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摘要: 多发性骨髓瘤(MM)为浆细胞异常增生的恶性肿瘤，是发生静脉血栓栓塞症(VTE)的高风险血液系统肿瘤之一。凝血纤溶系统紊乱、炎症因子分泌增多、血小板过度激活、内皮细胞损伤等多种机制参与MM高凝状态的形成。免疫调节药物的应用进一步增加了MM患者VTE的发生率。国际骨髓瘤工作组(IMWG)提出的血栓风险分层因预测能力低、预防效果欠佳而备受争议。本文结合国内外相关研究对MM合并VTE的发生机制及预防进展做一综述。Abstract: Multiple myeloma(MM) is a malignant tumor with abnormal proliferation of plasma cells, which is one of the hematologic malignancies with high risk of venous thromboembolism(VTE). The disorder of coagulation and fibrinolysis system, increased secretion of inflammatory factors, platelet hyperactivation, injury of endothelial cells and other mechanisms are involved in the formation of MM hypercoagulant state. The use of immunomodulatory drugs further increased the incidence of VTE in MM patients. The recommendations proposed by the International Myeloma Working Group(IMWG) remain controversial due to its poor predictive ability and prevention effect. In this article, the pathogenesis and prevention of MM with VTE are reviewed based on recent research progress in China and abroad.
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Key words:
- multiple myeloma /
- venous thromboembolism /
- thromboprophylaxis
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危险因素 分值 患者相关因素 高龄(年龄>75岁) 1 肥胖(BMI>25 kg/m2) 1 VTE病史 1 合并症(肝肾损害、慢性阻塞性肺疾病、糖尿病、慢性炎症性肠病等) 1 中心静脉置管 1 手术或制动 1 疾病相关因素 骨髓瘤诊断 1 高粘滞血症 1 治疗相关因素 免疫调节药物 1 大剂量地塞米松(>480 mg/周期) 1 多柔比星 1 多药联合化疗 1 促红素的使用 1 总分≤1：低风险；总分≥2：高风险。 
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表 2 MM患者SAVED评分[27]
首字母缩写/英文 危险因素 分值 S/Surgery 近90天手术史 +2 A/Asian race 亚洲种族 -3 V/VTE history 既往VTE史 +3 E/Eighty 年龄≥80岁 +1 D/Dexamethasone 地塞米松 大剂量(>160 mg/周期) +2 标准剂量(120~160 mg/周期) +1 总分≤1：低风险；总分≥2：高风险。
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表 3 MM患者IMPEDE VTE评分[26]
首字母缩写/英文 危险因素 分值 I/Immunomodulatory drug 免疫调节药物 +4 M/Body mass index BMI≥25 kg/m2 +1 P/Pelvic，hip or femur fracture 骨盆、髋部或股骨骨折 +4 E/Erythropoiesis-stimulating agent 促红细胞生成药物 +1 D/Doxorubicin 多柔比星 +3 Dexamethasone 地塞米松 大剂量(>160 mg/月) +4 标准剂量(≤160 mg/月) +2 E/Ethnicity/race 亚洲种族 -3 V/History of venous thromboembolism 既往VTE病史 +5 T/Tunneled line/central venous catheter 中心静脉置管 +2 E/Existing thromboprophylaxis 血栓预防治疗 治疗性低分子肝素或华法林 -4 预防性低分子肝素或阿司匹林 -3 总分≤3：低风险；总分4~7：中风险；总分≥8：高风险。
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[1] Kekre N, Connors JM. Venous thromboembolism incidence in hematologic malignancies[J]. Blood Rev, 2019, 33: 24-32. doi: 10.1016/j.blre.2018.06.002
[2] Fotiou D, Sergentanis TN, Papageorgiou L, et al. Longer procoagulant phospholipid-dependent clotting time, lower endogenous thrombin potential and higher tissue factor pathway inhibitor concentrations are associated with increased VTE occurrence in patients with newly diagnosed multiple myeloma: results of the prospective ROADMAP-MM-CAT study[J]. Blood Cancer J, 2018, 8(11): 102. doi: 10.1038/s41408-018-0135-y
[3] Chakraborty R, Bin Riaz I, Malik SU, et al. Venous thromboembolism risk with contemporary lenalidomide-based regimens despite thromboprophylaxis in multiple myeloma: A systematic review and meta-analysis[J]. Cancer, 2020, 126(8): 1640-1650. doi: 10.1002/cncr.32682
[4] Sanfilippo KM. Assessing the risk of venous thromboembolism in multiple myeloma[J]. Thromb Res, 2020, 191 Suppl 1: S74-S78.
