Please wait a minute...
浙江大学学报（医学版）
浙江大学学报（医学版）  2020, Vol. 49 Issue (6): 772-778    DOI: 10.3785/j.issn.1008-9292.2020.12.13
综述     
组织因子与肿瘤患者静脉血栓栓塞
朱慧琦(),应可净*()
浙江大学医学院附属邵逸夫医院呼吸内科 国家呼吸疾病区域医疗中心, 浙江 杭州 310016
Tissue factors and venous thromboembolism in cancer patients
ZHU Huiqi(),YING Kejing*()
Department of Respiratory Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, National Regional Medical Center for Respiratory Diseases, Hangzhou 310016, China
 全文: PDF(1030 KB)   HTML( 22 )
摘要：

恶性肿瘤是静脉血栓栓塞（VTE）的重要获得性危险因素之一。组织因子作为体内凝血因子Ⅶ和活化形式的凝血因子Ⅶa的跨膜受体，是机体外源性凝血过程的主要起始物。肿瘤细胞表达释放的组织因子阳性微粒进入循环参与介导手术治疗和肿瘤远处转移患者的血栓形成；化疗后组织因子促凝活性增强导致很多肿瘤患者接受化疗后更容易发生血栓栓塞性疾病。在胰腺癌、结直肠癌和卵巢癌等肿瘤中，组织因子还可以用于预测患者VTE风险。本文总结了近年来组织因子在不同治疗阶段的肿瘤患者VTE中的作用，进一步明确组织因子与肿瘤患者VTE风险之间的关系。
关键词： 静脉血栓栓塞;  组织因子;  肿瘤治疗;  肿瘤转移;  风险预测;  综述    
Abstract:

Malignant tumor is one of the important acquired risk factors of venous thromboembolism (VTE). As the transmembrane receptor of coagulation factor Ⅶ and activated coagulation factor Ⅶa in vivo, tissue factor is the main initiator of exogenous coagulation. Tissue factor positive particles expressed and released by tumor cells enter the circulation and mediate thrombosis in patients with surgical treatment and distant tumor metastasis; the enhanced procoagulant activity of tissue factor after chemotherapy makes many cancer patients more likely to develop thromboembolic disease. Tissue factors can also be used to predict the risk of VTE in patients with pancreatic cancer, colorectal cancer and ovarian cancer.This article summarizes the role of tissue factor in VTE of cancer patients at different treatment stages, and further clarifies the relationship between tissue factor and the risk of VTE in cancer patients.
Key words: Venous thromboembolism    Tissue factors    Tumor therapy    Neoplasm metastasis    Prediction    Review
收稿日期: 2020-07-10 出版日期: 2021-01-14
CLC:  R364.1+5  
基金资助: 国家自然科学基金(81970049)
通讯作者: 应可净     E-mail: 21818343@zju.edu.cn;3197061@zju.edu.cn
作者简介: 朱慧琦(1994-), 女, 硕士研究生, 住院医师, 主要从事肺血管疾病研究; E-mail:21818343@zju.edu.cn; https://orcid.org/0000-0002-2108-6937
服务　　
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章　　
朱慧琦
应可净

引用本文:

朱慧琦,应可净. 组织因子与肿瘤患者静脉血栓栓塞[J]. 浙江大学学报（医学版）, 2020, 49(6): 772-778.

