增加肿瘤患者血栓风险的药物概述

摘要/Abstract

摘要： 静脉血栓栓塞（venous thromboembolism, VTE）是肿瘤患者常见的危及生命的并发症,1年生存率约12%,而无肿瘤VTE患者1年生存率36%。肿瘤患者发生血栓有多重因素,由于凝血因子变化使血液处于高凝状态,手术、创伤、中心静脉置管、肿瘤病理类型及分级等都是增加VTE发生的风险因素。此外,细胞毒性化疗药物、激素治疗等也增加血栓栓塞和动脉栓塞的风险,肿瘤化疗患者VTE平均年发生率约11%,有的药物引起VTE发生率可增加至20%。此外,抗血管生成药物,支持治疗等也增加VTE 风险。目前,许多探索肿瘤化疗后引起高凝状态的基础和临床研究正在进行中。本研究对肿瘤化疗等药物增加VTE和动脉血栓的风险相关临床研究进行总结分析,为临床肿瘤药物治疗过程预防血栓风险提供参考。

关键词: 静脉血栓, 肿瘤, 化疗, 血栓形成

Abstract: Venous thromboembolism(VTE) is a frequent and potential life threatening complication associated with tumor malignancies. In patients with cancer, VTE portends a poor prognosis, in fact, only 12% of those who suffer an event will survive beyond one year. There are several different risk factors for the development of VTE in cancer patients that are well-described in the literature. Cancer is often associated with hypercoagulability due to changes in coagulation factors, local venous stasis, surgery, and the presence of a central venous catheter. In addition, chemotherapy drugs may further increase the risk of thromboembolic disease. The annual incidence of VTE in patients receiving chemotherapy is estimated at 11%. This risk can climb to 20% or higher depending on the type of drugs being administered. In addition to chemotherapy, there are many other anti-neoplastic and supportive therapies that are also associated with an increased risk for the development of VTE. At present, several original basic science studies and clinical trials are underway in an effort to enhance our understanding of the mechanisms by which different chemotherapeutic agents can generate a prothrombotic state. The purpose of this article is to review the pertinent literature related to VTE in malignancy, chemotherapy and other cancer-related treatments associated with VTE, and to provide reference for prevention of thrombosis risk in medication therapy of tumors.

Key words: venous thromboembolism, cancer, chemotherapy, thrombosis

中图分类号:

R965

崔向丽, 万子睿, 侯珂露, 杨辉, 于晓佳, 郑芸颖, 刘丽宏*, 杨媛华. 增加肿瘤患者血栓风险的药物概述[J]. 中国药物警戒, 2017, 14(7): 430-434.

CUI Xiang-li, WAN Zi-rui, HOU Ke-lu, YANG Hui, YU Xiao-jia, ZHENG Yun-ying, LIU Li-hong*, YANG Yuan-hua. Overview of Dugs Increasing the Risk of VTE or Thrombosis in Patients with Cancer[J]. Chinese Journal of Pharmacovigilance, 2017, 14(7): 430-434.

