肿瘤合并肝损伤患者血小板减少症管理中国专家共识(2022版)

中国抗癌协会肿瘤支持治疗专业委员会

doi:10.3969/j.issn.1001-5256.2023.06.005

肿瘤合并肝损伤患者血小板减少症管理中国专家共识(2022版)

DOI: 10.3969/j.issn.1001-5256.2023.06.005

中国抗癌协会肿瘤支持治疗专业委员会

利益冲突声明：所有作者声明无利益冲突。

通信作者: 袁响林，yuanxianglin@hust.edu.cn
本文首次发表于[肿瘤防治研究，2023，50(3)：211-223]

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出版历程
- 收稿日期: 2023-04-14
- 录用日期: 2023-05-20
- 出版日期: 2023-06-20

Chinese expert consensus on management of thrombocytopenia in cancer patients with liver injury (2022 edition)

Committee of Neoplastic Supportive-care (CONS), China Anti-Cancer Association

摘要

摘要: 血小板减少症和肝损伤是肿瘤患者常见且严重的临床问题。肿瘤合并肝损伤患者血小板减少症(TCLI)的病因更加复杂，但常见于肝损伤和肿瘤治疗。肿瘤治疗所致血小板减少症的管理已逐渐形成规范，肝损伤相关血小板减少症随着相关药物的获批上市，管理日益明晰。但肿瘤合并肝损伤患者血小板减少症的管理仍是空白，血小板减少症和肝损伤的叠加进一步增加了肿瘤治疗的难度。为此，中国抗癌协会肿瘤支持治疗专业委员会组织专家对文献进行分析和讨论，形成肿瘤合并肝损伤患者血小板减少症管理中国专家共识(2022版)，以指导临床实践。
- 肿瘤 /
- 肝病 /
- 肝损伤 /
- 血小板减少症 /
- 专家共识
Abstract: Thrombocytopenia and liver injury are common and serious clinical problems in cancer patients. The etiology of thrombocytopenia in cancer patients with liver injury (TCLI) is complicated, which is common in liver injury and tumor treatment. The management of cancer therapy-induced thrombocytopenia has gradually become standardized, and the management of liver injury-associated thrombocytopenia is becoming clear with the approval and marketing of relevant drugs. However, the management of TCLI is still blank, and the superposition of thrombocytopenia and liver injury further increases the difficulty of cancer treatment. Therefore, the Committee of Neoplastic Supportive-care, China Anti-Cancer Association organizes experts to analyze and discuss relevant literatures to form a Chinese expert consensus on the management of thrombocytopenia in cancer patients with liver injury (2022 Edition) to guide clinical practice.
- Cancer /
- Liver Disease /
- Liver Injury /
- Thrombocytopenia /
- Expert Consensus

HTML全文

图 1 肿瘤合并原发肝病相关血小板减少症管理流程

Figure 1. Management of thrombocytopenia in cancer patients with primary liver disease

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图 2 MDT执行流程

Figure 2. MDT execution process

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表 1 循证医学证据等级及定义

Table 1. Levels of evidence-based medical proof and definitions

证据等级	定义
Ⅰ级(高质量)	进一步研究几乎不可能改变对临床疗效评估结果的可信度，为高级别证据
Ⅱ级(中等质量)	进一步研究可能改变对疗效评估结果的可信度有重要影响，为中级别证据
Ⅲ级(低质量)	进一步研究很有可能改变对疗效评估结果的可信度有重要影响，且极有可能改变评估结果，为低级别证据
Ⅳ级(极低质量)	任何疗效评估结果都不确定，为极低级别证据

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表 2 推荐级别及定义

Table 2. Recommendation grades and definitions

推荐级别	定义
推荐	基于可获得证据，非常确定获益大于风险和负担，则作出推荐
弱推荐	基于可获得证据，认为获益、风险和负担相当平衡，或获益、风险的程度存在明显不确定性，则作出弱推荐

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表 3 血小板减少症鉴别诊断

Table 3. Differential diagnosis of thrombocytopenia

疾病		检查项目
感染	严重感染	血常规：C反应蛋白；降钙素原
	病毒感染	EB病毒、巨细胞病毒、HIV
血液系统疾病	溶血性贫血；阵发性睡眠血红蛋白尿再生障碍性贫血、肿瘤骨髓转移免疫性血小板减少症	乳酸脱氢酶骨髓涂片、骨髓活检血小板糖蛋白特异性自身抗体
自身免疫性疾病	系统性红斑狼疮、干燥综合征、类风湿关节炎等	抗核抗体、类风湿因子
血栓性疾病	弥漫性血管内凝血	凝血酶原时间、部分活化凝血酶原时间、凝血酶时间、纤维蛋白原、D二聚体、纤维蛋白降解产物
肾功能损伤	肾功能损害相关的血小板减少	肌酐
营养不良	营养不良相关血小板减少	维生素B₁₂、叶酸
抗肿瘤治疗和/或其他药物治疗相关血小板减少症	化疗(如铂类、吉西他滨、卡培他滨、替莫唑胺等)、放疗、免疫检查点抑制剂、靶向治疗(如仑伐替尼、伊马替尼、泽布替尼、尼拉帕利等)、抗体偶联药物(如ADC-恩美曲妥珠单抗等)、抗生素、肝素等	血常规，血小板减少发生前有确切的应用某种引起血小板减少症的药物，且停药后血小板计数恢复正常