ZHU Huiqi,YING Kejing. Tissue factors and venous thromboembolism in cancer patients. J Zhejiang Univ (Med Sci), 2020, 49(6): 772-778.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2020.12.13    或    http://www.zjujournals.com/med/CN/Y2020/V49/I6/772

1 PABINGER I , THALER J , AY C . Biomarkers for prediction of venous thromboembolism in cancer[J]. Blood, 2013, 122 (12): 2011- 2018
doi: 10.1182/blood-2013-04-460147
2 TIMP J F , BRAEKKAN S K , VERSTEEG H H et al. Epidemiology of cancer-associated venous thrombosis[J]. Blood, 2013, 122 (10): 1712- 1723
doi: 10.1182/blood-2013-04-460121
3 FALANGA A , PANOVA-NOEVA M , RUSSO L . Procoagulant mechanisms in tumour cells[J]. Best Pract Res Clin Haematol, 2009, 22 (1): 49- 60
doi: 10.1016/j.beha.2008.12.009
4 FALANGA A , MARCHETTI M , VIGNOLI A . Coagulation and cancer: biological and clinical aspects[J]. J Thromb Haemost, 2013, 11 (2): 223- 233
doi: 10.1111/jth.12075
5 EDWARDS R L , MORGAN D L , RICKLES F R . Animal tumor procoagulants: registry of the Subcommittee on Haemostasis and Malignancy of the Scientific and Standardization Committee, International Society of Thrombosis and Haemostasis[J]. Thromb Haemost, 1990, 63 (1): 133- 138
doi: 10.1055/s-0038-1645699
6 MACKMAN N , MORRISSEY J H , FOWLER B et al. Complete sequence of the human tissue factor gene, a highly regulated cellular receptor that initiates the coagulation protease cascade[J]. Biochemistry, 1989, 28 (4): 1755- 1762
doi: 10.1021/bi00430a050
7 ZAHRA S , ANDERSON J A , STIRLING D et al. Microparticles, malignancy and thrombosis[J]. Br J Haematol, 2011, 152 (6): 688- 700
doi: 10.1111/j.1365-2141.2010.08452.x
8 KOMIYAMA Y , PEDERSEN A H , KISIEL W . Proteolytic activation of human factors Ⅸ and Ⅹ by recombinant human factor Ⅶa: effects of calcium, phospholipids, and tissue factor[J]. Biochemistry, 1990, 29 (40): 9418- 9425
doi: 10.1021/bi00492a016
9 ZWICKER J I , LIEBMAN H A , NEUBERG D et al. Tumor-derived tissue factor-bearing microparticles are associated with venous thromboembolic events in malignancy[J]. Clin Cancer Res, 2009, 15 (22): 6830- 6840
doi: 10.1158/1078-0432.CCR-09-0371
10 DRAKE T A , MORRISSEY J H , EDGINGTON T S . Selective cellular expression of tissue factor in human tissues. Implications for disorders of hemostasis and thrombosis[J]. AM J PATHOL, 1989, 134 (5): 1087- 1097
11 FLECK R A , RAO L V , RAPAPORT S I et al. Localization of human tissue factor antigen by immunostaining with monospecific, polyclonal anti-human tissue factor antibody[J]. Thromb Res, 1990, 59 (2): 421- 437
doi: 10.1016/0049-3848(90)90148-6
12 OTT I . Soluble tissue factor emerges from inflammation[J]. Circ Res, 2005, 96 (12): 1217- 1218
doi: 10.1161/01.RES.0000172745.09928.87
13 FONSECA R , CESARMAN-MAUS G , BRAGGIO E . Personalizing the use of circulating microparticle-associated tissue factor as a biomarker for recurrent thrombosis in patients with cancer[J]. J Clin Oncol, 2017, 35 (19): 2217- 2218
doi: 10.1200/JCO.2017.72.5341
14 MANLY D A , BOLES J , MACKMAN N . Role of tissue factor in venous thrombosis[J]. Annu Rev Physiol, 2011, 73:515- 525
doi: 10.1146/annurev-physiol-042210-121137
