非小细胞肺癌患者凝血功能异常的相关因素与预后分析 Translated title: Analysis of the Factors Associated with Abnormal Coagulation and Prognosis in Patients with Non-small Cell Lung Cancer

Abstract

背景与目的

凝血及纤溶系统激活在肺癌患者中较为常见，与肺癌侵袭、转移的高风险和预后差相关。非小细胞肺癌（non-small cell lung cancer, NSCLC）占肺癌的80%-85%，本研究旨在回顾性分析凝血功能指标对NSCLC的预后价值，为目前NSCLC患者高凝状态的预防及治疗提供参考。

方法

回顾性分析2009年1月-2012年12月首次就诊于河北医科大学第四医院的604例经病理学证实的NSCLC患者的临床资料。资料内容包括患者治疗前凝血功能相关指标[血浆凝血酶原时间（prothrombin time, PT）、凝血酶原活动度（prothrombin time activity, PTA）、国际标准化比率（international normalized ratio, INR）、活化部分凝血活酶时间（activated partial thromboplastin time, APTT）、纤维蛋白原（fibrinogen, Fib）、D二聚体（D-dimer, D-D）、血小板计数（platelet count, PLT）]、性别、年龄、病理分型、TNM分期、淋巴结状态等。本研究选择了50例同期就诊于河北医科大学第四医院的非癌症患者作为对照组。采用SPSS 13.0统计软件进行分析。

结果

NSCLC组与对照组之间所有的凝血功能指标（包括PT、PTA、INR、APTT、Fib、D-D、血小板计数）的血浆水平显示均有统计学差异[除了Fib（ P=0.001, 5）、Plt（ P=0.004, 5），其余指标（ P＜0.001）]。纤维蛋白原水平与NSCLC的组织学亚型之间相关，鳞癌比腺癌的Fib水平明显升高（ P＜0.001）。Ⅲ期、Ⅳ期期比Ⅰ期-Ⅱ期患者的Fib、PLT水平升高（ P＜0.001, P=0.014），APTT缩短（ P＜0.001）。与N0患者相比，N1-N3患者的APTT，明显缩短（ P＜0.001），Fib、D-D水平升高（ P＜0.001, P=0.048）。对生存率的比较研究显示，PT、INR延长（ P=0.032, P=0.001），Fib升高（ P＜0.001），PTA下降（ P=0.005），在统计学上对总生存有明显的不利影响。多因素生存分析显示，在凝血功能指标中INR是唯一的独立预后因素（ P=0.017）。

结论

NSCLC患者往往存在凝血纤溶系统的激活，导致凝血纤溶指标的亚临床改变。肺腺癌患者以及分期为晚期、淋巴结存在转移的NSCLC患者更易出现高血凝状态。PT、INR的延长与NSCLC患者生存率的下降密切相关，INR是NSCLC的独立预后因素，PT、INR可能成为NSCLC的预后指标。

Translated abstract

Background and objective

The activation of coagulation and fibrinolysis is frequently encountered among cancer patients. Such tumors are associated with high risk of invasion, metastases, and negative final outcomes. Non-small cell lung cancer (NSCLC) accounts for approximately 80% to 85% of all lung malignancies. This study aims to investigate the prognostic value of blood coagulation tests for NSCLC and provide a reference to patients on the prevention and treatment of thrombophilia.

Methods

Data were collected from 604 cases of hospitalized patients with histologically confirmed NSCLC from January 2009 to December 2012 at the Fourth Hospital of Hebei Medical University. Data included the related indexes of coagulation function in patients before treatment [( i. e., prothrombin time (PT), prothrombin time activity (PTA), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (Fib), D-dimer, and platelet count)], as well as sex, age, pathological type, TNM stage, and lymph node status. Fifty control subjects without cancer were included in the analysis. Statistical analysis was conducted by using SPSS 13.0 software.

Results

The plasma level of all coagulation tests including D-dimer, Fib, PT, APTT, INR, and platelet counts revealed statistically significant differences between the patient and control group ( P < 0.001 for all variables; P=0.001, 5 and P=0.004, 5 for Fib and platelet counts, respectively). The squamous subtype exhibited high plasma Fib levels ( P < 0.001) compared with adenocarcinoma cell lung cancer patients. Fib and PLT levels increased ( P < 0.001 and P=0.014, respectively), and aPTT decreased ( P < 0.001) in patients at stages Ⅲ and Ⅳ compared with those in patients at stages Ⅰ and Ⅱ. aPTT decreased significantly ( P < 0.001), and Fib and D-dimer levels increased ( P < 0.001 and P=0.048, respectively) in N1-3 patients with NSCLC compared with those of N0 patients. Prolonged PT and INR, high plasma Fib levels, and low PTA levels had statistically significant adverse effects on survival ( P=0.032, P=0.001, P < 0.001, and P=0.005, respectively). Multivariate analyses revealed that only increased INR was associated with a decreased survival rate in the related indexes of coagulation function ( P=0.017).

Conclusion

Patients who have lung adenocarcinoma and/or lymph node metastasis at advanced stages of NSCLC are prone to thrombophilia. Prolonged PT and INR was associated with poor prognosis, and elevated INR was independently associated with a decreased survival rate. PT and INR are promising prognostic markers of NSCLC.