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表 4 中国获批上市TPO受体激动剂

Table 4. TPO-RAs approved for marketing in China

项目	罗普司亭	艾曲泊帕	阿伐曲泊帕	海曲泊帕
TPO受体结合形式	胞外	跨膜	跨膜	跨膜
给药途径	皮下注射	口服	口服	口服
饮食影响	无	是	无	是
与阳离子相互作用	无	++	无	++
东亚人群需减少剂量	否	是	否	是
肝功能不全者需减少剂量	否	是	否	是
需增加肝功能检查	否	+	否	?
可否用于肾衰竭	是	可能可以	可能可以	无数据
可否孕期使用	否	否	否	否
国内获批适应证	ITP	ITP	肝病相关血小板减少症	ITP、SAA

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表 5 临床常见引起肝损伤的抗肿瘤药物

Table 5. Common anti-cancer drugs causing liver injury in clinical practice

肿瘤药物分类	典型药物
铂类药物	奥沙利铂、卡铂等
抗代谢药物	甲氨蝶呤、阿糖胞苷、吉西他滨等
烷化剂类药物	环磷酰胺、异环磷酰胺、白消安等
分子靶向类药物	伊马替尼、达沙替尼、拉帕替尼、厄洛替尼、仑伐替尼、索拉非尼、贝伐珠单抗、吉妥珠单抗、曲妥珠单抗等
免疫检查点抑制剂	纳武单抗、帕博利珠单抗、伊匹单抗等
其他	伊立替康、ADCs等

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参考文献(87)