15 DVORAK H F , NAGY J A , DVORAK J T et al. Identification and characterization of the blood vessels of solid tumors that are leaky to circulating macromolecules[J]. Am J Pathol, 1988, 133 (1): 95- 109
16 AUWERDA J J , YUANA Y , OSANTO S et al. Microparticle-associated tissue factor activity and venous thrombosis in multiple myeloma[J]. Thromb Haemost, 2011, 105 (1): 14- 20
doi: 10.1160/TH10-03-0187
17 WANG J G , GEDDINGS J E , ALEMAN M M et al. Tumor-derived tissue factor activates coagulation and enhances thrombosis in a mouse xenograft model of human pancreatic cancer[J]. Blood, 2012, 119 (23): 5543- 5552
doi: 10.1182/blood-2012-01-402156
18 EDGINGTON T S , MACKMAN N , BRAND K et al. The structural biology of expression and function of tissue factor[J]. Thromb Haemost, 1991, 66 (1): 67- 79
doi: 10.1055/s-0038-1646375
19 PEPPELENBOSCH M P , VERSTEEG H H . Cell biology of tissue factor, an unusual member of the cytokine receptor family[J]. Trends Cardiovasc Med, 2001, 11 (8): 335- 339
doi: 10.1016/s1050-1738(01)00137-2
20 GORDON S G , MIELICKI W P . Cancer procoagulant: a factor X activator, tumor marker and growth factor from malignant tissue[J]. Blood Coagul Fibrinolysis, 1997, 8 (2): 73- 86
doi: 10.1097/00001721-199703000-00001
21 WOOD K E . Major pulmonary embolism: review of a pathophysiologic approach to the golden hour of hemodynamically significant pulmonary embolism[J]. Chest, 2002, 121 (3): 877- 905
doi: 10.1378/chest.121.3.877
22 BATTISTINI B . Modulation and roles of the endothelins in the pathophysiology of pulmonary embolism[J]. Can J Physiol Pharmacol, 2003, 81 (6): 555- 569
doi: 10.1139/y03-017
23 LAWSON C A , YAN S D , YAN S F et al. Monocytes and tissue factor promote thrombosis in a murine model of oxygen deprivation[J]. J Clin Invest, 1997, 99 (7): 1729- 1738
doi: 10.1172/JCI119337
24 WOEI-A-JIN F J , TESSELAAR M E , GARCIA RODRIGUEZ P et al. Tissue factor-bearing microparticles and CA19.9: two players in pancreatic cancer-associated thrombosis?[J]. Br J Cancer, 2016, 115 (3): 332- 338
doi: 10.1038/bjc.2016.170
25 AHAMED J , VERSTEEG H H , KERVER M et al. Disulfide isomerization switches tissue factor from coagulation to cell signaling[J]. Proc Natl Acad Sci U S A, 2006, 103 (38): 13932- 13937
doi: 10.1073/pnas.0606411103
26 PRANDONI P . Antithrombotic strategies in patients with cancer[J]. Thromb Haemost, 1997, 78 (1): 141- 144
doi: 10.1055/s-0038-1657517
27 ERNOFSSON M , THELIN S , SIEGBAHN A . Monocyte tissue factor expression, cell activation, and thrombin formation during cardiopulmonary bypass: a clinical study[J]. J Thoracic Cardiovas Surg, 1997, 113 (3): 576- 584
doi: 10.1016/S0022-5223(97)70373-8
28 CHUNG J , TABUCHI N , KOYAMA T . The increase in tissue factor-bearing leukocytes after off-pump coronary artery bypass surgery[J]. Thromb Haemost, 2008, 100 (5): 952- 954
doi: 10.1160/TH08-06-0349
29 DE MARTINO R R , GOODNEY P P , SPANGLER E L et al. Variation in thromboembolic complications among patients undergoing commonly performed cancer operations[J]. J Vasc Surg, 2012, 55 (4): 1035- 1040.e4
doi: 10.1016/j.jvs.2011.10.129
30 ALBRECHT S , MVLLER S , SIEGERT G et al. Plasma concentration of tissue factor and factor Ⅶ in patients after abdominal surgery[J]. Thromb Res, 1995, 77 (6): 557- 562
