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