[1]	People's Liberation Army Professional Committee of Critical Care Medicine, CMA Chinese Society of Laboratory Medicine. Expert consensus on the diagnosis and treatment of thrombocytopenia in adult critical care patients in China[J]. Med J Chin PLA, 2020, 45(5): 457-474. DOI: 10.11855/j.issn.0577-7402.2020.05.01. 全军重症医学专业委员会, 中华医学会检验医学分会. 中国成人重症患者血小板减少诊疗专家共识[J]. 解放军医学杂志, 2020, 45(5): 457-474. DOI: 10.11855/j.issn.0577-7402.2020.05.01.
[2]	GUYATT GH, OXMAN AD, VIST GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations[J]. BMJ, 2008, 336(7650): 924-926. DOI: 10.1136/bmj.39489.470347.AD.
[3]	XIAO J, WANG F, WONG NK, et al. Global liver disease burdens and research trends: Analysis from a Chinese perspective[J]. J Hepatol, 2019, 71(1): 212-221. DOI: 10.1016/j.jhep.2019.03.004.
[4]	GANGIREDDY VG, KANNEGANTI PC, SRIDHAR S, et al. Management of thrombocytopenia in advanced liver disease[J]. Can J Gastroenterol Hepatol, 2014, 28(10): 558-564. DOI: 10.1155/2014/532191.
[5]	MAAN R, de KNEGT RJ, VELDT BJ. Management of thrombocytopenia in chronic liver disease: focus on pharmacotherapeutic strategies[J]. Drugs, 2015, 75(17): 1981-1992. DOI: 10.1007/s40265-015-0480-0.
[6]	YOSHIDA M, TATEISHI R, HIROI S, et al. Changes in platelet counts and thrombocytopenia risk in patients with chronic liver disease with different etiologies using real-world Japanese data[J]. Adv Ther, 2022, 39(2): 992-1003. DOI: 10.1007/s12325-021-02008-x.
[7]	HUANG CE, CHANG JJ, WU YY, et al. Different impacts of common risk factors associated with thrombocytopenia in patients with hepatitis B virus and hepatitis C virus infection[J]. Biomed J, 2022, 45(5): 788-797. DOI: 10.1016/j.bj.2021.09.001.
[8]	SCHARF RE. Thrombocytopenia and hemostatic changes in acute and chronic liver disease: Pathophysiology, clinical and laboratory features, and management[J]. J Clin Med, 2021, 10(7): 1530. DOI: 10.3390/jcm10071530.
[9]	GALLO P, TERRACCIANI F, DI PASQUALE G, et al. Thrombocytopenia in chronic liver disease: Physiopathology and new therapeutic strategies before invasive procedures[J]. World J Gastroenterol, 2022, 28(30): 4061-4074. DOI: 10.3748/wjg.v28.i30.4061.
[10]	LI SS, LIU Q, HUANG LW. Causes of thrombocytopenia in chronic liver disease[J/CD]. Chin J Liver Dis (Electronic Version), 2021, 13(2): 24-28. DOI: 10.3969/j.issn.1674-7380.2021.02.005. 李尚书, 刘群, 黄丽雯. 慢性肝病血小板减少的原因[J/CD]. 中国肝脏病杂志(电子版), 2021, 13(2): 24-28. DOI: 10.3969/j.issn.1674-7380.2021.02.005.
[11]	PRADELLA P, BONETTO S, TURCHETTO S, et al. Platelet production and destruction in liver cirrhosis[J]. J Hepatol, 2011, 54(5): 894-900. DOI: 10.1016/j.jhep.2010.08.018.
[12]	KAJIHARA M, KATO S, OKAZAKI Y, et al. A role of autoantibody-mediated platelet destruction in thrombocytopenia in patients with cirrhosis[J]. Hepatology, 2003, 37(6): 1267-1276. DOI: 10.1053/jhep.2003.50209.
[13]	UEMURA M, FUJIMURA Y, MATSUMOTO M, et al. Comprehensive analysis of ADAMTS13 in patients with liver cirrhosis[J]. Thromb Haemost, 2008, 99(6): 1019-1029. DOI: 10.1160/TH08-01-0006.
[14]	SHAHIDI M. Thrombosis and von willebrand factor[J]. Adv Exp Med Biol, 2017, 906: 285-306. DOI: 10.1007/5584_2016_122.
[15]	BROWN RS Jr. Current management of thrombocytopenia in chronic liver disease[J]. Gastroenterol Hepatol (N Y), 2019, 15(3): 155-157.
[16]	Chinese Society of Infectious Diseases, Chinese Medical Association, Expert Committee for Prevention and Management of Liver Inflammation. Consensus statement by the expert committee for prevention and management of liver inflammation in China[J]. Chin J Clin Infect Dis, 2014, 7(1): 4-12. DOI: 10.3760/cma.j.issn.1674-2397.2014.01.002. 中华医学会感染病学分会, 肝脏炎症及其防治专家共识专家委员会. 肝脏炎症及其防治专家共识[J]. 中华临床感染病杂志, 2014, 7(1): 4-12. DOI: 10.3760/cma.j.issn.1674-2397.2014.01.002.