doi: 10.1016/0049-3848(95)00030-5
31 MERKOW R P , BILIMORIA K Y , MCCARTER M D et al. Post-discharge venous thromboembolism after cancer surgery: extending the case for extended prophylaxis[J]. Ann Surg, 2011, 254 (1): 131- 137
doi: 10.1097/SLA.0b013e31821b98da
32 HEIT J A , SILVERSTEIN M D , MOHR D N et al. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study[J]. Arch Intern Med, 2000, 160 (6): 809- 815
doi: 10.1001/archinte.160.6.809
33 GRACE R F , DAHLBERG S E , NEUBERG D et al. The frequency and management of asparaginase-related thrombosis in paediatric and adult patients with acute lymphoblastic leukaemia treated on Dana-Farber Cancer Institute consortium protocols[J]. Br J Haematol, 2011, 152 (4): 452- 459
doi: 10.1111/j.1365-2141.2010.08524.x
34 AMIR E , SERUGA B , NIRAULA S et al. Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis[J]. J Natl Cancer Inst, 2011, 103 (17): 1299- 1309
doi: 10.1093/jnci/djr242
35 OPPELT P , BETBADAL A , NAYAK L . Approach to chemotherapy-associated thrombosis[J]. Vasc Med, 2015, 20 (2): 153- 161
doi: 10.1177/1358863X14568705
36 SENG S , LIU Z , CHIU S K et al. Risk of venous thromboembolism in patients with cancer treated with Cisplatin: a systematic review and meta-analysis[J]. J Clin Oncol, 2012, 30 (35): 4416- 4426
doi: 10.1200/JCO.2012.42.4358
37 FALANGA A , MARCHETTI M . Anticancer treatment and thrombosis[J]. Thromb Res, 2012, 129 (3): 353- 359
doi: 10.1016/j.thromres.2011.10.025
38 BACH R R , MOLDOW C F . Mechanism of tissue factor activation on HL-60 cells[J]. Blood, 1997, 89 (9): 3270- 3276
doi: 10.1182/blood.V89.9.3270
39 LYSOV Z , SWYSTUN L L , KURUVILLA S et al. Lung cancer chemotherapy agents increase procoagulant activity via protein disulfide isomerase-dependent tissue factor decryption[J]. Blood Coagul Fibrinolysis, 2015, 26 (1): 36- 45
doi: 10.1097/MBC.0000000000000145
40 JACOBSEN C , OECHSLE K , HAUSCHILD J et al. Regulation of tissue factor in NT2 germ cell tumor cells by cisplatin chemotherapy[J]. Thromb Res, 2015, 136 (3): 673- 681
doi: 10.1016/j.thromres.2015.07.002
41 BILLROTH T . General surgical pathology and therapy. Guidance for students and physicians. Lecture[J]. Khirurgiia (Mosk), 1991, (10): 136- 143
42 ELIZONDO P , FOGELSON A L . A mathematical model of venous thrombosis initiation[J]. Biophys J, 2016, 111 (12): 2722- 2734
doi: 10.1016/j.bpj.2016.10.030
43 FAILLE D , BOURRIENNE M C , DE RAUCOURT E et al. Biomarkers for the risk of thrombosis in pancreatic adenocarcinoma are related to cancer process[J]. Oncotarget, 2018, 9 (41): 26453- 26465
doi: 10.18632/oncotarget.25458
44 RONDON A , KROONE C , KAPTEIJN M Y et al. Role of tissue factor in tumor progression and cancer-associated thrombosis[J]. Semin Thromb Hemost, 2019, 45 (4): 396- 412
doi: 10.1055/s-0039-1687895
45 TSENG J C , CHANG L C , JIANG B Y et al. Elevated circulating levels of tissue factor-positive microvesicles are associated with distant metastasis in lung cancer[J]. J Cancer Res Clin Oncol, 2014, 140 (1): 61- 67
doi: 10.1007/s00432-013-1544-8
46 KHORANA A A , FRANCIS C W , MENZIES K E et al. Plasma tissue factor may be predictive of venous thromboembolism in pancreatic cancer[J]. J Thromb Haemost, 2008, 6 (11): 1983- 1985
