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晚期肺癌患者凝血-纤溶系统的变化及化疗对其的影响

Changes of Coagulation-fibrinolytic System and Effects Produced by Chemotherapy in Advanced Lung Cancer Patients

  • 摘要: 目的 探讨尿激酶纤维蛋白溶酶原激活物(urokinase plasminogen activator, uPA)系统在肺癌患者中的变化,分析并评价其与肺癌患者预后的关系。方法 记录肺癌患者化疗前、后及对照组的凝血指标,并用ELISA法检测各组外周血uPA、 组织型纤维蛋白溶酶原激活物(tissue-type Plasminogen Activator, tPA)、纤维蛋白溶酶原激活剂抑制物-1(Plasminogen Activator Inhibitor-1, PAI-1)浓度。结果 (1)肺癌患者化疗前(A1组)、化疗2周期后(A2组)上述各项凝血-纤溶指标均显著高于正常对照组(B组)( P均 < 0.05);(2)A1组与A2组之间的凝血指标血小板计数(platelet count, PC)、凝血酶原时间(prothrombin time, PT)、活化部分凝血活酶时间(activated partial thromboplastin time, APTT)虽然存在差别,但差别不具有统计学意义(P均 >0.05),化疗2周期后的D-二聚体(D-dimer)、tPA、uPA、PAI-1均显著高于化疗前(P均<0.05);(3)分层分析表明:A2组中治疗进展病例的uPA和D-dimer显著高于临床获益病例(P均<0.05);(4)化疗前、后有显著变化的纤溶指标uPA与D-dimer、tPA、PAI-1之间均有直线正相关性(0.472、0.624、0.575、P 均<0.01),tPA与PAI-1也具有直线正相关关系(r=0.61,P <0.001)。结论 (1)肺癌患者存在凝血-纤溶系统紊乱,化疗可以加重这一异常,且纤溶系统变化更为敏感;(2)血浆低水平的uPA和D-dimer的肺癌患者有较好化疗效果,且两者存在正相关关系,因此两者可能成为提示肺癌患者预后的指标。

     

    Abstract: Objective To explore the changes of urokinase plasminogen activator(uPA) system, and to analyze and evaluate the relationship between uPA system and prognosis. Methods Coagulation indexes of lung cancer patients before and after chemotherapy and the healthy in control group were recorded. Peripheral blood concentration of uPA, tissue-type plasminogen activator(tPA) and plasminogen activator inhibitor-1(PAI-1) were measured by enzyme-linked immunosorbent assay(ELISA). Results All blood coagulation-fibrinolytic indexes of lung cancer patients in both before chemotherapy (Group A1 ) and after two cycles of chemotherapy ( Group A2) were significantly higher than that in normal control group (Group B)(P<0.05). Comparing Group A1 with Group A2, the coagulation indexes of platelet count(PC), prothrombin time(PT), activated partial thromboplastin time(APTT) had no significant difference(P>0.05). However, blood concentrations of D-dimer, tPA, uPA, PAI-1 in Group A2 were significantly higher than those in Group A1(P<0.05). In Group A2, the hierarchical analysis showed that both of plasma concentrations of uPA and D-dimer in progressive treatment cases were higher than those in clinical benefit cases (all P<0.05). uPA and D-dimer, tPA, PAI-1 which were changed significantly before and after chemotherapy were positively linear correlated, and the correlation coefficients were 0.472, 0.624, 0.575(all P<0.01). Meanwhile tPA and PAI-1 also were positively linear correlated(r= 0.61, P<0.001). Conclusion Lung cancer patients are suffered with dysfunction of coagulation-fibrinolytic system, and chemotherapy may exacerbate this anomaly, especially more sensitive to changes in fibrinolytic parameters. Low plasma concentrations of uPA and D-dimer in lung cancer patients contribute to good curative effect of chemotherapy, with positive correlation. Therefore, uPA D-dimer might be prompt indexes of the prognosis of lung cancer patients.

     

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