血液系统恶性肿瘤患者止凝血功能的研究

目的 动态观察血液系统恶性肿瘤患者在疾病缓解和进展不同时期的止凝血功能的变化,以探索其止凝血机制的常规检测指标及分子标志物的改变对血液系统恶性肿瘤患者的诊断、疾病进展和预后的临床意义.方法 对30例正常对照组人群及44例血液系统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、D-D含量和凝血因子Ⅱ、Ⅴ、Ⅶ、Ⅷ、Ⅸ、Ⅹ和Ⅺ活性及AT活性.结果 1.在血液系统恶性肿瘤组及其疾病缓解期组中存在着Fbg的升高（P＜0.05）,至疾病进展期中PLT、Fbg出现了下降（P＜0.05）.且出现了PT、aPTT的延长（P＜0.05）;2.在血液系统恶性肿瘤组中,GMP-140、TF、TAT、TFPI和TpP含量的升高及AT活性的降低,在疾病进展期中变化更明显（P＜0.05或P＜0.01）,同时有凝血因子Ⅴ、Ⅵ、Ⅷ、Ⅸ的降低（P＜0.05）,而在疾病缓解期时同样存在着GMP-140、TF、TpP的升高及AT活性的降低（P＜0.05）;3.在血液系统恶性肿瘤组中同样存在着纤溶指标PAP、u-PA、t-PA和D-D的含量的升高（P＜0.05）,疾病进展期升高得更明显（P＜0.05或P＜0.01）,且同时出现了纤溶酶原抑制物PAI-1含量的升高（P＜0.05）.结论 血液系统恶性肿瘤患者体内同时存在着血小板、凝血、抗凝和纤溶方面的止凝血功能的异常.表现为血小板数量下降、功能活化、凝血激活、抗凝血降低和纤溶系统的活化.在血液系统恶性肿瘤中常规止凝血指标PLT、Fbg的变化与疾病的进展密切相关.而血小板活化、凝血抗凝和纤溶系统的分子标志物水平的改变对其疾病合并有止凝血功能异常的意义更明显,可作为血液系统恶性肿瘤的疾病的进展和缓解的敏感指标.

The Study of Heamostatic Function in Patients with Hematological Malignancy

Objective To investigate the homeostatic changes of patients with hematological malignan- cy at the different stages between progress or relapse;Some routine homeostatic tests were conducted and mo- lecular markers were measured, in order to evaluate the relationships with the diagnosis, progress and progno- sis. Methods Routine haemostatic tests were conducted among 44 patients with hematological malignancy. 30 healthy volunteers were taken as controls. The test included the plasma concentration of PLT, PT, aPTT, Yl＇, Fbg. Some coagulable and fibrinolytic molecular markers. Such as GMP- 140, TF, TAT, TFPI, TpP, PAP, u- PA, t- PA, PAI, D-dimer were also measured. The activities of coagulation factors II , V, VI, VIU, IX, X, XI, and AT ware evaluated as well. Results （ 1 ） The plasma levels of Fbg were elevated in the group of patients with he- matological malignancy and the states in remission （ P 〈 0.05 ）, However, when the disease was in progress, the concentration of PLT, Fbg decreased （ P 〈 0.05 or P 〈 0.01 ） , PT and aPTT prolonged （ P 〈 0.05 ）. （ 2 ） The plasma levels of GMP-140 ,TF ,TAT and TpP were elevated in the group of patients with hematological malig- nancy and the states in remission（ P 〈 0.05 ） , when the disease was in progress the changes were more signifi- cantly（P 〈0.05 or P 〈0.01 ）,meanwhile decreased activity of coagulation factors V, V], ~l, IX took place （P 〈 0.05 ）. When the disease was in remission, similar changes of GMP-140, TF, TpP and AT were obtained （P 〈 0.05）. However, the activities of coagulation factors V and ]X were elevated （P 〉 0.05）. （3） Compared with the normal control, the patients with hematological malignancy had higher concentrations of fi- brinolytic parameters, such as PAP, u- PA, t- PA and D- dimer （ P 〈 0.05 ）, while in the relapse, all these parameters raised more remarkably（ P 〈 O. 05 or P 〈 O. 01 ）. Furthermore, the concentration of fibrinogen inhibi- tor PAI-1 was also elevated （P 〈 0.05 ）. Conclusion Patients with hematological malignancy may harbor many alterations of hemostasis. These alteration could be categorized as increased platelet aggregation and acti- vation, abnormal activation of coagulation cascade, decreased synthesis of anticoagulant proteins, abnormal acti- vation of fibrinolysis. In the group of patients with hematological malignancy, the alterations of PLT and Fbg are closely correlated with the progress of disease, variable levels of the molecular markers of platelet activation, coagulable and fibrinolitic system could indicate the progress.