肺癌和卵巢癌患者血栓相关标志物的实验研究
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摘要
血栓形成是恶性肿瘤的常见并发症之一和第二死亡原因,已有文献报道卵巢癌和肺癌并发静脉血栓发生率分别为10.6%和4.4%[1]。一系列病理、实验和临床研究证实了恶性肿瘤与凝血、抗凝、纤溶系统功能改变有密切的关系,本实验选择凝血因子Ⅷ(coagulation factorⅧ,FⅧ),凝血因子IX (coagulation factor IX,FIX),血管性血友病因子(von Willebrand factor, vWF),血栓前体蛋白(thrombus precursor protein TpP)作为研究观察项目,以求证四项反映血栓前状态的指标在肺癌和卵巢癌病程中的变化情况。
目的
1观察肺癌和卵巢癌患者中血浆FⅧ活性(FⅧ:C)、FIX活性(FIX:C)、vWF抗原含量(vWF:Ag)、TpP含量变化与肺癌分期分型及卵巢癌的相关性。
2探讨肺癌和卵巢癌患者手术前和手术后血浆FⅧ:C、FIX:C、vWF:Ag与TpP含量的变化及临床意义。
3通过对肺癌和卵巢癌患者血浆凝血因子FⅧ:C、FIX:C、vWF:Ag与TpP含量研究,为肺癌和卵巢癌患者血栓前状态的预防,诊断,治疗提供帮助。
方法
选择均经病理组织学或细胞学确诊38例肺癌和11例卵巢癌患者,男性26例,女性23例,平均年龄61±8.9岁,健康对照组20例,男性11例,女性9例,平均年龄57±8.2岁。三组间年龄无显著性差异。按照肺癌TNM分期和肺癌临床分期,肺癌Ⅰ～Ⅱ期病例13例,Ⅲ～Ⅳ期病例25例。病理分型:鳞癌11例,腺癌21例,小细胞癌6例。取外周静脉血4ml,注入含有柠檬酸钠抗凝液(1:9)试管内,提取血浆。用凝固法在Stago全自动凝血仪上测定血浆FⅧ活性、FIX活性,用ELISA(enzyme-linked immunosorbent assay)方法测定血浆VWF抗原含量、TpP含量。肿瘤组中接受手术治疗的患者于术后第7天采静脉血4ml,注入含有柠檬酸钠抗凝液(1:9)试管内,处理同前。统计学分析:所得的数据均用均数±标准差表示,组间比较采用独立样本t检验或单因素方差分析,手术前后样本采用配对t检验。
结果
1肺癌患者血浆FⅧ:C,FIX:C,vWF:Ag﹑TpP含量明显高于健康对照组(FⅧ:C 150.61±50.06% VS 77.4±19.8%,FIX:C 143.45±27.41%VS 102.75±9.61%,vWF 217.74±74.84% VS 140.29±53.54%,TpP 10.14±2.07μg/ml VS 3.58±1.59μg/ml),并存在显著差异(均P<0.01)。
2卵巢癌患者血浆FⅧ:C﹑FIX:C﹑vWF:Ag﹑TpP含量明显高于健康对照组(FⅧ:C185.18±90.12 VS 77.4±19.8%, FIX:C 146±40.1 VS 102.75±9.61%,vWF 221.23±109.91 VS140.29±53.54%,TpP 10.1±1.7μg/ml VS 3.58±1.59μg/ml),并存在显著差异( P<0.05)。
3肺癌Ⅰ～Ⅱ期患者血浆FⅧ:C,FIX:C,vWF:Ag﹑TpP含量明显高于健康对照组,有显著性差异,(P<0.05)肺癌Ⅲ～Ⅳ期与Ⅰ～Ⅱ期患者比较,血浆FⅧ:C﹑vWF﹑ TpP含量明显升高,(FⅧ:C 167.52±51.46%VS 118.08±31.6%, vWF 236.91±81.79%VS 180.89±40.67% TpP 11.06±1.67μg/ml VS 8.77±2.3μg/ml)有显著性差异(P<0.05),血浆FIX:C无显著性差异。
4鳞癌﹑腺癌﹑小细胞癌患者与健康对照组比较血浆FⅧ:C﹑FIX:C﹑vWF:Ag﹑ TpP含量均有显著性差异,鳞癌﹑腺癌﹑小细胞癌三组间FⅧ:C﹑FIX:C﹑TpP含量无显著性差异。鳞癌组vWF:Ag最高,与腺癌组比较有显著性差异(250.63±95.3 VS195.11±59.76, P<0.05)。
5肺癌﹑卵巢癌患者手术前后血浆FⅧ:C﹑FIX:C﹑vWF:Ag﹑ TpP含量都明显高于对照组,有显著性差异(P<0.01),肺癌﹑卵巢癌患者手术后血浆FⅧ:C﹑FIX:C﹑ TpP x±s含量明显高于手术前,(FⅧ:C 234.7±64.7%VS 175.5±70.28%,FIX:C 194.4±42.98%VS 158.4±32.64%,TpP 13.31±2.64μg/ml VS 10.21±2.5μg/ml)有显著性差异(P<0.05),手术后vWF:Ag较手术前降低,无显著性差异。
结论
1肺癌﹑卵巢癌患者血浆FⅧ:C、FIX:C与vWF:Ag、TpP含量明显升高,提示肺癌﹑卵巢癌患者处于血栓前状态,易发生血栓,对评估肺癌﹑卵巢癌的预后、指导治疗有一定的价值。
2肺癌患者血浆FⅧ:C与vWF:Ag、TpP含量随肿瘤转移不断升高,说明肺癌患者血栓前状态与病情进展有密切关系,FⅧ:C、vWF:Ag、TpP含量升高对肺癌患者病情变化及预后有预测意义,可作为对肺癌血栓前状态的诊断和估计病情、判断预后及指导治疗较为敏感的指标。
3肺癌﹑卵巢癌患者手术后血栓前状态较手术前进一步加剧,提示对癌症患者手术后第七天进行预防性抗凝治疗是十分必要的。
Thrombosis is a common complication of malignancy and the second cause of death in cancer patients. The incidence rate of venous thrombosis of ovarian cancer and lung cancer were 10.6% and 4.4%.A series of pathology, laboratory and clinical research had shown that change in the blood coagulation, anticoagulation, fibrinolytic system is closely related to malignancy. We determined parameters such as activity of plasma coagulation factorⅧ(FⅧ:C)and activity of plasma coagulation factor IX(FIX:C), antigen contents of plasma von Willebrand factor (vWF:Ag) and plasma levels of thrombus precursor protein(TpP) in this experiment to detect changes of the four reflected prethrombotic status indicators in the course of lung cancer and ovarian cancer.
