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老年髋部骨折患者应用肝素治疗后的炎症生物标志物谱分析。

Inflammatory biomarker profiling in elderly patients with acute hip fracture treated with heparins.

机构信息

Loyola Universtity Stritch School of Medicine Maywood, Illinois 60153, USA.

出版信息

Clin Appl Thromb Hemost. 2010 Feb;16(1):42-50. doi: 10.1177/1076029609351876. Epub 2009 Dec 2.

Abstract

Hip fracture is common in the elderly patients with associated high risk of venous thromboembolic complications. Pathogenic activation results in the generation of various surrogate markers in plasma. This study is designed to identify unique biomarkers in elderly patients with hip fracture using protein chip array enzyme-linked immunosorbent assay (ELISA) methods. Plasma from a randomized hip fracture study (PK-532; n = 341) treated with either enoxaparin (40 mg once daily) or unfractionated heparin (UFH; 5000 IU twice daily) were collected prior to and at 1, 3, 5, and 7 days. A total of 52 samples were analyzed using proteomic surface-enhanced laser desorption/ ionization-time of flight (SELDI-TOF) mass spectrometry to identify unique biomarkers in the molecular weight range of 0 to 150 kd. Twenty-nine healthy volunteer's and pooled plasma from total hip replacement/total knee replacement patients with a unique biomarker at 11.9 kd were used as quality controls. In the 29 healthy individuals, the biomarker profile did not reveal the presence of any unique peak in comparison to the reference normal human plasma (NHP). Plasma obtained prior to surgery exhibits unique biomarkers in 4 of 52 (7.6%) of the samples. On day 1 postoperatively, 41 of 51 (80.3%) showed a distinct peak at 11.9 kd. On day 3, 43 of 49 (87.8%) patients showed the presence of this biomarker most often at its strongest intensity. In all, 22 of 44 (50%) showed this biomarker on day 5 and 4 of 23 (17.9%) on day 7. C-reactive protein (CRP), tumor necrosis factor alpha (TNF-alpha), and serum amyloid A were also increased after surgery. Tissue factor pathway inhibitor (TFPI) antigen levels were increased due to the treatment modalities.

摘要

髋部骨折在老年患者中很常见,且伴有静脉血栓栓塞并发症的高风险。致病激活导致血浆中产生各种替代标志物。本研究旨在使用蛋白质芯片阵列酶联免疫吸附测定(ELISA)方法鉴定老年髋部骨折患者的独特生物标志物。从接受依诺肝素(40 mg 每日一次)或未分级肝素(UFH;5000 IU 每日两次)治疗的随机髋部骨折研究(PK-532;n=341)中采集血浆,分别在治疗前和第 1、3、5 和 7 天采集。使用蛋白质组学表面增强激光解吸/电离飞行时间(SELDI-TOF)质谱分析总共 52 个样本,以鉴定分子量在 0 至 150 kd 范围内的独特生物标志物。29 名健康志愿者和来自全髋关节置换/全膝关节置换患者的合并血浆,其中 11.9 kd 处有独特的生物标志物,作为质量控制。在 29 名健康个体中,与参考正常人类血浆(NHP)相比,生物标志物谱未显示存在任何独特峰。手术前获得的血浆在 4/52(7.6%)样本中显示出独特的生物标志物。术后第 1 天,51 例中有 41 例(80.3%)在 11.9 kd 处显示出明显的峰值。第 3 天,49 例中有 43 例(87.8%)患者最常以最强强度显示出该生物标志物。在所有患者中,22 例在第 5 天和 4 例在第 7 天显示出该生物标志物。术后 C 反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)和血清淀粉样蛋白 A 也增加。组织因子途径抑制剂(TFPI)抗原水平因治疗方式而增加。

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