[5] Baker HA, Brown AR, Mahnken JD, et al. Application of risk factors for venous thromboembolism in patients with multiple myeloma starting chemotherapy, a real-world evaluation[J]. Cancer Med, 2019, 8(1): 455-462. doi: 10.1002/cam4.1927
[6] Bradbury CA, Craig Z, Cook G, et al. Thrombosis in patients with myeloma treated in the Myeloma Ⅸ and Myeloma Ⅺ phase 3 randomized controlled trials[J]. Blood, 2020, 136(9): 1091-1104. doi: 10.1182/blood.2020005125
[7] Auwerda JJ, 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
[8] Yaǧci M, Sucak G, Haznedar R. Fibrinolytic activity in multiple myeloma[J]. Am J Hematol, 2003, 74(4): 231-237. doi: 10.1002/ajh.10433
[9] Uaprasert N, Voorhees PM, Mackman N, et al. Venous thromboembolism in multiple myeloma: current perspectives in pathogenesis[J]. Eur J Cancer, 2010, 46(10): 1790-1799. doi: 10.1016/j.ejca.2010.03.007
[10] Auwerda JJ, Sonneveld P, de Maat MP, et al. Prothrombotic coagulation abnormalities in patients with newly diagnosed multiple myeloma[J]. Haematologica, 2007, 92(2): 279-280. doi: 10.3324/haematol.10454
[11] Sokol J, Hrncar M, Nehaj F, et al. Plasma Levels of Vascular Endothelial Growth Factor and Selected Hemostatic Parameters in Association With Treatment Response in Multiple Myeloma[J]. Clin Appl Thromb Hemost, 2019, 25: 1-6.
[12] O'Sullivan LR, Meade-Murphy G, Gilligan OM, et al. Platelet hyperactivation in multiple myeloma is also evident in patients with premalignant monoclonal gammopathy of undetermined significance[J]. Br J Haematol, 2021, 192(2): 322-332. doi: 10.1111/bjh.16774
[13] Elice F, Fink L, Tricot G, et al. Acquired resistance to activated protein C(aAPCR)in multiple myeloma is a transitory abnormality associated with an increased risk of venous thromboembolism[J]. Br J Haematol, 2006, 134(4): 399-405. doi: 10.1111/j.1365-2141.2006.06208.x
[14] Crowley MP, Kevane B, O'Shea SI, et al. Plasma Thrombin Generation and Sensitivity to Activated Protein C Among Patients With Myeloma and Monoclonal Gammopathy of Undetermined Significance[J]. Clin Appl Thromb Hemost, 2016, 22(6): 554-562. doi: 10.1177/1076029615625825
[15] 赵永峰, 任宏波. 免疫调剂药物治疗多发性骨髓瘤发生深静脉血栓风险的系统评价和Meta分析[J]. 临床血液学杂志, 2019, 32(7): 527-531. doi: 10.13201/j.issn.1004-2806.2019.07.009
[16] 韩虹晓, 李剑. 多发性骨髓瘤与静脉血栓形成[J]. 临床血液学杂志, 2020, 33(7): 456-459. https://www.cnki.com.cn/Article/CJFDTOTAL-LCXZ202007004.htm
[17] Li W, Garcia D, Cornell RF, et al. Cardiovascular and Thrombotic Complications of Novel Multiple Myeloma Therapies: A Review[J]. JAMA Oncol, 2017, 3(7): 980-988. doi: 10.1001/jamaoncol.2016.3350
[18] Fotiou D, Gavriatopoulou M, Terpos E. Multiple Myeloma and Thrombosis: Prophylaxis and Risk Prediction Tools[J]. Cancers, 2020, 12(1): 191. doi: 10.3390/cancers12010191
[19] Bagratuni T, Kastritis E, Politou M, et al. Clinical and genetic factors associated with venous thromboembolism in myeloma patients treated with lenalidomide-based regimens[J]. Am J Hematol, 2013, 88(9): 765-770. doi: 10.1002/ajh.23504
[20] Anaissie EJ, Coleman EA, Goodwin JA, et al. Prophylactic recombinant erythropoietin therapy and thalidomide are predictors of venous thromboembolism in patients with multiple myeloma: limited effectiveness of thromboprophylaxis[J]. Cancer, 2012, 118(2): 549-557. doi: 10.1002/cncr.26302
[21] Chalayer E, Chapelle C, Leleu X, et al. Usual risk factors do not predict venous thromboembolism in newly diagnosed myeloma treated with immunomodulatory drugs[J]. Am J Hematol, 2016, 91(10): E455-E456. doi: 10.1002/ajh.24454
[22] Palumbo A, Rajkumar SV, San Miguel JF, et al. International Myeloma Working Group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation[J]. J Clin Oncol, 2014, 32(6): 587-600. doi: 10.1200/JCO.2013.48.7934