Objective
1. To investigate the changes of FⅧ:C and FIX:C, vWF:Ag and TpP levels in patients with pulmonary cancer and ovrian cancer and their correlation with stage and type of lung cancer and ovrian cancer.
2. To investigate the changes of FⅧ:C and FIX:C, vWF:Ag and TpP levels and their clinical significancy in patients with pulmonary cancer and ovrian cancer before and after surgery.
3. To provide a new target for the prevention,diagnosis and treatment of prethrombotic state in pulmonary cancer patients and ovrian cancer patients by study on FⅧ:C and FIX:C, vWF:Ag and TpP levels in patients with pulmonary cancer and ovrian cancer .
Methods
38 patients with pulmonary cancer and 11 patients with ovrian cancer were diagnosed according to pathology or cytology and enrolled in this study ,including 26 male and 23 female, average 61±8.9 years old .20 healthy individuals were taken as control, including 11 male and 9 female, average 57±8.2 years old . The three groups had no significant differences in age. According to TNM stage and clinical stage of lung cancer , 38 patients were divided into two groups : 13 cases in theⅠ～Ⅱstage pulmonary cancer , 25 cases in theⅢ～Ⅳstage of pulmonary cancer . The histologic type was squamous-cell carcinoma in 11 patients , adenocarcinoma in 21 patients and small cell lung cancer in 6 patients. 4ml peripheral blood was collected by sodium citrate (1:9) .Plasma was separated and FⅧ:C and FIX:C were tested by solidification on the Stago Campct automatic coagulometer . Plasma vWF:Ag and TpP levels were detected by enzyme-linked immunosorbent assay (ELISA).The patients who had had operation treatment were phlebotomized on the seventh day after surgery. 4ml peripheral blood was collected and anticoagulated by sodium citrate anticoagulation solution (1:9) ,dealing with the former.The data were shown by mean±standard, the results were compared by Independent-Samples T Test or one-way analysis of variance between groups and the results before and after surgery were compared by paired T Test.
Results
(1) The levels of plasma FⅧ:C , FIX:C , vWF:Ag and TpP in patients with pulmonary cancer were significantly higher than healthy controls respectively(FⅧ:C 150.61±50.06% VS 77.4±19.8%,FIX:C 143.45±27.41%VS 102.75±9.61%,vWF 217.74±74.84% VS 140.29±53.54%,TpP 10.14±2.07μg/ml VS 3.58±1.59μg/ml,all P<0.01)
(2) The levels of plasma FⅧ:C , FIX:C , vWF:Ag and TpP levels in patients with ovrian cancer were significantly higher than healthy controls respectively (FⅧ:C185.18±90.12 VS 77.4±19.8%, FIX:C 146±40.1 VS 102.75±9.61%,vWF 221.23±109.91 VS140.29±53.54%,TpP 10.1±1.7μg/ml VS3.58±1.59μg/ml,P<0.05)
(3) The levels of plasma FⅧ:C , FIX:C , vWF:Ag and TpP in theⅠ～Ⅱstage patients with pulmonaty cancer were significantly higher than healthy controls respectively,(P<0.05). The levels of plasma FⅧ:C, vWF:Ag and TpP in theⅢ～Ⅳstage patients with cancer were significantly higher than theⅠ～Ⅱstage patients with pulmonary cancer respectively,(FⅧ:C 167.52±51.46%VS 118.08±31.6%, vWF 236.91±81.79 % VS 180.89±40.67 % , TpP 11.06±1.67μg/ml VS 8.77±2.3μg/ml, P<0.05).Plasma FIX:C was not significantly differences between tow groups.
(4) Four trombosis-related markers were significantly higher among patients with squamous-cell carcinoma, patients with adenocarcinoma and small cell lung cancer than healthy controls,but plasma FⅧ:C﹑FIX:C, TpP levels were not significantly different among three groups.Plasma vWF:Ag was higher significantly in patients with squamous-cell carcinoma than patients with adenocarcinoma , (250.63±95.3 VS195.11±59.76, P<0.05).
(5)The levels of plasma FⅧ:C , FIX:C,vWF:Ag and TpP before and after surgery in patients with lung cancer and ovrian cancer are significantly higher than healthy controls respectively ,(P<0.01). Plasma FⅧ:C and FIX:C,TpP levels were significantly higher respectively after surgery in patients with lung cancer and ovrian cancer than before surgery .(FⅧ:C 234.7±64.7%VS 175.5±70.28%,FIX:C 194.4±42.98% VS 158.4±32.64%,TpP 13.31±2.64μg/ml VS 10.21±2.5μg/ml P<0.05). Plasma vWF:Ag was lower after surgery than before surgery. It was not significantly different after surgery and before surgery.
Conclusion
1. Increasing of plasma FⅧ:C, FIX:C, vWF:Ag and TpP levels in patients with lung cancer and ovrian cancer significantly suggested that these patients were in prethrombotic state and they be proned to thrombosis. It was a certain valuble in assessing prognosis and guide treatment of lung cancer and ovrian cancer.
2. Plasma FⅧ:C , vWF:Ag and TpP levels in patients with lung cancer continue to increase with tumor metastasis suggested that lung cancer patients with prethrombotic state is closely related to disease progression. Increasing of plasma FⅧ:C, vWF:Ag and TpP levels in lung cancer patients predicted change in condition and prognosis. They could be as more sensitive indicators which was used to diagnose for prethrombotic state, evaluate progress of the condition , determine prognosis and recommend treatment for lung cancer.
3. Lung cancer and ovrian cancer patients were in prethrombotic state after surgery than before surgery further. It suggested that preventive anticoagulant therapy is essential for cancer patients on the seventh day after surgery.
