT 患者和 45 例年龄和性别匹配的非 DVT 患者的血浆样本中的 92 种心血管特异性蛋白。DVT 和非 DVT 患者的血浆中 30 种蛋白质水平存在显著差异。经过 Bonferroni 校正后,有 7 种蛋白质(P-选择素、转铁蛋白受体蛋白 1、血管性血友病因子、组织因子途径抑制剂、骨桥蛋白、博来霉素水解酶和 ST2 蛋白)的血浆水平仍存在显著差异。这些蛋白质的 AUC 范围为 0.70 至 0.84。此外,所有 7 种鉴定出的蛋白质均与高凝标志物显著相关。OPN 和 APC-PCI 的组合对区分 DVT 和非 DVT 患者的能力最佳(AUC=0.94;敏感性为 89%,特异性为 84%)。总之,我们发现了多种与高凝标志物相关且可能成为 DVT 新的诊断生物标志物的蛋白质。

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