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中华胸部外科电子杂志 ›› 2015, Vol. 02 ›› Issue (01) : 40 -47. doi: 10.3877/cma.j.issn.2095-8773.2015.01.008

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论著

术前凝血检测对于评估根治性非小细胞肺癌患者预后的意义
索海进1, 张华1, 朱建权1, 刘俊1, 王长利1,()   
  1. 1. 300060 天津医科大学肿瘤医院肺部肿瘤科
  • 收稿日期:2015-01-12 出版日期:2015-02-28
  • 通信作者: 王长利

Prognostic significance of preoperative coagulation assays in patients with non-small cell lung cancer after complete resection

Haijin Suo1, Hua Zhang1, Jianquan Zhu1, Jun Liu1, Changli Wang1,()   

  1. 1. Department of Lung Cancer, Cancer Institute and Hospital of Tianjin Medical University, Tianjin 300060, China
  • Received:2015-01-12 Published:2015-02-28
  • Corresponding author: Changli Wang
  • About author:
    Corresponding author: Wang Changli, Email:
引用本文:

索海进, 张华, 朱建权, 刘俊, 王长利. 术前凝血检测对于评估根治性非小细胞肺癌患者预后的意义[J/OL]. 中华胸部外科电子杂志, 2015, 02(01): 40-47.

Haijin Suo, Hua Zhang, Jianquan Zhu, Jun Liu, Changli Wang. Prognostic significance of preoperative coagulation assays in patients with non-small cell lung cancer after complete resection[J/OL]. Chinese Journal of Thoracic Surgery(Electronic Edition), 2015, 02(01): 40-47.

目的

评估术前常规凝血功能检测水平与非小细胞肺癌(NSCLC)患者行根治性完整切除术后总生存率的相关性。

方法

选取2004年1月至2008年12月在天津医科大学肿瘤医院行完全性切除手术的NSCLC患者754例。利用Kruskall-Wallis和Mann-Whitney U检验,评价术前常规凝血检测水平与其他变量的相关性,并且通过单变量和多变量分析确定凝血功能的术前水平和总体生存率之间的关联。

结果

所有术前常规凝血检测指标(血浆凝血酶原时间、国际标准化比值、活化部分凝血活酶时间、凝血酶时间、纤维蛋白原、D-二聚体)水平与NSCLC患者T分期及临床分期均存在相关性。单因素分析显示,术前凝血试验中血浆凝血酶原时间(χ2=8.254,P=0.004)和国际标准化比值(χ2=5.4.4,P=0.020)延长,以及异常升高的纤维蛋白原(χ2=9.184,P=0.002)和D-二聚体(χ2=9.184,P=0.002)水平提示预后较差。多变量模型证实术前D-二聚体为NSCLC患者预后的独立因素(OR=1.274,95%CI:1.040~1.559,P=0.019)。

结论

术前凝血检测中血浆凝血酶原时间和国际标准化比值延长以及纤维蛋白原和D-二聚体水平升高提示NSCLC患者预后不良,而术前凝血检测中D-二聚体是行根治性手术NSCLC患者的独立预后因素。

Objective

To evaluate the correlation between preoperative coagulation assays’ levels and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) after complete resection.

Methods

A retrospective study of 754 patients with NSCLC undergoing complete resection was conducted at the Tianjin Medical University Cancer Institute and Hospital from January 2004 to December 2008. The correlation of preoperative coagulation assays’ levels with other variables was evaluated by Kruskall-Wallis and Mann-Whitney U test. Univariate and multivariate analysis was employed to determine the association between the preoperative level of coagulation factors and OS.

Results

All preoperative coagulation tests’ levels prothrombin time (PT); international normalized ratio (INR); activated partial thromboplastin time (APTT); thrombin time (TT); fibrinogen (Fbg); D-dimer)were associated with T stage and clinical stage. Univariate analysis of survival showed that preoperative prolonged prothrombin time (PT) (χ2=8.254, P=0.004) and International Normalized Ratio (INR) (χ2=5.404, P=0.020), and abnormally elevated fibrinogen (Fbg) (χ2=9.184, P=0.002) and D-dimer (χ2=9.184, P=0.002) were associated with a poor prognosis. And the multivariate model confirmed preoperative D-dimer was an independent prognostic factor for the patients with NSCLC(OR=1.274, 95%CI: 1.040-1.559, P=0.019).