目的
1观察肺癌和卵巢癌患者中血浆FⅧ活性(FⅧ:C)、FIX活性(FIX:C)、vWF抗原含量(vWF:Ag)、TpP含量变化与肺癌分期分型及卵巢癌的相关性。
2探讨肺癌和卵巢癌患者手术前和手术后血浆FⅧ:C、FIX:C、vWF:Ag与TpP含量的变化及临床意义。
3通过对肺癌和卵巢癌患者血浆凝血因子FⅧ:C、FIX:C、vWF:Ag与TpP含量研究,为肺癌和卵巢癌患者血栓前状态的预防,诊断,治疗提供帮助。
方法
选择均经病理组织学或细胞学确诊38例肺癌和11例卵巢癌患者,男性26例,女性23例,平均年龄61±8.9岁,健康对照组20例,男性11例,女性9例,平均年龄57±8.2岁。三组间年龄无显著性差异。按照肺癌TNM分期和肺癌临床分期,肺癌Ⅰ～Ⅱ期病例13例,Ⅲ～Ⅳ期病例25例。病理分型:鳞癌11例,腺癌21例,小细胞癌6例。取外周静脉血4ml,注入含有柠檬酸钠抗凝液(1:9)试管内,提取血浆。用凝固法在Stago全自动凝血仪上测定血浆FⅧ活性、FIX活性,用ELISA(enzyme-linked immunosorbent assay)方法测定血浆VWF抗原含量、TpP含量。肿瘤组中接受手术治疗的患者于术后第7天采静脉血4ml,注入含有柠檬酸钠抗凝液(1:9)试管内,处理同前。统计学分析:所得的数据均用均数±标准差表示,组间比较采用独立样本t检验或单因素方差分析,手术前后样本采用配对t检验。
结果
1肺癌患者血浆FⅧ:C,FIX:C,vWF:Ag﹑TpP含量明显高于健康对照组(FⅧ:C 150.61±50.06% VS 77.4±19.8%,FIX:C 143.45±27.41%VS 102.75±9.61%,vWF 217.74±74.84% VS 140.29±53.54%,TpP 10.14±2.07μg/ml VS 3.58±1.59μg/ml),并存在显著差异(均P<0.01)。
2卵巢癌患者血浆FⅧ:C﹑FIX:C﹑vWF:Ag﹑TpP含量明显高于健康对照组(FⅧ:C185.18±90.12 VS 77.4±19.8%, FIX:C 146±40.1 VS 102.75±9.61%,vWF 221.23±109.91 VS140.29±53.54%,TpP 10.1±1.7μg/ml VS 3.58±1.59μg/ml),并存在显著差异( P<0.05)。
3肺癌Ⅰ～Ⅱ期患者血浆FⅧ:C,FIX:C,vWF:Ag﹑TpP含量明显高于健康对照组,有显著性差异,(P<0.05)肺癌Ⅲ～Ⅳ期与Ⅰ～Ⅱ期患者比较,血浆FⅧ:C﹑vWF﹑ TpP含量明显升高,(FⅧ:C 167.52±51.46%VS 118.08±31.6%, vWF 236.91±81.79%VS 180.89±40.67% TpP 11.06±1.67μg/ml VS 8.77±2.3μg/ml)有显著性差异(P<0.05),血浆FIX:C无显著性差异。
4鳞癌﹑腺癌﹑小细胞癌患者与健康对照组比较血浆FⅧ:C﹑FIX:C﹑vWF:Ag﹑ TpP含量均有显著性差异,鳞癌﹑腺癌﹑小细胞癌三组间FⅧ:C﹑FIX:C﹑TpP含量无显著性差异。鳞癌组vWF:Ag最高,与腺癌组比较有显著性差异(250.63±95.3 VS195.11±59.76, P<0.05)。
5肺癌﹑卵巢癌患者手术前后血浆FⅧ:C﹑FIX:C﹑vWF:Ag﹑ TpP含量都明显高于对照组,有显著性差异(P<0.01),肺癌﹑卵巢癌患者手术后血浆FⅧ:C﹑FIX:C﹑ TpP x±s含量明显高于手术前,(FⅧ:C 234.7±64.7%VS 175.5±70.28%,FIX:C 194.4±42.98%VS 158.4±32.64%,TpP 13.31±2.64μg/ml VS 10.21±2.5μg/ml)有显著性差异(P<0.05),手术后vWF:Ag较手术前降低,无显著性差异。
结论
1肺癌﹑卵巢癌患者血浆FⅧ:C、FIX:C与vWF:Ag、TpP含量明显升高,提示肺癌﹑卵巢癌患者处于血栓前状态,易发生血栓,对评估肺癌﹑卵巢癌的预后、指导治疗有一定的价值。
2肺癌患者血浆FⅧ:C与vWF:Ag、TpP含量随肿瘤转移不断升高,说明肺癌患者血栓前状态与病情进展有密切关系,FⅧ:C、vWF:Ag、TpP含量升高对肺癌患者病情变化及预后有预测意义,可作为对肺癌血栓前状态的诊断和估计病情、判断预后及指导治疗较为敏感的指标。
3肺癌﹑卵巢癌患者手术后血栓前状态较手术前进一步加剧,提示对癌症患者手术后第七天进行预防性抗凝治疗是十分必要的。
Thrombosis is a common complication of malignancy and the second cause of death in cancer patients. The incidence rate of venous thrombosis of ovarian cancer and lung cancer were 10.6% and 4.4%.A series of pathology, laboratory and clinical research had shown that change in the blood coagulation, anticoagulation, fibrinolytic system is closely related to malignancy. We determined parameters such as activity of plasma coagulation factorⅧ(FⅧ:C)and activity of plasma coagulation factor IX(FIX:C), antigen contents of plasma von Willebrand factor (vWF:Ag) and plasma levels of thrombus precursor protein(TpP) in this experiment to detect changes of the four reflected prethrombotic status indicators in the course of lung cancer and ovarian cancer.
Objective
1. To investigate the changes of FⅧ:C and FIX:C, vWF:Ag and TpP levels in patients with pulmonary cancer and ovrian cancer and their correlation with stage and type of lung cancer and ovrian cancer.