[23] Streiff MB, Holmstrom B, Angelini D, et al. NCCN Guidelines Insights: Cancer-Associated Venous Thromboembolic Disease, Version 2.2018[J]. J Natl Compr Canc Netw, 2018, 16(11): 1289-1303. doi: 10.6004/jnccn.2018.0084
[24] Calafiore V, Giamporcaro S, Conticello C, et al. A Real-Life Survey of Venous Thromboembolic Events Occurring in Myeloma Patients Treated in Third Line with Second-Generation Novel Agents[J]. J Clin Med, 2020, 9(9): 2876. doi: 10.3390/jcm9092876
[25] 唐晓霞, 周泽平, 毕慧, 等. 多发性骨髓瘤病人血栓预防情况的调查分析[J]. 安徽医药, 2019, 23(2): 395-398. doi: 10.3969/j.issn.1009-6469.2019.02.051
[26] Sanfilippo KM, Luo S, Wang TF, et al. Predicting venous thromboembolism in multiple myeloma: development and validation of the IMPEDE VTE score[J]. Am J Hematol, 2019, 94(11): 1176-1184. doi: 10.1002/ajh.25603
[27] Li A, Wu Q, Luo S, et al. Derivation and Validation of a Risk Assessment Model for Immunomodulatory Drug-Associated Thrombosis Among Patients With Multiple Myeloma[J]. J Natl Compr Canc Netw, 2019, 17(7): 840-847. doi: 10.6004/jnccn.2018.7273
[28] Chalayer E, Teste A, Guyotat D, et al. Predicting the risk of venous thromboembolism in newly diagnosed myeloma with immunomodulatory drugs: External validation of the IMPEDE VTE score[J]. Am J Hematol, 2020, 95(1): E18-E20. doi: 10.1002/ajh.25659
[29] Fotiou D, Gavriatopoulou M, Ntanasis-Stathopoulos I, et al. Updates on thrombotic events associated with multiple myeloma[J]. Expert Rev Hematol, 2019, 12(5): 355-365. doi: 10.1080/17474086.2019.1604214
[30] Syrigos K, Grapsa D, Sangare R, et al. Prospective Assessment of Clinical Risk Factors and Biomarkers of Hypercoagulability for the Identification of Patients with Lung Adenocarcinoma at Risk for Cancer-Associated Thrombosis: The Observational ROADMAP-CAT Study[J]. Oncologist, 2018, 23(11): 1372-1381. doi: 10.1634/theoncologist.2017-0530
[31] Palumbo A, Cavo M, Bringhen S, et al. Aspirin, warfarin, or enoxaparin thromboprophylaxis in patients with multiple myeloma treated with thalidomide: a phase Ⅲ, open-label, randomized trial[J]. J Clin Oncol, 2011, 29(8): 986-993. doi: 10.1200/JCO.2010.31.6844
[32] Zoppellaro G, Veronese N, Granziera S, et al. Primary thromboembolic prevention in multiple myeloma patients: An exploratory meta-analysis on aspirin use[J]. Semin Hematol, 2018, 55(4): 182-184. doi: 10.1053/j.seminhematol.2017.08.002
[33] Takaishi K, Tsukamoto S, Ohwada C, et al. Low incidence of thromboembolism in multiple myeloma patients receiving immunomodulatory drugs; a retrospective single-institution analysis[J]. J Thromb Thrombolysis, 2019, 48(1): 141-148. doi: 10.1007/s11239-019-01809-w
[34] Cornell RF, Goldhaber SZ, Engelhardt BG, et al. Primary prevention of venous thromboembolism with apixaban for multiple myeloma patients receiving immunomodulatory agents[J]. Br J Haematol, 2020, 190(4): 555-561. doi: 10.1111/bjh.16653
[35] Wang TF, Delluc A. Thromboprophylaxis in patients with multiple myeloma[J]. Br J Haematol, 2020, 190(4): 493-494. doi: 10.1111/bjh.16731
[36] Storrar NPF, Mathur A, Johnson PRE, et al. Safety and efficacy of apixaban for routine thromboprophylaxis in myeloma patients treated with thalidomide-and lenalidomide-containing regimens[J]. Br J Haematol, 2019, 185(1): 142-144. doi: 10.1111/bjh.15392
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| 引用本文: |
赵冰妮, 杨林花. 多发性骨髓瘤合并静脉血栓栓塞症的研究进展[J]. 临床血液学杂志, 2022, 35(5): 383-387. doi: 10.13201/j.issn.1004-2806.2022.05.017
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| Citation: |
ZHAO Bingni, YANG Linhua. Research progress on multiple myeloma complicated with venous thromboembolism[J]. J Clin Hematol, 2022, 35(5): 383-387. doi: 10.13201/j.issn.1004-2806.2022.05.017
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