参考文献

[1] Shinagare A B, Guo M, Hatabu H, et al. Incidence of pulmonary embolism in oncologic outpatients at a tertiary cancer center[J]. Cancer, 2011,117(16):3860-3866.
[2] Blom J W, Vanderschoot J P, Oostindi r M J, et al Incidence of venous thrombosis in a large cohort of 66329.cancer patients: results of a record linkage study[J]. J Thromb Haemost,2006, 4(3):529-535.
[3] Oppelt P, Betbadal A, Nayak L. Approach to chemotherapy-associated thrombosis[J]. Vasc Med, 2015, 20(2):153-161.
[4] Zangari M, Fink L, Zhan F, et al . Low venous thromboembolic risk with bortezomib in multiple myeloma and potential protective effect with thalidomide/lenalidomide-based therapy: review of data from phase 3 trials and studies of novel combination regimens[J]. Clin Lymphoma Myeloma Leuk, 2011, 11(2):228-236.
[5] Moore R A, Adel N, Riedel E, et al. High incidence of thromboembolic events in patients treated with cisplatin-based chemoth-erapy: a large retrospective analysis[J]. J Clin Oncol, 2011, 29(25):3466-3473.
[6] 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.
[7] Petrelli F, Cabiddu M, Borgonovo K, et al . Risk of venous and arterial thromboembolic events associated with anti-EGFR agents: a meta-analysis of randomized clinical trials[J]. Ann Oncol,2012; 23(7):1672-1676.
[8] Ferroni P, Guadagni F, Laudisi A, et al. Estimated glomerular filtration rate is an easy predictor of venous thromboembolism in cancer patients undergoing platinum-based chemotherapy[J]. Oncologist, 2014, 19(5):562-567.
[9] 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.
[10] Priest J R, Ramsay N K, Steinherz P G, et al. A syndrome of thrombosis and hemorrhage complicating L-asparaginase therapy for childhood acute lymphoblastic leukemia[J]. J Pediatr,1982,100(6):984-989.
[11] Truelove E, Fielding A K, Hunt B J. The coagulopathy and thrombotic risk associated with Lasparaginase treatment in adults with acute lymphoblastic leukaemia[J]. Leukemia, 2013, 27(3):553-559.
[12] Qureshi A, Mitchell C, Richards S, et al. Asparaginase-related venous thrombosis in UKALL 2003- re-exposure to asparaginase is feasible and safe[J]. Br J Haematol, 2010,149(3):410-413.
[13] Hsieh P C, MacGillivray C, Gannon J, et al. Local controlled intramyocardial delivery of platelet-derived growth factor improves postinfarction ventricular function without pulmonary toxicity[J]. Circulation, 2006, 114(7):637-644.
[14] Bearman S. The syndrome of hepatic veno-occlusive disease after marrow transplantation[J]. Blood 1995, 85(11):3005-3020.
[15] McDonald G, Hinds M, Fisher L, et al. Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients[J]. Ann Intern Med, 1993, 118(4):255-267.
[16] Alahmari A K, Almalki Z S, Alahmari A K, et al. Thromboembolic Events Associated with Bevacizumab plus Chemotherapy for Patients with Colorectal Cancer: A Meta-Analysis of Randomized Controlled Trials[J]. Am Health Drug Benefits.2016,9 (4):221-232.
[17] Petrelli F, Cabiddu M, Borgonovo K, et al. Risk of venous and arterial thromboembolic events associated with anti-EGFR agents: a meta-analysis of randomized clinical trials[J]. Ann Oncol, 2012, 23(7):1672-1679.
[18] Miroddi M, Sterrantino C, Simmonds M, et al. Systematic review and meta-analysis of the risk of severe and life-threatening throm-boembolism in cancer patients receiving anti-EGFR monoclonal antibodies (cetuximab or panitumumab)[J]. Int J Cancer, 2016, 139(10):2370-2380.
[19] Cuzick J, Forbes J, Edwards R, et al. First results from the International Breast Cancer Intervention Study (IBIS-I): a randomised prevention trial[J]. Lancet, 2002, 360(9336):817-824.
[20] Onitilo AA, Doi S A, Engel J M, et al. Clustering of venous thrombosis events at the start of tamoxifen therapy in breast cancer: a population-based experience[J]. Thromb Res, 2012, 130(1):27-31.
[21] Molina MAB, Lozano M, Cano A, et al. Progestin-only contraception and venous thromboembolism[J]. Thrombosis Research, 2012, 129(5) :e257-e262.
[22] Olié V, Canonico M, Scarabin P Y. Risk of venous thrombosis with oral versus transdermal estrogen therapy among postmeenop-ausal women[J]. Curr Opin Hematol, 2010, 17(5): 457-463.
[23] Bundred N J. The effects of aromatase inhibitors on lipids and thrombosis[J].British Journal of Cancer, 2005, 93(Suppl 1), S23- S27.
[24] Coombes R C, Hall E, Gibson L J, et al. A randomized trial of exemestane after two to three years of tamoxifen therapy in postme-nopausal women with primary breast cancer[J]. N Engl J Med, 2004, 350(1):1081 - 1092.
[25] 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.
[26] Steurer M, Sudmeier I, Stauder R, et al. Thromboembolic events in patients with myelodysplastic syndrome receiving thalidomide in combination with darbepoietin alpha[J]. Br J Haematol, 2003, 121(1):101-103.
[27] Wun T, Law L, Harvey D, et al. Increased incidence of symptomatic venous thrombosis in patients with cervical carcinoma treated with concurrent chemotherapy, radiation, and erythropoietin[J].Cancer, 2003, 98(7):1514-1520.
[28] Bennett C L, Silver S M, Djulbegovic B, et al. Venous Thromboembolism and Mortality Associated With Recombinant Erythro-poietin and Darbepoetin Administration for the Treatment of Cancer-Associated Anemia[J]. JAMA, 2008, 299(8): 914-924.
[29] Stasko J, Drouet L, Soria C,et al.Erythropoietin and granulocyte colony-stimulating factor increase plasminogen activator inhibitor-1 release in HUVEC culture[J]. Thromb Res, 2002, 105(2):161-164.
[30] 沙建慧, 黄兰玲, 夏文春. 地塞米松对小鼠血栓形成的影响[J]. 吉林大学学报医学版, 2002, 28(2): 216-218.
[31] Johannesdottir S A, Horváth-Puhó E, Dekkers O M,et al. Use of glucocorticoids and risk of venous thromboembolism[J]. Thorax, 2013, 69(8):379.