2. To investigate the changes of FⅧ:C and FIX:C, vWF:Ag and TpP levels and their clinical significancy in patients with pulmonary cancer and ovrian cancer before and after surgery.
3. To provide a new target for the prevention,diagnosis and treatment of prethrombotic state in pulmonary cancer patients and ovrian cancer patients by study on FⅧ:C and FIX:C, vWF:Ag and TpP levels in patients with pulmonary cancer and ovrian cancer .
Methods
38 patients with pulmonary cancer and 11 patients with ovrian cancer were diagnosed according to pathology or cytology and enrolled in this study ,including 26 male and 23 female, average 61±8.9 years old .20 healthy individuals were taken as control, including 11 male and 9 female, average 57±8.2 years old . The three groups had no significant differences in age. According to TNM stage and clinical stage of lung cancer , 38 patients were divided into two groups : 13 cases in theⅠ～Ⅱstage pulmonary cancer , 25 cases in theⅢ～Ⅳstage of pulmonary cancer . The histologic type was squamous-cell carcinoma in 11 patients , adenocarcinoma in 21 patients and small cell lung cancer in 6 patients. 4ml peripheral blood was collected by sodium citrate (1:9) .Plasma was separated and FⅧ:C and FIX:C were tested by solidification on the Stago Campct automatic coagulometer . Plasma vWF:Ag and TpP levels were detected by enzyme-linked immunosorbent assay (ELISA).The patients who had had operation treatment were phlebotomized on the seventh day after surgery. 4ml peripheral blood was collected and anticoagulated by sodium citrate anticoagulation solution (1:9) ,dealing with the former.The data were shown by mean±standard, the results were compared by Independent-Samples T Test or one-way analysis of variance between groups and the results before and after surgery were compared by paired T Test.
Results
(1) The levels of plasma FⅧ:C , FIX:C , vWF:Ag and TpP in patients with pulmonary cancer were significantly higher than healthy controls respectively(FⅧ:C 150.61±50.06% VS 77.4±19.8%,FIX:C 143.45±27.41%VS 102.75±9.61%,vWF 217.74±74.84% VS 140.29±53.54%,TpP 10.14±2.07μg/ml VS 3.58±1.59μg/ml,all P<0.01)
(2) The levels of plasma FⅧ:C , FIX:C , vWF:Ag and TpP levels in patients with ovrian cancer were significantly higher than healthy controls respectively (FⅧ:C185.18±90.12 VS 77.4±19.8%, FIX:C 146±40.1 VS 102.75±9.61%,vWF 221.23±109.91 VS140.29±53.54%,TpP 10.1±1.7μg/ml VS3.58±1.59μg/ml,P<0.05)
(3) The levels of plasma FⅧ:C , FIX:C , vWF:Ag and TpP in theⅠ～Ⅱstage patients with pulmonaty cancer were significantly higher than healthy controls respectively,(P<0.05). The levels of plasma FⅧ:C, vWF:Ag and TpP in theⅢ～Ⅳstage patients with cancer were significantly higher than theⅠ～Ⅱstage patients with pulmonary cancer respectively,(FⅧ:C 167.52±51.46%VS 118.08±31.6%, vWF 236.91±81.79 % VS 180.89±40.67 % , TpP 11.06±1.67μg/ml VS 8.77±2.3μg/ml, P<0.05).Plasma FIX:C was not significantly differences between tow groups.
(4) Four trombosis-related markers were significantly higher among patients with squamous-cell carcinoma, patients with adenocarcinoma and small cell lung cancer than healthy controls,but plasma FⅧ:C﹑FIX:C, TpP levels were not significantly different among three groups.Plasma vWF:Ag was higher significantly in patients with squamous-cell carcinoma than patients with adenocarcinoma , (250.63±95.3 VS195.11±59.76, P<0.05).
(5)The levels of plasma FⅧ:C , FIX:C,vWF:Ag and TpP before and after surgery in patients with lung cancer and ovrian cancer are significantly higher than healthy controls respectively ,(P<0.01). Plasma FⅧ:C and FIX:C,TpP levels were significantly higher respectively after surgery in patients with lung cancer and ovrian cancer than before surgery .(FⅧ:C 234.7±64.7%VS 175.5±70.28%,FIX:C 194.4±42.98% VS 158.4±32.64%,TpP 13.31±2.64μg/ml VS 10.21±2.5μg/ml P<0.05). Plasma vWF:Ag was lower after surgery than before surgery. It was not significantly different after surgery and before surgery.
Conclusion
1. Increasing of plasma FⅧ:C, FIX:C, vWF:Ag and TpP levels in patients with lung cancer and ovrian cancer significantly suggested that these patients were in prethrombotic state and they be proned to thrombosis. It was a certain valuble in assessing prognosis and guide treatment of lung cancer and ovrian cancer.
2. Plasma FⅧ:C , vWF:Ag and TpP levels in patients with lung cancer continue to increase with tumor metastasis suggested that lung cancer patients with prethrombotic state is closely related to disease progression. Increasing of plasma FⅧ:C, vWF:Ag and TpP levels in lung cancer patients predicted change in condition and prognosis. They could be as more sensitive indicators which was used to diagnose for prethrombotic state, evaluate progress of the condition , determine prognosis and recommend treatment for lung cancer.
3. Lung cancer and ovrian cancer patients were in prethrombotic state after surgery than before surgery further. It suggested that preventive anticoagulant therapy is essential for cancer patients on the seventh day after surgery.
引文
[1] Levine MN , Lee AY, Kakkar AK. Thrombosis and cancer.Am Soc Clin Oncol Educational Book , 2005 , 748.
[2] Blom JW, Doggen CJ , Osanto S , et al. Malignancies , prothrombotic mutations , and the risk of venous thrombosis. JAMA , 2005 , 293 (6)∶715.
[3] Goldhaber SZ, Tapson VF. DVT FREE Steering Committee. A prospective registry of 5 , 451 patients with ultrasound - con2 firmed deep vein thrombosis. Am J Cardiol , 2004 , 93 (2)∶259 .