Conclusions

Preoperative prolongation of PT and INR, and elevation of Fbg and D-dimer are associated with decreased survival in NSCLC patients, and preoperative plasma D-dimer level is an independent prognostic factor of survival in patients with NSCLC after complete resection.

表1 非小细胞肺癌患者临床病理学以及血液学特征
表2 非小细胞肺癌患者各项凝血指标的临床病理学特征
表3 非小细胞肺癌患者凝血功能指标与各项变量之间的相关性(中位值)
变量 PT(s) INR APTT(s) TT(s) Fbg(g/L) D-二聚体(μg/L) PLT(×109/L)
年龄 ? ? ? ? ? ? ?
? ≤61岁 10.5 0.950 26.40 15.6 3.424 190 245
? >61岁 10.7 0.960 26.40 15.4 3.807 192 235
? χ2 5.305 4.710 0.006 3.175 6.062 0.001 1.194
? P 0.058 0.048 0.690 0.212 0.001 0.820 0.072
性别 ? ? ? ? ? ? ?
? 男性 10.6 0.955 26.70 15.7 3.807 197 243
? 女性 10.5 0.950 25.75 15.5 3.360 178 236
? χ2 10.276 0.274 4.300 0.227 19.426 2.052 0.059
? P 0.009 0.176 0.018 0.155 0.001 0.063 0.357
吸烟史 ? ? ? ? ? ? ?
? 10.5 0.950 25.95 15.4 3.258 171 231
? 10.6 0.960 26.70 15.4 3.879 201 244
? χ2 0.077 0.429 3.004 0.197 32.633 1.205 0.226
? P 0.085 0.511 0.073 0.829 0.001 0.150 0.058
病理类型 ? ? ? ? ? ? ?
? 鳞癌 10.7 0.970 27.10 15.4 4.000 206 248
? 腺癌 10.4 0.940 25.60 15.6 3.109 172 227
? 其他 10.6 0.960 27.05 15.3 3.954 192 254
? χ2 15.277 14.207 17.410 1.856 70.680 10.480 14.465
? P 0.000 0.001 0.000 0.511 0.000 0.003 0.000
肿瘤大体位置 ? ? ? ? ? ? ?
? 周围型 10.5 0.950 26.30 15.5 3.424 192 230
? 中心型 10.7 0.970 26.90 15.2 4.031 189 265
? χ2 4.244 5.012 2.681 3.639 25.581 2.417 5.180
? P 0.034 0.010 0.032 0.004 <0.001 0.230 0.000
肿瘤部位 ? ? ? ? ? ? ?
? 左侧 10.6 0.950 26.20 15.4 3.606 196 239
? 右侧 10.5 0.950 26.60 15.4 3.606 188 242
? χ2 0.002 0.045 0.478 0.170 0.045 0.067 0.967
? P 0.729 0.821 0.483 0.603 0.820 0.934 0.934
T分期 ? ? ? ? ? ? ?
? T1 10.4 0.940 25.50 15.7 3.208 173 227
? T2 10.7 0.970 26.90 15.3 3.878 194 243
? T3-4 11.1 1.010 28.45 15.3 4.564 251 284
? χ2 36.927 39.135 33.285 15.326 75.777 17.747 33.256
? P 0.001 0.000 0.000 0.001 0.000 0.001 0.000
淋巴结转移 ? ? ? ? ? ? ?
? 10.5 0.950 26.40 15.4 3.543 173 240
? 10.6 0.960 26.45 15.4 3.716 214 241
? χ2 2.277 1.122 0.017 0.022 0.833 1.230 1.520
? P 0.115 0.045 0.645 0.718 0.423 0.120 0.544
病理分期 ? ? ? ? ? ? ?
? 10.4 0.940 25.90 15.6 3.367 171 230
? 10.7 0.970 27.35 15.3 4.000 190 258
? ⅢA 10.7 0.960 26.70 15.4 3.738 237 245
? χ2 11.310 9.488 12.626 7.675 26.714 6.299 16.639
? P 0.000 0.000 0.000 0.000 0.000 0.002 0.003
血红蛋白(g/L) ? ? ? ? ? ? ?
? 降低(<120) 10.8 0.970 29.00 15.45 3.978 196 292
? 正常(≥120) 10.5 0.950 26.30 15.40 3.606 191 238
? χ2 7.322 13.693 7.255 0.045 3.472 1.152 30.152