[17]	Chinese Society of Hepatology, Chinese Medical Association. Guidelines on the diagnosis and management of autoimmune hepatitis (2021)[J]. J Clin Hepatol, 2022, 38(1): 42-49. DOI: 10.3760/cma.j.cn112138-20211112-00796 中华医学会肝病学分会. 自身免疫性肝炎诊断和治疗指南(2021)[J]. 临床肝胆病杂志, 2022, 38(1): 42-49. DOI: 10.3760/cma.j.cn112138-20211112-00796
[18]	Chinese Society of Infectious Diseases, Chinese Medical Association, Chinese Society of Hepatology, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B (version 2019)[J]. J Clin Hepatol, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007. 中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎防治指南(2019年版)[J]. 临床肝胆病杂志, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007.
[19]	Chinese Society of Hepatology, Chinese Medical Association, Chinese Society of Infectious Diseases, Chinese Medical Association. Guidelines for the prevention and treatment of hepatitis C(2019 version)[J]. J Clin Hepatol, 2019, 35(12): 2670-2686. DOI: 10.3969/j.issn.1001-5256.2019.12.008. 中华医学会肝病学分会, 中华医学会感染病学分会. 丙型肝炎防治指南(2019年版)[J]. 临床肝胆病杂志, 2019, 35(12): 2670-2686. DOI: 10.3969/j.issn.1001-5256.2019.12.008.
[20]	National Workshop on Fatty Liver and Alcoholic Liver Disease, Chinese Society of Hepatology, Chinese Medical Association, Fatty Liver Expert Committee, Chinese Medical Doctor Association. Guidelines of prevention and treatment for nonalcoholic fatty liver disease: A 2018 update[J]. J Clin Hepatol, 2018, 34(5): 947-957. DOI: 10.3969/j.issn.1001-5256.2018.05.007. 中华医学会肝病学分会脂肪肝和酒精性肝病学组, 中国医师协会脂肪性肝病专家委员会. 非酒精性脂肪性肝病防治指南(2018年更新版)[J]. 临床肝胆病杂志, 2018, 34(5): 947-957. DOI: 10.3969/j.issn.1001-5256.2018.05.007.
[21]	Fatty Liver Expert Committee, Chinese Medical Doctor Association, National Workshop on Fatty Liver and Alcoholic Liver Disease, Chinese Society of Hepatology, Chinese Medical Association. Guidelines of prevention and treatment for alcoholic liver disease: a 2018 update[J]. J Clin Hepatol, 2018, 34(5): 939-946. DOI: 10.3969/j.issn.1001-5256.2018.05.006. 中国医师协会脂肪性肝病专家委员会, 中华医学会肝病学分会脂肪肝和酒精性肝病学组. 酒精性肝病防治指南(2018年更新版)[J]. 临床肝胆病杂志, 2018, 34(5): 939-946. DOI: 10.3969/j.issn.1001-5256.2018.05.006.
[22]	AL-SAMKARI H, SOFF GA. Clinical challenges and promising therapies for chemotherapy-induced thrombocytopenia[J]. Expert Rev Hematol, 2021, 14(5): 437-448. DOI: 10.1080/17474086.2021.1924053.
[23]	SUN YH, LI L, HOU M, et al. Study on the Specific autoantibody in Nonimmune Thrombocytopenia in Malignant Tumor[J]. Cancer Res Clin, 2005, 17(3): 167-169. DOI: 10.3760/cma.j.issn.1006-9801.2005.03.009. 孙亚红, 黎莉, 侯明, 等. 恶性肿瘤非免疫性血小板减少患者血小板特异性抗体的研究[J]. 肿瘤研究与临床, 2005, 17(3): 167-169. DOI: 10.3760/cma.j.issn.1006-9801.2005.03.009.
[24]	WANG HP. Adverse reactions associated with immune checkpoint inhibitor in treatment of liver cancer and related treatment measures[J]. J Clin Hepatol, 2022, 38(5): 985-991. DOI: 10.3969/j.issn.1001-5256.2022.05.003. 王汉萍. 肝癌免疫检查点抑制剂治疗相关不良反应及处理[J]. 临床肝胆病杂志, 2022, 38(5): 985-991. DOI: 10.3969/j.issn.1001-5256.2022.05.003.
[25]	Thrombosis and Hemostasis Group of CMA Chinese Society of Hematology. Chinese guidelines on the diagnosis and treatment of adult primary immune thrombocytopenia(version 2020)[J]. Chin J Hematol, 2020, 41(8): 617-623. DOI: 10.3760/cma.j.issn.0253-2727.2020.08.001. 中华医学会血液学分会血栓与止血学组. 成人原发免疫性血小板减少症诊断与治疗中国指南(2020年版)[J]. 中华血液学杂志, 2020, 41(8): 617-623. DOI: 10.3760/cma.j.issn.0253-2727.2020.08.001.
[26]	Tumor Support and Rehabilitation Therapy Group of CMA Chinese Society of Oncology. Consensus on clinical management of cancer therapy-related thrombocytopenia[J]. Tumor, 2021, 41(12): 812-827. DOI: 10.3781/j.issn.1000-7431.2021.2111-0882. 中华医学会肿瘤学分会肿瘤支持康复治疗学组. 肿瘤治疗相关血小板减少症的临床管理专家共识[J]. 肿瘤, 2021, 41(12): 812-827. DOI: 10.3781/j.issn.1000-7431.2021.2111-0882.