[4] Thodiyil PA , Kakkar AK. Variation in relative risk of venous thromboembolism in different cancers. Thromb Haemost ,2002 , 87∶1076 .
[5] RoderikA Kraaijenhagen .High plasmal concentration of factorⅧc is a major factor for venous thrombosis.Thromb Haemost,2000,83:5-9 .
[6]欧阳秀莲,秦翠萍,闭雄杰.妇科恶性肿瘤术后下肢深静脉血栓形成及手术前后凝血和纤溶系统的变化.中国厂矿医学2007, 20(1):9-11.
[7]华佳叶,冯莹等.血液肿瘤患者中血管性血友病因子、二聚体、抗凝血酶检测的意义.血栓与止血, 2006, 12(3):123-125.
[8]郑长武,周志泳.血栓前体蛋白的研究进展.医学综述, 2007,(19): 1475-1477.
[9]储岳峰.血栓前体蛋白在诊断血栓形成性疾病中的应用.国外医学心血管疾病分册, 2005 ,32(5):299-302.
[10]魏文宁,杨锐,杨焰等.血栓前体蛋白检测的临床意义.中华内科杂志2004, 43(6): 49-51.
[11]陆再英,钟南山.内科学,第七版,北京:人民卫生出版社,2008: 122-126 .
[12]王鸿利.恶性肿瘤与血栓形成.肿瘤, 2008, 28(9:740-742.
[13] Paolo Prandoni, Anna Falanga .Cancer and venous thromboembolism Lancet Oncol. 2005; 6: 401–10 .
[14] Marcello De Cicco. The prothrombotic state in cancer:pathogenic mechanisms.Critical Reviews in Oncology/Hematology ,50 (2004): 187–196.
[15]刘泽霖,李家增.血栓性疾病的诊断和治疗.第二版,北京:人民卫生出版社,2006:97-102,133-140.
[16]汲森,包承鑫,崔娴维,等.血浆凝血因子Ⅷ增高与血栓形成.血栓与止血学,2001, 7(4):181-183.
[17]谢飞,王鸿利.凝血因子Ⅷ结构与功能关系的研究进展.国外医学临床生物化学与检验学分册,2005,26(12):932-935.
[18] Dent JA, Galbusera M, Ruggeri ZM. Heterogeneity of plasma von Willebrand factor multimers resulting from proteolysis of the constituent subunit. J Clin Invest, 1991;88:774-782.
[19] Anil K. Chauhan,Janka Kisucka .von Willebrand factor and factor VIII are independently required to form stable occlusive thrombi in injured veins . Blood, 2007,109:2424-2429.
[20]陈凯骏.血栓前体蛋白(TpP)与血栓形成相关性疾病的关系.血栓与止血,2003 ,9 (4) :176-178.
[21] Ursula Rauch, Silvio Antoniak. Association of tissue-factor upregulation in squamous-cell carcinoma of the lung with increased tissue factor in circulating blood .Lancet Oncol, 2005, 6: 254 .
[22] Salge U, Seitz R .Transition from suspension to adherent growth is accompanied by tissue factor expression and matrix metalloproteinase secretion in a small cell lung cancer cell line. J Cancer Res Clin Oncol, 2001 Feb,127(2):139-41.
[23] Liz Y. Han, Charles N,stl .Preoperative serum tissue factor levels are an independent prognostic factor in patients with ovarian carcinoma. Journal of Clinical Oncology , 2006 ,24(5): 755-761.
[24]闭雄杰,林发全.恶性肿瘤与血栓形成关系的研究进展.验医学与临床, 2007 ,4 (1O):979-980 .
[25] F. Guadagnia P. Ferronib,S. Basili et al.Correlation between tumor necrosis factor-alpha and D-dimer levels in non-small cell lung cancer patients .Lung Cancer ,(2004) ,44 : 303—310.
[26] Matanic D, Beg-Zec Z, Stojanovic D,et al.Cytokines in patients with lung cancer.Scand J Immunol, 2003,57:173—8.
[27] Szlosarek PW, Grimshaw MJ , Kulbe H ,et al. Expression and regulation of tumor necrosis factor alpha in normal and malignant ovarian epithelium .Mol Cancer Ther, 2006, Feb,5(2):382-90.
[28]陈文慧,张予辉.恶性肿瘤与血液系统.国际呼吸杂志,2007 , 27(8):588-590.
[29] R osendaal FR.High levels of factorⅧand venous thrombosis. Thromb Haemost,2000,83:1-2.
[30] Astrid van Hylckama Vlieg .High levels of factor IX increase the risk of venous thrombosis. BLOOD ,2000 ,95 (12):3678-3682 .
[31]关则兵,潘学谊,蔡小燕.蛋白Z及凝血因子在恶性实体瘤患者中的变化.血栓与止血, 2007, 13(3): 101-106 .
[32]商谊,潘学谊,丁彩屏,等.在恶性肿瘤患者中检测蛋白质Z的临床意义.癌症, 2005, 24 (9):1144-1147 .
[33] Mario Berger, Manuel Mattheisen, Bettina Kulle, et al. High factor VIII levels in venous thromboembolism show linkage to imprinted loci on chromosomes 5 and 11.Blood ,2005, 105: 638-644 .
[34] Mendolicchio GL, Ruggeri ZM. New perspectives on von Willebrand factor functions in hemostasis and thrombosis.Semin Hematol ,2005,42:5–14.
[35] Ruggeri ZM. Platelet and von Willebrand factor interactions at the vessel wall. Haand its relationship to metastasis. British Journal of Cancer, 1999, 79(3/4):472–47 .
[40] Wei-Shu Wang, Jen-Kou Lin, Tzu-Chen Lin,et al. Plasma von Willebrand factor level as a prognostic indicator of patients with metastatic colorectal carcinoma. World J Gastroenterol ,2005,11(14):2166-2170 .
[41]高维强,王兆钺,汪家敏.肿瘤患者血清血管性血友病因子裂解酶与可溶性尿激酶受体和胸腺素a1的检测和意义.中华检验医学杂志, 2004, 27 (7):411-414 .
[42] Ruggeri ZM. von Willebrand factor.J Clin Invest ,1997, 99: 559–64.