? P 0.001 0.000 0.000 0.485 0.024 0.157 0.000
乳酸脱氢酶(IU/L) ? ? ? ? ? ? ?
? 正常(≤240) 10.6 0.950 26.40 15.4 3.543 189 240
? 升高(>240) 10.6 0.970 26.30 15.2 4.372 219 247
变量 PT(s) INR APTT(s) TT(s) Fbg(g/L) D-二聚体(μg/L) PLT(×109/L)
? χ2 0.004 0.609 0.006 0.605 13.518 3.664 0.007
? P 0.33 0.277 0.409 0.831 0.000 0.158 0.332
白细胞计数(×106/L) ? ? ? ? ? ? ?
? 正常(≤10000) 10.5 0.950 26.30 15.4 3.483 192 235
? 升高(>10000) 11.0 0.990 27.50 15.2 4.681 187 291
? χ2 12.885 14.329 5.607 0,852 34.512 0.089 37.983
? P 0.000 0.000 0.007 0.109 0.000 0.838 0.000
表4 NSCLC患者的5年生存率单因素分析
变量 例数 5年生存率(%) χ2 P 变量 例数 5年生存率(%) χ2 P
年龄 ? ? 0.725 0.424 白细胞计数(×106/L) ? ? 3.336 0.068
? ≤61岁 395 48.9 ? ? ? 正常(≤10000) 665 49.2 ? ?
? >61岁 359 47.5 ? ? ? 升高(>10000) 86 41.8 ? ?
性别 ? ? 0.339 0.607 中性粒细胞(×106/L) ? ? 1.010 0.315
? 男性 508 48.2 ? ? ? 正常(≤7000) 673 48.4 ? ?
? 女性 246 48.3 ? ? ? 升高(>7000) 70 44.8 ? ?
吸烟史 ? ? 1.541 0.234 单核细胞(×106/L) ? ? 9.455 0.002
? 260 50.5 ? ? ? 正常(≤550) 412 52.2 ? ?
? 494 47.3 ? ? ? 升高(>550) 337 43.2 ? ?
病理类型 ? ? 1.627 0.469 淋巴细胞(×106/L) ? ? 1.035 0.349
? 鳞癌 373 47.9 ? ? ? 降低(<1500) 149 45.2 ? ?
? 腺癌 287 49.7 ? ? ? 正常(≥1500) 599 48.9 ? ?
? 其他 94 44.8 ? ? 乳酸脱氢酶(IU/L) ? ? 11.754 0.001
肿瘤大体位置 ? ? 5.796 0.017 ? 正常(≤240) 686 49.5 ? ?
? 周围型 535 50.9 ? ? ? 升高(>240) 63 33.6 ? ?
? 中心型 219 42.5 ? ? 碱性磷酸酶(IU/L) ? ? 1.918 0.166
肿瘤部位 ? ? 2.141 0.127 ? 正常(≤132) 733 49.1 ? ?
? 左侧 311 46.4 ? ? ? 升高(>132) 19 28.4 ? ?
? 右侧 443 49.5 ? ? PT(s) ? ? 8.254 0.004
手术类型 ? ? 3.908 0.036 ? 正常(≤10.6) 409 52.2 ? ?
? 全肺切除术 103 49.5 ? ? ? 升高(>10.6) 345 43.6 ? ?
? 肺叶切除术 651 41.7 ? ? INR ? ? 5.404 0.018
病理分期 ? ? 114.267 <0.001 ? 正常(≤1.0) 382 51.9 ? ?
? 325 64.9 ? ? ? 升高(>1.0) 372 44.8 ? ?
? 156 51.4 ? ? APTT(s) ? ? 2.736 0.098
? ⅢA 273 27.3 ? ? ? 正常(≤26.4) 379 50.3 ? ?
T分期 ? ? 19.447 <0.001 ? 升高(>26.4) 375 45.7 ? ?
? T1 283 55.2 ? ? TT(s) ? ? 2.272 0.132
? T2 403 46.3 ? ? ? 正常(≤15.4) 386 46.1 ? ?
? T3-4 68 32.8 ? ? ? 升高(>15.4) 368 50.3 ? ?
淋巴结转移 ? ? 86.917 <0.001 Fbg(g/L) ? ? 9.184 0.002
? 418 62.1 ? ? ? 正常(≤3.6) 382 52.5 ? ?
? 336 31.4 ? ? ? 升高(>3.6) 372 43.7 ? ?
化疗a ? ? 1.060 0.327 D-二聚体(μg/L) ? ? 9.184 0.002
? 388 46.1 ? ? ? 正常(≤100) 412 54.1 ? ?
? 366 50.4 ? ? ? 升高(>100) 323 41.6 ? ?
化疗b ? ? 6.892 0.007 PLT(×109/L) ? ? 0.158 0.691
? 260 40.3 ? ? ? 正常(≤240) 376 48.7 ? ?
? 169 30.6 ? ? ? 升高(>240) 375 47.8 ? ?
血红蛋白(g/L) ? ? 0.457 0.499 ? ? ? ? ? ?
? 降低(<120) 78 47.6 ? ? ? ? ? ? ? ?
? 正常(≥120) 673 48.3 ? ? ? ? ? ? ? ?
表5 NSCLC患者的多因素分析
图1 不同NSCLC患者预后比较。A为不同PT组间比较;B为不同INR组间比较;C为不同Fbg组间比较;D为不同D-二聚体组间比较
