头颈部恶性肿瘤复发转移患者止凝血功能的研究

The Study of Heamostatic Function in Patients with Head and Neck Tumor with Relapse or Metastasis

目的探索其止凝血机制的常规检测指标及分子标志物的改变在头颈部恶性肿瘤有无复发、转移不同时期患者的诊断、复发转移和预后判断中的意义。方法对30例正常对照组人群及84例头颈部恶性肿瘤患者进行常规止凝血功能的检测,包括PLT、PT、aPTT、TT、Fbg及血小板活化、凝血、抗凝血和纤溶指标的分子标志物的检测,包括GMP-140、TF、TAT、TFPI、TpP、PAP、u-PA、t-PA、PAI-1、D-D含量和凝血因子Ⅱ、Ⅴ、Ⅶ、Ⅷ、Ⅸ、Ⅹ和Ⅺ活性及抗凝血酶AT活性。结果 (1)在头颈部恶性肿瘤组患者中均有Fbg升高(P<0.05),且在疾病复发转移后更加明显(P<0.01),同时在这组患者中出现PT、aPTT的缩短(P<0.05)。(2)在头颈部恶性肿瘤组中均存在着GMP-140、TF、TAT和TpP的升高(P<0.05),且在疾病复发转移组中更明显(P<0.05或P<0.01),同时在这组患者中又有凝血因子Ⅶ、Ⅹ活性的升高和AT活性的降低(P<0.05)。(3)在头颈部恶性肿瘤组中存在着纤溶指标PAP、u-PA、t-PA和D-D含量的升高(P<0.05),在肿瘤复发转移后这些指标升高更明显(P<0.05或P<0.01),同时在这组患者中又出现了PAI-1含量的升高(P<0.05)。结果头颈部恶性肿瘤患者体内存在着血小板、凝血、抗凝血和纤溶方面的止凝血功能的异常。表现为血小板活化、凝血激活、抗凝血抑制和纤溶系统的活化。常规止凝血功能的指标除Fbg含量变化与肿瘤复发转移明显相关外,其余指标变化不大。血小板活化、凝血、抗凝血和纤溶系统分子标志物水平的改变在头颈部恶性肿瘤患者合并有复发转移者中变化更加明显,可作为头颈部恶性肿瘤预测、肿瘤复发和转移及判断预后的敏感指标。

Objective To investigate the haemostatic changes of patients with head and neck at the different stages,such as disease in progress,relapse or metastasis.Methods Routine haemostatic tests were conducted among 84 patients with head and neck tumor.30 healthy volunteers were enrolled as controls.The tests included the plasma concentration of PLT,PT,aPTT,TT,Fbg.Some coagulable and fibrinolytic molecular markers,such as GMP-140,TF,TAT,TFPI,TpP,PAP,u-PA,t-PA,PAI-1 were also measured.The activities of coagulation factors Ⅱ,Ⅴ,Ⅶ,Ⅷ,Ⅸ,Ⅹ,Ⅺ and AT were evaluated as well.Results（1）The plasma levels of Fbg were elevated in head and neck tumor patients（P0.05）,while in the relapse and metastasis groups,the levels were significantly higher than that of the control（P0.01）.At the same time,PT,aPTT were shortened（P0.05）.（2） The plasma levels of GMP-140,TF,TAT and TpP were elevated in head and neck tumor patients（P0.05）.Meanwhile,in relapse and metastasis groups,the levels were significantly higher than that of the control（P0.05 or P0.01）.Increased activity of coagulation factors Ⅶ,Ⅹand decreased activity of AT also took place at the same time.（3） Compared with normal control,the patients with head and neck tumor had higher concentrations of fibrinolytic parameters,such as PAP,u-PA,t-PA and D-dimer（P0.05）.While in the relapse and metastasis groups,all these parameters raised more remarkably（P0.05 or P0.01）.Furthermore,the concentration of fibrinogen inhibitor PAI-1 was also elevated（P0.05）.Conclusion Patients with head and neck tumor may harbor many alterations of hemostasis.These alterations included increased platelet aggregation and activation,abnormal activation of coagulation cascade,decreased synthesis of anticoagulant proteins,abnormal activation of fibrinolysis.The plasma level of Fbg plays an important role in predicting the relapse and metastasis of disease.Other changes of routine Results seems to have no definite impact on the progess of the disease.Levels of the molecular markers of platelet activation,coagulable and fibrinolitic system changed remarkably in patients with relapse and metastasis.Therefore,these markers could be considered as sensitive predicators of progress.