[43]魏文宁,郭涛,祝建芳.恶性肿瘤血栓前体蛋白水平改变的临床意义.中华内科学杂志, 2006 ,45 (12):1026.
[44] Hyun Kyung Kim . Plasma levels of D-dimer and soluble fibrin polymer in patients with hepatocellular carcinoma: a possible predictor of tumor thrombosis.Thrombosis Research, 109 (2003) :125–129 .
[45]丁毅鹏,冯保印.肺癌患者血浆凝血因子Ⅷ相关抗原及有关指标含量变化的研究中华结核和呼吸杂志. 1994 (17)15: 301-320 .
[46] Unsal E,AtalayF,AtikcanS, et al.Prognostic significance of hemostatic parameters in patients with lung cancer.;Respir Med,2004,98(2):93-98 .
[47]闭雄杰,欧阳秀莲.手术后血栓形成研究进展.右江民族医学院学报, 2006 (5):855-857.
[48] Piccioli A, Prandoni P, Ewenstein BM, Goldhaber SZ. Cancer and venous thromboembolism. Am Heart J, 1996,132:850–855.
[1] Le Treut YP, Hardwigsen J, Ananian P, et al. Resection of hepatocellular carcinoma with tumor thrombus in the major vasculature. A European case-control series.J Gastrointest Surg,2006, 10:855–862 .
[2] Blom JW, Doggen CJ , Osanto S , et al. Malignancies , prothrombotic mutations , and the risk of venous thrombosis. JAMA , 2005 , 293 (6)∶715 .
[3] Piccioli A, Prandoni P, Ewenstein BM, Goldhaber SZ. Cancer and venous thromboembolism. Am Heart J, 1996,132:850–855.
[4]侯明,刘新光.恶性肿瘤相关的血栓栓塞研究进展.医学新近展, 2007(,27):1594-1596.
[5] Wojtukiewicz MZ, Zacharski LR, Memoli VA, et al. Fibrinogenfibrin transformation in situ in renal cell carcinoma. Anticancer Res 1990,10:579–582.
[6] Koh SC, Khalil R, Lim FK, et al. The association between fibrinogen, von Willebrand Factor, antithrombin III, and D-dimer levels and survival outcome by 36 months from ovarian cancer. Clin Appl Thromb Hemost,2006, 12:3–8.
[7] Hau C. Kwaan Brian Vicuna Thrombosis and bleeding in cancer patients. Oncol Rev ,2007, 1:14–27 .
[8] Paolo Prandoni, Anna Falanga, Andrea Piccioli . Cancer and venous thromboembolism . Lancet Oncol, 2005, 6: 401–10.
[9] Marcello De Cicco. The prothrombotic state in cancer:pathogenic mechanisms .Critical Reviews in Oncology/Hematology, 2004, 50 187–196 .
[10] Grignani G, Maiolo A. Cytokines and hemostasis. Haematologica,2000, 85: 967–72.
[11]闭雄杰,林发全.性肿瘤与血栓形成关系的研究进展.验医学与临床,2007, 4 (1O):979-980 .
[12] H. R. BULLER, F. F. VAN DOORMAAL, G. L. VAN SLUIS ,et al. Cancer and thrombosis: from molecular mechanisms to clinical presentations. J Thromb Haemost, 2007, 5 (Suppl. 1): 246–54.
[13] Kwaan HC . The plasminogenplasmin system in malignancy. Cancer Metastasis Rev,1992,11:291–311.
[14] Hajjar KA. Fibrinolysis revisited: new insights into the pathobiology of cancer. Vessels, 1996,2:9–16.
[15] De Cicco M, Matovic M, Balestrieri L, et al. Antithrombin III deficiencyas a risk factor for catheter-related central vein thrombosis in cancer patients. Thromb Res, 1995,78:127–37.
[16] Rodeghiero F, Mannucci PM, Vigano S, et al. Liver dysfunction rather than intravascular coagulation as the main cause of low protein C and antithrombin III in acute leukemia. Blood, 1984,63:965–9 .
[17] Heit JA, Silverstein MD, Mohr DN, et al. Risk factors for deep vein thrombosis and pulmonary embolism, a population-based case-control study. Arch Intern Med, 2000,160:809– 15.
[18] Goodnough,StatioA , ManniA . Increased in cancer patients undergoing chemotherapy. Thromb Haemost, 1997, 18:133-6 .
[19]欧阳秀莲,秦翠萍,闭雄杰.妇科恶性肿瘤术后下肢深静脉血栓形成及手术前后凝血和纤溶系统的变化.中国厂矿医学2007, 20(1):9-11.
[20]闭雄杰,欧阳秀莲.手术后血栓形成研究进展.右江民族医学院学报,2006 ,(5):855-857.
[21] Piccioli A, Prandoni P, Ewenstein BM, Goldhaber SZ. Cancer and venous thromboembolism. Am Heart J, 1996,132:850–855.
[22]胡豫,王华芳.肿瘤并发血栓形成机制及治疗.中国实用内科杂志, 2007 , 27(20):1591-1593 .
[23] Kovacs MJ, Levine MN, Keeney M, et al. Anti-Xa effect of a low molecular weight heparin (dalteparin) does not accumulate in extended duration therapy for venous thromboembolism in cancer patients. Thromb Haemost, 2005,93:1185–1188.
[24] Lee AY, Levine MN, Baker RI, et al. Lowmolecular- weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med,2003, 349:146–153.
[25] Buller HR, Agnelli G, Hull RD, et al. Antithrombotic therapy for venousthromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest, 2004,126:401S–428S.
[26] Tallman MS, Kwaan HC . Intravascular clotting activation and bleeding in patients with hematologic malignancies. Rev Clin Exp Hematol, 2004,8:E1.
[27] Wolfgang Korte. Cancer and thrombosis: an increasingly important association. Support Care Cancer, 2008, 16:223–228.
[28]常树建.癌症与血栓性疾病.医学综述, 2006 , 10:603-605.
[2] Blom JW, Doggen CJ , Osanto S , et al. Malignancies , prothrombotic mutations , and the risk of venous thrombosis. JAMA , 2005 , 293 (6)∶715.
