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血栓标志物评估恶性肿瘤患者静脉血栓风险

Estimation of venous throm boembolism risk with thrombotic biomarkers in cancer patients

摘要:

目的:研究血栓标志物对恶性肿瘤患者静脉血栓栓塞( VTE)风险的评估价值。方法选择2009—2012年就诊于天津医科大学总manbet官网登录 的恶性肿瘤患者1473例,采用ACL TOP 700型血液凝固仪测定血管性血友病因子抗原含量( vWF:Ag)、凝血因子Ⅶ活性( FⅦ:A)、凝血因子Ⅷ活性( FⅧ:A)、蛋白C活性(PC:A)、蛋白S 活性(PS:A)和抗凝血酶活性(AT:A),采用法国梅里埃VIDAS荧光免疫分析仪测定血浆D-二聚体( D-D)水平。采用受试者工作特征曲线(ROC 曲线)评价各项指标的诊断性能,对预后因素的分析采用Cox回归模型,采用Kaplan-Meier曲线进行生存分析。结果除其他未分型肿瘤外,各类型肿瘤患者中vWF:Ag、D-D和FⅦ:A水平均高于对照组(均P<0.05)。除肾癌、前列腺癌、淋巴瘤和其他肿瘤外,各类型肿瘤患者中F Ⅷ:A水平均高于对照组(均P<0.05)。除脑胶质瘤、乳腺癌、胃癌、肾癌和其他肿瘤外,各类型肿瘤患者中PC:A水平均低于对照组(均P<0.05)。除脑胶质瘤、乳腺癌、前列腺癌、淋巴瘤和其他肿瘤外,各类型肿瘤患者中PS:A水平均低于对照组(均P<0.05)。各类型肿瘤患者中AT:A水平均低于对照组(均P<0.05)。 vWF:Ag诊断恶性肿瘤患者VTE的临界值为192%时,ROC曲线下面积为0.828(95%CI为0.716~0.939);D-D临界值为1484 ng/ml时,ROC曲线下面积为0.915(95%CI为0.840~0.988);PC:A临界值为75.2%时,ROC曲线下面积为0.764(95%CI为0.630~0.898)。 Cox比例风险模型显示,年龄、手术、化疗和D-D水平是恶性肿瘤患者随访3个月内发生VTE的独立风险因素。血浆D-D水平高于临界值的恶性肿瘤患者VTE累计发生概率显著增高。结论恶性肿瘤患者血浆D-D水平显著增高,并与恶性肿瘤患者的血栓风险分层和VTE风险概率密切相关,具有良好的诊断性能,可作为评价恶性肿瘤患者随访3个月内VTE风险的有效指标。

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abstracts:

Objective To assess the value of thrombotic biomarkers in estimation of venous thromboembolism ( VTE) risk in cancer patients.Methods A total of 1473 cancer patients treated in the Tianjin Medical University General Hospital from 2009 to 201 were selected, including 845 males and 628 females in the age of 56±17 years.The activities of von Willebrand factor antigen ( vWF:Ag) , factorⅦ( FⅦ:A), factor Ⅷ (FⅧ:A), antithrombin (AT:A), protein C (PC:A) and protein S (PS:A) were assayed using an ACL TOP 700 blood coagulation analyzer.The level of D-dimer ( D-D) was assayed using the Biomerieux Mini Vidas Automated Immunoassay Analyzer.Receiver operating characteristic curve ( ROC) was used to analyze the diagnostic performance of the parameters.Cox regression analysis model was applied to evaluate the effect on prognosis, and Kaplan-Meier curve was used to implement the survival analysis.Results The levels of vWF:Ag, D-D, and FⅧ:A were significantly higher in all the specified tumor groups ( except the other tumor group ) than that of the control groups ( P<0.05 ) .FⅧ:A was significantly higher than that in the control group in all tumor groups except the renal carcinoma, prostatic cancer, lymphoma groups and the other tumor group ( P<0.05) .The PC:A level was significantly lower in all tumor patients groups than in the control group, except glioma, breast cancer, gastric carcinoma, renal carcinoma and the other tumors groups ( P<0.05) .The PS:A level was significantly lower in all tumor groups than in the control group, except the glioma, breast cancer, prostatic cancer, lymphoma and the other tumors groups (P<0.05).The AT:A level was significantly lower in all tumor groups than in the control&nbsp;group (P<0.05).When the optimum cut-off point of vWF:Ag for VTE diagnosis was 192%in the cancer group, the area under ROC curve=0.828 ( 95%CI:0.716 to 0.939) .When the optimum cut-off point of D-dimer for VTE diagnosis was 1484 ng/ml in the cancer group, the area under ROC curve=0.915 ( 95%confidence interval: 0.840 to 0.988).When the optimum cut-off point of PC:A for VTE diagnosis was 75.2%in the cancer group, the area under ROC curve=0.764 ( 95%confidence interval:0.630 to 0.898) . The Cox analysis showed that age, surgery, chemotherapy and D-dimer were independent risk factors for VTE event within three months in cancer patients.The cumulative probability of VTE was increased significantly in the cancer patients if whose plasma D-dimer level was over the cut-off value.Conclusions The plasma D-dimer level is obviously increased in cancer patients, and there is a relevance to thrombosis risk stratification and VTE cumulative probability.It is with good diagnostic performance, and may be used as an effective marker in estimation of VTE risk within 3 months in cancer patients.

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