[1]
Lyman GH, Khorana AA. Cancer, clots and consensus: new understanding of an old problem[J]. J Clin Oncol, 2009, 27(29):4821-4826.
[2]
Lyman GH, Bettigole RE, Robson E, et al. Fibrinogen kinetics in patients with neoplastic disease[J]. Cancer,1978,41(3):1113-1122.
[3]
Rak J, Milsom C, May L, et al. Tissue factor in cancer and angiogenesis: the molecular link between genetic tumor progression, tumor neovascularization, and cancer coagulopathy[J]. Semin Thromb Hemost, 2006,32(1):54-70.
[4]
Winter PC. The pathogenesis of venous thromboembolism in cancer: Emerging links with tumor biology[J]. Hematol Oncol, 2006,24(3):126-133.
[5]
Dvorak HF. Thrombosis and cancer[J]. Hum Pathol, 1987,18(3):275-284.
[6]
Amirkhosravi A, Meyer T, Amaya M et al. The role of tissue factor pathway inhibitor in tumor growth and metastasis[J].Semin Thromb Hemost, 2007,33(7):643-652.
[7]
Rickles FR, Levine MN, Dvorak HF. Abnormalities of hemostasis in malignancy// In: Colman RW, Hirsh J, Marder VJ, et al. Hemostasis and thrombosis.Basic principles and clinical practice[M]. 4th ed. Philadelphia: Lippincott Williams and Wilkins, 2001: 1131-1152.
[8]
Buccheri G, Ferrigno D, Ginardi C, et al. Haemostatic abnormalities in lung cancer: prognostic implications[J]. Eur J Cancer, 1997,33(1):50-55.
[9]
Seitz R, Rappe N, Drus M, et al. Activation of coagulation and fibrinolysis in patients with lung cancer: relation to tumor stage and prognosis[J]. Blood Coagul Fibrinolysis, 1993,4(2):249-254.
[10]
Gabazza EC, Taguchi O, Yamakami T, et al. Evaluating prethrombotic state in lung cancer using molecular markers.Chest, 1993,103(1):196-200.
[11]
Brambilla E, Travis WD, Colby TV, et al. The new World Health Organization classification of lung tumors[J]. Eur Respir J, 2001,18(6):1059-1068.
[12]
Detterbeck FC, Boffa DJ, Tanoue LT. The new lung cancer staging system[J]. Chest, 2009, 136(1):260-271.
[13]
Goad KE, Gralnick HR. Coagulation disorders in cancer[J]. Hematol Oncol Clin North Am, 1996,10(2):457-484.
[14]
Buccheri G, Torchio P, Ferringo D. Plasma levels of D-dimer in lung cancer[J]. Cancer, 2003,97(12):3044-3052.
[15]
Taguchi O, Gabazza EC, Yasui H, et al. Prognostic significance of plasma D-dimer levels in patients with lung cancer[J]. Throax, 1997,52(6):563-565.
[16]
Tas F, Kilic L, Serilmez M, et al. Clinical and prognostic significance of coagulation assays in lung cancer[J]. Respir Med, 2013,107(3):451-457.
[17]