[27]	National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0[M]. Rockville: HHS U S A Department of Health and Human Services, 2017.
[28]	LI Q, CHEN L, YU XH. Differentiation of bone marrow cell morphology of thrombocytopenia in chronic liver disease and primary immune thrombocytopenia[J]. China J Prac Med, 2022, 49(8): 10-12. DOI: 10.3760/cma.j.cn115689-20220122-00349. 李清, 陈雷, 余晓红. 慢性肝病血小板减少症与原发免疫性血小板减少症的骨髓细胞形态的鉴别[J]. 中国实用医刊, 2022, 49(8): 10-12. DOI: 10.3760/cma.j.cn115689-20220122-00349.
[29]	Guidelines Working Committee of Chinese Society of Clinical Oncology. Chinese Society of Clinical Oncology (CSCO) Guidelines for the diagnosis and treatment of cancer therapy-induced thrombocytopenia[M]. Beijing: People's Medical Publishing House, 2022. 中国临床肿瘤学会指南工作委员会. 中国临床肿瘤学会(CSCO) 肿瘤治疗所致血小板减少症诊疗指南2022[M]. 北京: 人民卫生出版社, 2022.
[30]	TRIPODI A, PRIMIGNANI M, CHANTARANGKUL V, et al. Thrombin generation in patients with cirrhosis: the role of platelets[J]. Hepatology, 2006, 44(2): 440-445. DOI: 10.1002/hep.21266.
[31]	TRIPODI A, PRIMIGNANI M, CHANTARANGKUL V, et al. Global hemostasis tests in patients with cirrhosis before and after prophylactic platelet transfusion[J]. Liver Int, 2013, 33(3): 362-367. DOI: 10.1111/liv.12038.
[32]	NORTHUP PG, FRIEDMAN LS, KAMATH PS. AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review[J]. Clin Gastroenterol Hepatol, 2019, 17(4): 595-606. DOI: 10.1016/j.cgh.2018.09.043.
[33]	O'SHEA RS, DAVITKOV P, KO CW, et al. AGA clinical practice guideline on the management of coagulation disorders in patients with cirrhosis[J]. Gastroenterology, 2021, 161(5): 1615-1627. e1. DOI: 10.1053/j.gastro.2021.08.015.
[34]	SCHIFFER CA, BOHLKE K, DELANEY M, et al. Platelet transfusion for patients with cancer: American Society of Clinical Oncology clinical practice guideline update[J]. J Clin Oncol, 2018, 36(3): 283-299. DOI: 10.1200/JCO.2017.76.1734.
[35]	KUTER DJ. Treatment of chemotherapy-induced thrombocytopenia in patients with non-hematologic malignancies[J]. Haematologica, 2022, 107(6): 1243-1263. DOI: 10.3324/haematol.2021.279512.
[36]	YANG G, HUANG R, YANG S, et al. Effect of postdose fasting duration on hetrombopag olamine pharmacokinetics and pharmacodynamics in healthy volunteers[J]. Br J Clin Pharmacol, 2020, 86(8): 1528-1536. DOI: 10.1111/bcp.14259.
[37]	TERRAULT N, CHEN YC, IZUMI N, et al. Avatrombopag before procedures reduces need for platelet transfusion in patients with chronic liver disease and thrombocytopenia[J]. Gastroenterology, 2018, 155(3): 705-718. DOI: 10.1053/j.gastro.2018.05.025.
[38]	AFDHAL NH, GIANNINI EG, TAYYAB G, et al. Eltrombopag before procedures in patients with cirrhosis and thrombocytopenia[J]. N Engl J Med, 2012, 367(8): 716-724. DOI: 10.1056/NEJMoa1110709.
[39]	MOUSSA MM, MOWAFY N. Preoperative use of romiplostim in thrombocytopenic patients with chronic hepatitis C and liver cirrhosis[J]. J Gastroenterol Hepatol, 2013, 28(2): 335-341. DOI: 10.1111/j.1440-1746.2012.07246.x.
[40]	LINDQUIST I, OLSON SR, LI A, et al. The efficacy and safety of thrombopoietin receptor agonists in patients with chronic liver disease undergoing elective procedures: a systematic review and meta-analysis[J]. Platelets, 2022, 33(1): 66-72. DOI: 10.1080/09537104.2020.1859102.
[41]	KUTER DJ. Milestones in understanding platelet production: a historical overview[J]. Br J Haematol, 2014, 165(2): 248-258. DOI: 10.1111/bjh.12781.
[42]	ZHANG J, ZHOU XM. Administration of recombinant human thrombopoietin before operation in patients with liver cirrhosis and hepatocellular carcinoma and thrombocytopenia[J]. J Prac Hepatol, 2020, 23(4): 552-555. DOI: 10.3969/j.issn.1672-5069.2020.04.025. 张静, 周新民. 应用重组人血小板生成素减少肝硬化患者术前血小板输注疗效初步研究[J]. 实用肝脏病杂志, 2020, 23(4): 552-555. DOI: 10.3969/j.issn.1672-5069.2020.04.025.
