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微粒体表达的组织因子与癌症患者的死亡率相关,但与血栓形成无关。

Tissue factor expressed by microparticles is associated with mortality but not with thrombosis in cancer patients.

机构信息

José A. Páramo, Servicio de Hematología, Clínica Universidad de Navarra, Av. Pio XII, 36, 31008 Pamplona, Navarra, Spain, Tel.: +34 948 296397, Fax: +34 948 296500, E-mail:

出版信息

Thromb Haemost. 2013 Sep;110(3):598-608. doi: 10.1160/TH13-02-0122. Epub 2013 Jun 27.

Abstract

A prothrombotic state is one of the hallmarks of malignancy and a major contributor to morbidity and mortality in cancer patients.Tissue factor (TF) is often overexpressed in malignancy and is a prime candidate in predicting the hypercoagulable state. Moreover, increased number of TF-exposing microparticles (MPs) in cancer patients may contribute to venous thromboembolism (VTE). We have conducted a prospective cohort study to determine whether elevated TF antigen, TF activity and TF associated to MPs (MPs-TF) are predictive of VTE and mortality in cancer patients. The studied population consisted of 252 cancer patients and 36 healthy controls. TF antigen and activity and MPs-TF were determined by ELISA and chromogenic assays. During a median follow-up of 10 months, 40 thrombotic events were recorded in 34 patients (13.5%), and 73 patients (28.9%) died. TF antigen and activity were significantly higher in patients than in controls (p<0.01) mainly in patients with advanced stages, whereas no differences were observed for TF activity of isolated MPs. We did not find a statistically significant association of TF variables with the risk of VTE. Multivariate analysis adjusting for age, sex, type of cancer and other confounding variables showed that TF activity (p<0.01) and MPs-TF activity (p<0.05) were independently associated with mortality. In conclusion, while TF variables were not associated with future VTE in cancer patients, we found a strong association of TF and MPs-TF activity with mortality, thus suggesting they might be good prognostic markers in cancer patients.

摘要

促血栓状态是恶性肿瘤的特征之一,也是癌症患者发病率和死亡率的主要原因。组织因子 (TF) 在恶性肿瘤中常过度表达,是预测高凝状态的主要候选物。此外,癌症患者中 TF 暴露的微颗粒 (MPs) 数量增加可能导致静脉血栓栓塞症 (VTE)。我们进行了一项前瞻性队列研究,以确定 TF 抗原、TF 活性和与 MPs 相关的 TF (MPs-TF) 是否可预测癌症患者的 VTE 和死亡率。研究人群包括 252 例癌症患者和 36 名健康对照者。通过 ELISA 和显色测定法测定 TF 抗原和活性以及 MPs-TF。在中位数为 10 个月的随访期间,34 例患者(13.5%)记录到 40 例血栓事件,73 例患者(28.9%)死亡。患者的 TF 抗原和活性明显高于对照组(p<0.01),主要是在晚期患者中,而孤立 MPs 的 TF 活性没有差异。我们没有发现 TF 变量与 VTE 风险之间存在统计学显著关联。调整年龄、性别、癌症类型和其他混杂变量的多变量分析显示,TF 活性(p<0.01)和 MPs-TF 活性(p<0.05)与死亡率独立相关。总之,虽然 TF 变量与癌症患者未来的 VTE 无关,但我们发现 TF 和 MPs-TF 活性与死亡率有很强的关联,因此提示它们可能是癌症患者的良好预后标志物。

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