[3] Goldhaber SZ, Tapson VF. DVT FREE Steering Committee. A prospective registry of 5 , 451 patients with ultrasound - con2 firmed deep vein thrombosis. Am J Cardiol , 2004 , 93 (2)∶259 .
[4] Thodiyil PA , Kakkar AK. Variation in relative risk of venous thromboembolism in different cancers. Thromb Haemost ,2002 , 87∶1076 .
[5] RoderikA Kraaijenhagen .High plasmal concentration of factorⅧc is a major factor for venous thrombosis.Thromb Haemost,2000,83:5-9 .
[6]欧阳秀莲,秦翠萍,闭雄杰.妇科恶性肿瘤术后下肢深静脉血栓形成及手术前后凝血和纤溶系统的变化.中国厂矿医学2007, 20(1):9-11.
[7]华佳叶,冯莹等.血液肿瘤患者中血管性血友病因子、二聚体、抗凝血酶检测的意义.血栓与止血, 2006, 12(3):123-125.
[8]郑长武,周志泳.血栓前体蛋白的研究进展.医学综述, 2007,(19): 1475-1477.
[9]储岳峰.血栓前体蛋白在诊断血栓形成性疾病中的应用.国外医学心血管疾病分册, 2005 ,32(5):299-302.
[10]魏文宁,杨锐,杨焰等.血栓前体蛋白检测的临床意义.中华内科杂志2004, 43(6): 49-51.
[11]陆再英,钟南山.内科学,第七版,北京:人民卫生出版社,2008: 122-126 .
[12]王鸿利.恶性肿瘤与血栓形成.肿瘤, 2008, 28(9:740-742.
[13] Paolo Prandoni, Anna Falanga .Cancer and venous thromboembolism Lancet Oncol. 2005; 6: 401–10 .
[14] Marcello De Cicco. The prothrombotic state in cancer:pathogenic mechanisms.Critical Reviews in Oncology/Hematology ,50 (2004): 187–196.
[15]刘泽霖,李家增.血栓性疾病的诊断和治疗.第二版,北京:人民卫生出版社,2006:97-102,133-140.
[16]汲森,包承鑫,崔娴维,等.血浆凝血因子Ⅷ增高与血栓形成.血栓与止血学,2001, 7(4):181-183.
[17]谢飞,王鸿利.凝血因子Ⅷ结构与功能关系的研究进展.国外医学临床生物化学与检验学分册,2005,26(12):932-935.
[18] Dent JA, Galbusera M, Ruggeri ZM. Heterogeneity of plasma von Willebrand factor multimers resulting from proteolysis of the constituent subunit. J Clin Invest, 1991;88:774-782.
[19] Anil K. Chauhan,Janka Kisucka .von Willebrand factor and factor VIII are independently required to form stable occlusive thrombi in injured veins . Blood, 2007,109:2424-2429.
[20]陈凯骏.血栓前体蛋白(TpP)与血栓形成相关性疾病的关系.血栓与止血,2003 ,9 (4) :176-178.
[21] Ursula Rauch, Silvio Antoniak. Association of tissue-factor upregulation in squamous-cell carcinoma of the lung with increased tissue factor in circulating blood .Lancet Oncol, 2005, 6: 254 .
[22] Salge U, Seitz R .Transition from suspension to adherent growth is accompanied by tissue factor expression and matrix metalloproteinase secretion in a small cell lung cancer cell line. J Cancer Res Clin Oncol, 2001 Feb,127(2):139-41.
[23] Liz Y. Han, Charles N,stl .Preoperative serum tissue factor levels are an independent prognostic factor in patients with ovarian carcinoma. Journal of Clinical Oncology , 2006 ,24(5): 755-761.
[24]闭雄杰,林发全.恶性肿瘤与血栓形成关系的研究进展.验医学与临床, 2007 ,4 (1O):979-980 .
[25] F. Guadagnia P. Ferronib,S. Basili et al.Correlation between tumor necrosis factor-alpha and D-dimer levels in non-small cell lung cancer patients .Lung Cancer ,(2004) ,44 : 303—310.
[26] Matanic D, Beg-Zec Z, Stojanovic D,et al.Cytokines in patients with lung cancer.Scand J Immunol, 2003,57:173—8.
[27] Szlosarek PW, Grimshaw MJ , Kulbe H ,et al. Expression and regulation of tumor necrosis factor alpha in normal and malignant ovarian epithelium .Mol Cancer Ther, 2006, Feb,5(2):382-90.
[28]陈文慧,张予辉.恶性肿瘤与血液系统.国际呼吸杂志,2007 , 27(8):588-590.
[29] R osendaal FR.High levels of factorⅧand venous thrombosis. Thromb Haemost,2000,83:1-2.
[30] Astrid van Hylckama Vlieg .High levels of factor IX increase the risk of venous thrombosis. BLOOD ,2000 ,95 (12):3678-3682 .
[31]关则兵,潘学谊,蔡小燕.蛋白Z及凝血因子在恶性实体瘤患者中的变化.血栓与止血, 2007, 13(3): 101-106 .
[32]商谊,潘学谊,丁彩屏,等.在恶性肿瘤患者中检测蛋白质Z的临床意义.癌症, 2005, 24 (9):1144-1147 .
[33] Mario Berger, Manuel Mattheisen, Bettina Kulle, et al. High factor VIII levels in venous thromboembolism show linkage to imprinted loci on chromosomes 5 and 11.Blood ,2005, 105: 638-644 .
[34] Mendolicchio GL, Ruggeri ZM. New perspectives on von Willebrand factor functions in hemostasis and thrombosis.Semin Hematol ,2005,42:5–14.
[35] Ruggeri ZM. Platelet and von Willebrand factor interactions at the vessel wall. Haand its relationship to metastasis. British Journal of Cancer, 1999, 79(3/4):472–47 .
[40] Wei-Shu Wang, Jen-Kou Lin, Tzu-Chen Lin,et al. Plasma von Willebrand factor level as a prognostic indicator of patients with metastatic colorectal carcinoma. World J Gastroenterol ,2005,11(14):2166-2170 .
[41]高维强,王兆钺,汪家敏.肿瘤患者血清血管性血友病因子裂解酶与可溶性尿激酶受体和胸腺素a1的检测和意义.中华检验医学杂志, 2004, 27 (7):411-414 .