[43]	FENG R, LIU Y, ZHU XL, et al. Recombinant human thrombopoietin increases platelet count in severe thrombocytopenic patients with hepatitis B-related cirrhosis: Multicentre real-world observational study[J]. J Viral Hepat, 2022, 29(5): 306-316. DOI: 10.1111/jvh.13655.
[44]	Inc P. NEUMEGA Instrument[EB/OL]. https://www.pfizer.com/products/product-de-tail/neumega.
[45]	Qilu Pharmaceutical Co., Ltd. Package insert for recombinant human interleukin 11 for injection[EB/OL]. https://www.qilu-pharma.com/products_details/975814351594020864.html. 齐鲁制药有限公司. 注射用重组人白介素11说明书[EB/OL]. https://www.qilu-pharma.com/products_details/975814351594020864.html.
[46]	LIU BW, XIANG HL, LIANG J, et al. Comparison of the efficacy of recombinant human interleukin-11 and recombinant human thrombopoietin in the treating thrombocytopenia with hypersplenism in cirrhotic patients[J]. World Chin J Dig, 2016, 24(34): 4608-4614. DOI: 10.11569/wcjd.v24.i34.4608. 刘保文, 向慧玲, 梁静, 等. 重组人白介素-11及重组人血小板生成素在治疗肝硬化脾功能亢进所致血小板减少的疗效对比[J]. 世界华人消化杂志, 2016, 24(34): 4608-4614. DOI: 10.11569/wcjd.v24.i34.4608.
[47]	QIAN JD, YAO TT, WANG Y, et al. Management strategies for chronic liver disease-related thrombocytopenia[J]. Chin J Hepatol, 2021, 29(9): 896-899. DOI: 10.3760/cma.j.cn501113-20200609-00304. 钱建丹, 姚甜甜, 王艳, 等. 慢性肝病相关血小板减少症管理策略[J]. 中华肝脏病杂志, 2021, 29(9): 896-899. DOI: 10.3760/cma.j.cn501113-20200609-00304.
[48]	OGATA T, OKUDA K, SATO T, et al. Long-term outcome of splenectomy in advanced cirrhotic patients with hepatocellular carcinoma and thrombocytopenia[J]. Kurume Med J, 2013, 60(2): 37-45. DOI: 10.2739/kurumemedj.ms62010.
[49]	KIM NH, KIM HJ, CHO YK, et al. Long-term efficacy and safety of partial splenic embolization in hepatocellular carcinoma patients with thrombocytopenia who underwent transarterial chemoembolization[J]. J Korean Med Sci, 2019, 34(30): e208. DOI: 10.3346/jkms.2019.34.e208.
[50]	FENG K, MA K, LIU Q, et al. Randomized clinical trial of splenic radiofrequency ablation versus splenectomy for severe hypersplenism[J]. Br J Surg, 2011, 98(3): 354-361. DOI: 10.1002/bjs.7367.
[51]	SHI XB, FENG JK, WANG JH, et al. Does splenectomy significantly improve the prognosis of hepatocellular carcinoma patients with hypersplenism? A systematic review and meta-analysis[J]. Ann Transl Med, 2021, 9(8): 641. DOI: 10.21037/atm-20-6748.
[52]	WU Y, LI H, ZHANG T, et al. Splanchnic vein thrombosis in liver cirrhosis after splenectomy or splenic artery embolization: A Systematic Review and Meta-Analysis[J]. Adv Ther, 2021, 38(4): 1904-1930. DOI: 10.1007/s12325-021-01652-7.
[53]	WANG Q, DANG T, MENG X, et al. Is concomitant splenectomy necessary in radical gastric cancer surgery? A systematic review and meta-analysis[J]. Asia Pac J Clin Oncol, 2019, 15(2): e28-e35. DOI: 10.1111/ajco.13052.
[54]	WANG JX, WEI FX, XIE WQ, et al. Recent understandings of splenectomy for hypersplenism in patients with cirrhotic portal hypertension[J]. Chin J Gen Surg, 2022, 31 (1): 123-131. DOI: 10.7659/j.issn.1005-6947.2022.01.014. 王建雄, 魏丰贤, 谢文强, 等. 脾切除对肝硬化门静脉高压脾功能亢进患者影响的研究进展[J]. 中国普通外科杂志, 2022, 31(1): 123-131. DOI: 10.7659/j.issn.1005-6947.2022.01.014.
[55]	CAO SS, GUAN Y, ZHANG XF, et al. Literature analysis of adverse drug reaction induced by thrombopoietin receptor agonists[J]. Chin J Drug Appl Monit, 2022, 19(1): 34-38. DOI: 10.3969/j.issn.1672-8157.2022.01.010. 曹珊珊, 关月, 张筱芳, 等. 血小板生成素受体激动剂致不良反应的文献分析[J]. 中国药物应用与监测, 2022, 19(1): 34-38. DOI: 10.3969/j.issn.1672-8157.2022.01.010.