Jones JM, McGonigle NC, McAnespie M, et al. Plasma fibrinogen and serum C-reactive protein are associated with non-small cell lung cancer[J]. Lung Cancer, 2006, 53(1): 97-101.
[18]
Edwards RL, Rickles FR, Moritz TE, et al. Abnormalities of blood coagulation tests in patients with cancer[J]. Am J Pathol, 1987,88(5):596-602.
[19]
Gouin-Thibault I, Samama MM. Laboratory diagnosis of the thrombophilic state in cancer patients[J]. Sem Throm Hemost, 1999,25(2):167-172.
[20]
Pedersen LM, Milman N. Prognostic significance of thrombocytosis in patients with primary lung cancer[J]. Eur Respir J, 1996,9(9):1826-1830.
[21]
Tomita M, Shimizu T, Hara M, et al. Prognostic impact of thrombocytosis in resectable non-small cell lung cancer[J]. Interact Cardiovasc Thorac Surg, 2008, 7(4):613-615.
[22]
Cakar B, Karaoglanoglu M, Sayici Y, et al. The prognostic value of thrombocytosis in newly diagnosed lung cancer patients: a retrospective analysis[J]. J BUON, 2011, 16(4):677-681.
[23]
Owen CAJ, Bowie EJW, Thompson JHJ.The diagnosis of bleeding disorders[M]. Boston: Little, Brown & Company, 1975.
[24]
Ferrigno D, Buccheri G, Ricca I. Prognostic significance of blood coagulation tests in lung cancer[J]. Eur Respir J, 2001,17(4):667-673.
[25]
Staton CA, Brown NJ, Lewis CE. The role of fibrinogen and related fragments in tumor angiogenesis and metastasis[J]. Expert Opin Biol Ther, 2003,3(7):1105-1120.
[26]
Yamaguchi T, Yamamoto Y, Yokota S et al. Involvement of interleukin-6 in the elevation of plasma fibrinogen levels in lung cancer patients[J]. Jpn J Clin Oncol, 1998,28(12):740-744.
[27]
Zhao J, Zhao M, Jin B, et al. Tumor response and survival in patients with advanced non-small-cell lung cancer: the predictive value of chemotherapy-induced changes in fibrinogen[J]. BMC, 2012,12:330.
[28]
Francis CW, Marder VJ. Williams Hematology[M]. New York: McGraw-Hill,1995:1252-1260.
[29]
Blackwell K, Haroon Z, Broadwater G, et al. Plasma D-dimer levels in operable breast cancer patients correlate with clinical stage and axillary lymph node status[J]. J Clin Oncol, 2000,18(3):600-608.
[30]
Antoniou D, Pavlakou G, Stathpoulos G, et al. Predictive value of D-dimer plasma levels in response and progressive disease in patients with lung cancer[J]. Lung Cancer, 2006,53(2):205-210.
[31]
Altiay G, Ciftci A, Demir M, et al. High plasma D-dimer level is associated with decreased survival in patients with lung cancer[J]. Clin Oncol,2007,19(7):494-498.
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