doi: 10.1111/j.1538-7836.2008.03156.x
47 TESSELAAR M E , ROMIJN F P , VAN DER LINDEN I K et al. Microparticle-associated tissue factor activity in cancer patients with and without thrombosis[J]. J Thromb Haemost, 2009, 7 (8): 1421- 1423
doi: 10.1111/j.1538-7836.2009.03504.x
48 KHORANA A A , AHRENDT S A , RYAN C K et al. Tissue factor expression, angiogenesis, and thrombosis in pancreatic cancer[J]. Clin Cancer Res, 2007, 13 (10): 2870- 2875
doi: 10.1158/1078-0432.CCR-06-2351
49 HRON G , KOLLARS M , WEBER H et al. Tissue factor-positive microparticles: cellular origin and association with coagulation activation in patients with colorectal cancer[J]. Thromb Haemost, 2007, 97 (1): 119- 123
doi: 10.1160/TH06-03-0141
50 AY C , VORMITTAG R , DUNKLER D et al. D-dimer and prothrombin fragment 1+2 predict venous thromboembolism in patients with cancer: results from the Vienna Cancer and Thrombosis Study[J]. J Clin Oncol, 2009, 27 (25): 4124- 4129
doi: 10.1200/JCO.2008.21.7752
51 UNO K , HOMMA S , SATOH T et al. Tissue factor expression as a possible determinant of thromboembolism in ovarian cancer[J]. Br J Cancer, 2007, 96 (2): 290- 295
doi: 10.1038/sj.bjc.6603552
52 GEZELIUS E , FLOU KRISTENSEN A , BENDAHL P O et al. Coagulation biomarkers and prediction of venous thromboembolism and survival in small cell lung cancer: a sub-study of RASTEN - a randomized trial with low molecular weight heparin[J]. PLoS One, 2018, 13 (11): e0207387
doi: 10.1371/journal.pone.0207387
53 ZUCCHELLA M , PACCHIARINI L , TACCONI F et al. Different expression of procoagulant activity in human cancer-cells cultured "in vitro" or in cells isolated from human tumor-tissues[J]. Thromb Haemost, 1993, 69 (4): 335- 338
doi: 10.1055/s-0038-1651608
54 HAMADA K , KURATSU J , SAITOH Y et al. Expression of tissue factor correlates with grade of malignancy in human glioma[J]. Cancer, 1996, 77 (9): 1877- 1883
doi: 10.1002/(SICI)1097-0142(19960501)77:9<1877::AID-CNCR18>3.0.CO;2-X
[1] 林翠翠, 陈正云, 王春艳, 席咏梅. 基于脂质组学的子宫内膜异位症生物标志物研究进展[J]. 浙江大学学报（医学版）, 2020, 49(6): 779-784.
[2] 李梦瑶,刘盼,柯越海,张雪. 放射性肺损伤中巨噬细胞作用机制的研究进展[J]. 浙江大学学报（医学版）, 2020, 49(5): 623-628.
[3] 韩雪,蒋国军,石巧娟. 降血糖药对内皮祖细胞作用的研究进展[J]. 浙江大学学报（医学版）, 2020, 49(5): 629-636.
[4] 段润平,许叶圣,郑利斌,姚玉峰. 病毒感染性眼病病原学诊断的研究进展[J]. 浙江大学学报（医学版）, 2020, 49(5): 644-650.
[5] 吴唯,徐键. 正五聚蛋白3在多囊卵巢综合征中的作用研究进展[J]. 浙江大学学报（医学版）, 2020, 49(5): 637-643.
[6] 徐清霖,楼国东,王甜甜,张力三. 发作性睡病的药物治疗进展[J]. 浙江大学学报（医学版）, 2020, 49(4): 419-424.
[7] 蒋沛然,王志萍. 模式生物神经轴突再生的研究进展[J]. 浙江大学学报（医学版）, 2020, 49(4): 500-507.
[8] 陈峻逸,杨翔,方学贤,王福俤,闵军霞. 铁死亡与重大慢性疾病[J]. 浙江大学学报（医学版）, 2020, 49(1): 44-57.
[9] 俞卿, 熊秀芳, 孙毅. 靶向Cullin-RING E3泛素连接酶的抗肿瘤策略及相关药物研发进展[J]. 浙江大学学报（医学版）, 2020, 49(1): 1-19.
[10] 段玲艳,尹香菊,孟红恩,方学贤,闵军霞,王福俤. 铁稳态代谢表观遗传调控机制的研究进展[J]. 浙江大学学报（医学版）, 2020, 49(1): 58-70.
[11] 李艾,张添源,高建青. 间充质干细胞的肿瘤归巢特性及其肿瘤靶向治疗应用研究进展[J]. 浙江大学学报（医学版）, 2020, 49(1): 20-34.
[12] 黄耀凭,杨凤,周天华,谢珊珊. Hippo信号通路及其在消化系统肿瘤中的作用研究进展[J]. 浙江大学学报（医学版）, 2020, 49(1): 35-43.
[13] 钟文,楼燕,邱宸阳,李栋林,张鸿坤. 髂静脉支架植入术后药物治疗策略研究进展[J]. 浙江大学学报（医学版）, 2020, 49(1): 131-136.
[14] 徐亦鸣,应可净. 中性粒细胞胞外诱捕网与肿瘤相关研究进展[J]. 浙江大学学报（医学版）, 2020, 49(1): 107-112.
[15] 刘晓晓,郭莉琼,梁成. 抗N-甲基-D-天冬氨酸受体脑炎患者脑电图特点的研究进展[J]. 浙江大学学报（医学版）, 2020, 49(1): 118-123.