[56]	GHANIMA W, COOPER N, RODEGHIERO F, et al. Thrombopoietin receptor agonists: ten years later[J]. Haematologica, 2019, 104(6): 1112-1123. DOI: 10.3324/haematol.2018.212845.
[57]	HERMANN E, FERDJALLAH A. Eltrombopag-induced metabolic acidosis and hepatic encephalopathy in pediatric ITP[J]. J Pediatr Hematol Oncol, 2022, 44(2): e453-e455. DOI: 10.1097/MPH.0000000000002300.
[58]	Novartis Pharma Schwei AG. Instructions for Eltrombopag Olamine Tablets[EB/OL]. [2017-12-28]. https://zy.yaozh.com/instruct/sms20200619/2020060202.pdf.
[59]	XU WW, YANG L, GE JJ, et al. Comparison of Efficacy and Safety of rhIL-11 and rhTPO in the treatment of Thrombocytopenia caused by chemotherapy[J]. Systems Med, 2016, 1(12): 121-123. DOI: 10.19368/j.cnki.2096-1782.2016.12.121. 徐薇薇, 杨磊, 葛建娟, 等. rhIL-11及rhTPO用于化疗所致的血小板减少症的疗效及安全性对比[J]. 系统医学, 2016, 1(12): 121-123. DOI: 10.19368/j.cnki.2096-1782.2016.12.121.
[60]	YU J, DAI XF, LIU L, et al. Clinical studies of recombinant human thrombopoietin in treatment of gemzar and cisplatin-induced thrombocytopenia in patients with non-small cell lung cancer[J]. Chin J Cancer Prev Treat, 2009, 16(5): 374-376. https://www.cnki.com.cn/Article/CJFDTOTAL-QLZL200905019.htm 喻杰, 戴晓芳, 刘莉, 等. rhTPO和IL-11治疗NSCLC化疗后血小板减少症的临床观察[J]. 中华肿瘤防治杂志, 2009, 16(5): 374-376. https://www.cnki.com.cn/Article/CJFDTOTAL-QLZL200905019.htm
[61]	HOU M, LI M, JIN Z, et al. Post-marketing study of recombinant human thrombopoietin injection for adverse drug reaction monitoring[J]. Chin J New Drugs Clin Remed, 2015, 34(8): 642-646. DOI: 10.14109/j.cnki.xyylc.2015.08.018. 侯明, 李曼, 靳征. 重组人血小板生成素注射液上市后不良反应监测研究[J]. 中国新药与临床杂志, 2015, 34(8): 642-646. DOI: 10.14109/j.cnki.xyylc.2015.08.018.
[62]	DAI XF, YU J, LIU L, et al. Value of recombinant human thrombopoietin in the treatmeat of chemotherapy-induced thrombocytopenia in patients with solid tumor[J]. Chin J Oncol, 2008, 30(8): 623-625. DOI: 10.3321/j.issn:0253-3766.2008.08.016. 戴晓芳, 喻杰, 刘莉, 等. 重组人血小板生成素治疗化疗相关血小板减少的临床价值[J]. 中华肿瘤杂志, 2008, 30(8): 623-625. DOI: 10.3321/j.issn:0253-3766.2008.08.016.
[63]	CSCO Anti-Lymphoma Alliance, CACA Committee of Cancer Rehabilitation and Palliative Care, Haematology Branch of Chinese Medical Association. Chinese expert consensus on clinical application of recombinant human interleukin-11 in the treatment of thrombocytopenia (2018 edition)[J]. Chin Clin Oncol, 2018, 23(3): 260-266. DOI: 10.3969/j.issn.1009-0460.2018.03.014. 中国临床肿瘤学会抗淋巴瘤联盟, 中国抗癌协会癌症康复与姑息治疗专业委员会, 中华医学会血波学分会. 重组人白介素-11治疗血小板减少症临床应用中国专家共识(2018年版)[J]. 临床肿瘤学杂志, 2018, 23(3): 260-266. DOI: 10.3969/j.issn.1009-0460.2018.03.014.
[64]	TSOCHATZIS EA, SENZOLO M, GERMANI G, et al. Systematic review: portal vein thrombosis in cirrhosis[J]. Aliment Pharmacol Ther, 2010, 31(3): 366-374. DOI: 10.1111/j.1365-2036.2009.04182.x.
[65]	CHEN H, TRILOK G, WANG F, et al. A single hospital study on portal vein thrombosis in cirrhotic patients - clinical characteristics & risk factors[J]. Indian J Med Res, 2014, 139(2): 260-266.
[66]	FONT C, FARRU'S B, VIDAL L, et al. Incidental versus symptomatic venous thrombosis in cancer: a prospective observational study of 340 consecutive patients[J]. Ann Oncol, 2011, 22(9): 2101-2106. DOI: 10.1093/annonc/mdq720.
[67]	Hepatobiliary Disease Study Group, Chinese Society of Gastroenterology, Chinese Medical Association. Consensus for management of portal vein thrombosis in liver cirrhosis(2020, Shanghai)[J]. J Clin Hepatol, 2020, 36(12): 2667-2674. DOI: 10.3969/j.issn.1001-5256.2020.12.007. 中华医学会消化病学分会肝胆疾病学组. 肝硬化门静脉血栓管理专家共识(2020年, 上海)[J]. 临床肝胆病杂志, 2020, 36(12): 2667-2674. DOI: 10.3969/j.issn.1001-5256.2020.12.007.
[68]	FALANGA A, LEADER A, AMBAGLIO C, et al. EHA guidelines on management of antithrombotic treatments in thrombocytopenic patients with cancer[J]. Hemasphere, 2022, 6(8): e750. DOI: 10.1097/HS9.0000000000000750.