[42] Ruggeri ZM. von Willebrand factor.J Clin Invest ,1997, 99: 559–64.
[43]魏文宁,郭涛,祝建芳.恶性肿瘤血栓前体蛋白水平改变的临床意义.中华内科学杂志, 2006 ,45 (12):1026.
[44] Hyun Kyung Kim . Plasma levels of D-dimer and soluble fibrin polymer in patients with hepatocellular carcinoma: a possible predictor of tumor thrombosis.Thrombosis Research, 109 (2003) :125–129 .
[45]丁毅鹏,冯保印.肺癌患者血浆凝血因子Ⅷ相关抗原及有关指标含量变化的研究中华结核和呼吸杂志. 1994 (17)15: 301-320 .
[46] Unsal E,AtalayF,AtikcanS, et al.Prognostic significance of hemostatic parameters in patients with lung cancer.;Respir Med,2004,98(2):93-98 .
[47]闭雄杰,欧阳秀莲.手术后血栓形成研究进展.右江民族医学院学报, 2006 (5):855-857.
[48] Piccioli A, Prandoni P, Ewenstein BM, Goldhaber SZ. Cancer and venous thromboembolism. Am Heart J, 1996,132:850–855.
[1] Le Treut YP, Hardwigsen J, Ananian P, et al. Resection of hepatocellular carcinoma with tumor thrombus in the major vasculature. A European case-control series.J Gastrointest Surg,2006, 10:855–862 .
[2] Blom JW, Doggen CJ , Osanto S , et al. Malignancies , prothrombotic mutations , and the risk of venous thrombosis. JAMA , 2005 , 293 (6)∶715 .
[3] Piccioli A, Prandoni P, Ewenstein BM, Goldhaber SZ. Cancer and venous thromboembolism. Am Heart J, 1996,132:850–855.
[4]侯明,刘新光.恶性肿瘤相关的血栓栓塞研究进展.医学新近展, 2007(,27):1594-1596.
[5] Wojtukiewicz MZ, Zacharski LR, Memoli VA, et al. Fibrinogenfibrin transformation in situ in renal cell carcinoma. Anticancer Res 1990,10:579–582.
[6] Koh SC, Khalil R, Lim FK, et al. The association between fibrinogen, von Willebrand Factor, antithrombin III, and D-dimer levels and survival outcome by 36 months from ovarian cancer. Clin Appl Thromb Hemost,2006, 12:3–8.
[7] Hau C. Kwaan Brian Vicuna Thrombosis and bleeding in cancer patients. Oncol Rev ,2007, 1:14–27 .
[8] Paolo Prandoni, Anna Falanga, Andrea Piccioli . Cancer and venous thromboembolism . Lancet Oncol, 2005, 6: 401–10.
[9] Marcello De Cicco. The prothrombotic state in cancer:pathogenic mechanisms .Critical Reviews in Oncology/Hematology, 2004, 50 187–196 .
[10] Grignani G, Maiolo A. Cytokines and hemostasis. Haematologica,2000, 85: 967–72.
[11]闭雄杰,林发全.性肿瘤与血栓形成关系的研究进展.验医学与临床,2007, 4 (1O):979-980 .
[12] H. R. BULLER, F. F. VAN DOORMAAL, G. L. VAN SLUIS ,et al. Cancer and thrombosis: from molecular mechanisms to clinical presentations. J Thromb Haemost, 2007, 5 (Suppl. 1): 246–54.
[13] Kwaan HC . The plasminogenplasmin system in malignancy. Cancer Metastasis Rev,1992,11:291–311.
[14] Hajjar KA. Fibrinolysis revisited: new insights into the pathobiology of cancer. Vessels, 1996,2:9–16.
[15] De Cicco M, Matovic M, Balestrieri L, et al. Antithrombin III deficiencyas a risk factor for catheter-related central vein thrombosis in cancer patients. Thromb Res, 1995,78:127–37.
[16] Rodeghiero F, Mannucci PM, Vigano S, et al. Liver dysfunction rather than intravascular coagulation as the main cause of low protein C and antithrombin III in acute leukemia. Blood, 1984,63:965–9 .
[17] Heit JA, Silverstein MD, Mohr DN, et al. Risk factors for deep vein thrombosis and pulmonary embolism, a population-based case-control study. Arch Intern Med, 2000,160:809– 15.
[18] Goodnough,StatioA , ManniA . Increased in cancer patients undergoing chemotherapy. Thromb Haemost, 1997, 18:133-6 .
[19]欧阳秀莲,秦翠萍,闭雄杰.妇科恶性肿瘤术后下肢深静脉血栓形成及手术前后凝血和纤溶系统的变化.中国厂矿医学2007, 20(1):9-11.
[20]闭雄杰,欧阳秀莲.手术后血栓形成研究进展.右江民族医学院学报,2006 ,(5):855-857.
[21] Piccioli A, Prandoni P, Ewenstein BM, Goldhaber SZ. Cancer and venous thromboembolism. Am Heart J, 1996,132:850–855.
[22]胡豫,王华芳.肿瘤并发血栓形成机制及治疗.中国实用内科杂志, 2007 , 27(20):1591-1593 .
[23] Kovacs MJ, Levine MN, Keeney M, et al. Anti-Xa effect of a low molecular weight heparin (dalteparin) does not accumulate in extended duration therapy for venous thromboembolism in cancer patients. Thromb Haemost, 2005,93:1185–1188.
[24] Lee AY, Levine MN, Baker RI, et al. Lowmolecular- weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med,2003, 349:146–153.
[25] Buller HR, Agnelli G, Hull RD, et al. Antithrombotic therapy for venousthromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest, 2004,126:401S–428S.
[26] Tallman MS, Kwaan HC . Intravascular clotting activation and bleeding in patients with hematologic malignancies. Rev Clin Exp Hematol, 2004,8:E1.
[27] Wolfgang Korte. Cancer and thrombosis: an increasingly important association. Support Care Cancer, 2008, 16:223–228.
[28]常树建.癌症与血栓性疾病.医学综述, 2006 , 10:603-605.