[69]	Guidelines Working Committee of Chinese Society of Clinical Oncology. Chinese Society of Clinical Oncology (CSCO) Guidelines for the Prevention and Treatment of Venous Thrombosis in Cancer Patients[M]. Beijing: People's Medical Publishing House, 2020. 中国临床肿瘤学会指南工作委员会. 中国临床肿瘤学会(CSCO)肿瘤患者静脉血栓防治指南2020[M]. 北京: 人民卫生出版社, 2020.
[70]	SHEN T, LIU Y, SHANG J, et al. Incidence and etiology of drug-induced liver injury in mainland China[J]. Gastroenterology, 2019, 156(8): 2230-2241. e11. DOI: 10.1053/j.gastro.2019.02.002.
[71]	RUBBIA-BRANDT L, AUDARD V, SARTORETTI P, et al. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer[J]. Ann Oncol, 2004, 15(3): 460-466. DOI: 10.1093/annonc/mdh095.
[72]	HE FL, MA L, LI YR, et al. Non-cirrhotic portal hypertension: the highlight of its diagnosis[J]. J Prac Hepatol, 2022, 25(1): 1-4. DOI: 10.3969/j.issn.1672-5069.2022.01.001. 何福亮, 马琳, 李悦榕, 等. 非肝硬化性门脉高压的临床诊断[J]. 实用肝脏病杂志, 2022, 25(1): 1-4. DOI: 10.3969/j.issn.1672-5069.2022.01.001.
[73]	de LÉDINGHEN V, VILLATE A, ROBIN M, et al. Sinusoidal obstruction syndrome[J]. Clin Res Hepatol Gastroenterol, 2020, 44(4): 480-485. DOI: 10.1016/j.clinre.2020.03.019.
[74]	ZHAO S, LAI RT, XIE Q. Diagnosis and clinical management of treatment-related toxicity with checkpoint inhibitors in hepatocellular carcinoma[J]. Chin J Hepatol, 2020, 25(5): 451-455. DOI: 10.3969/j.issn.1008-1704.2020.05.002. 赵爽, 赖荣陶, 谢青. 肝细胞癌免疫检查点抑制剂治疗相关毒性的诊断和临床管理[J]. 肝脏, 2020, 25(5): 451-455. DOI: 10.3969/j.issn.1008-1704.2020.05.002.
[75]	Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases. LiveTox: Clinical and research information on drug-induced liver injury[EB/OL]. [2017-6-1]. https://www.ncbi.nlm.nih.gov/books/NBK547897/.
[76]	MCDONALD GB, FRESTON JW, BOYER JL, et al. Liver complications following treatment of hematologic malignancy with anti-CD22-calicheamicin (Inotuzumab Ozogamicin)[J]. Hepatology, 2019, 69(2): 831-844. DOI: 10.1002/hep.30222.
[77]	JIANG LG, MENG HY, ZHANG HJ. Advances in research of radiation-induced liver damage[J]. World Chin J Dig, 2017, 25(20): 1811-1818. DOI: 10.11569/wcjd.v25.i20.1811. 江林宫, 孟鸿宇, 张火俊. 放射性肝损伤的研究进展[J]. 世界华人消化杂志, 2017, 25(20): 1811-1818. DOI: 10.11569/wcjd.v25.i20.1811.
[78]	WEYCKER D, HATFIELD M, GROSSMAN A, et al. Risk and consequences of chemotherapy-induced thrombocytopenia in US clinical practice[J]. BMC Cancer, 2019, 19(1): 151. DOI: 10.1186/s12885-019-5354-5.
[79]	CRIST M, HANSEN E, CHABLANI L, et al. Examining the bleeding incidences associated with targeted therapies used in metastatic renal cell carcinoma[J]. Crit Rev Oncol Hematol, 2017, 120: 151-162. DOI: 10.1016/j.critrevonc.2017.10.014.
[80]	CACA Professional Committee of Gynecological Oncology. Chinese expert consensus on ADR management of PARP inhibitors (2021 edition)[J]. Chin J Pract Gynecol Obstetr, 2021, 37(11): 1119-1130. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGSF202111011.htm 中国抗癌协会妇科肿瘤专业委员会. PARP抑制剂不良反应管理的中国专家共识(2021年版)[J]. 中国实用妇科与产科杂志, 2021, 37(11): 1119-1130. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGSF202111011.htm
[81]	HADDAD TC, ZHAO S, LI M, et al. Immune checkpoint inhibitor-related thrombocytopenia: incidence, risk factors and effect on survival[J]. Cancer Immunol Immunother, 2022, 71(5): 1157-1165. DOI: 10.1007/s00262-021-03068-2.
[82]	FU QC. Scoring system for diagnosis of drug-induced liver injuries[J]. J Prac Hepatol, 2014, 17(6): 569-571. DOI: 10.3969/j.issn.1672-5069.2014.06.003. 傅青春. 药物性肝损伤诊断的因果评分系统[J]. 实用肝脏病杂志, 2014, 17(6): 569-571. DOI: 10.3969/j.issn.1672-5069.2014.06.003.
[83]	Chinese Medical Association, Chinese Medical Association Publishing House, Chinese Society of Gastroenterology, et al. Guideline for primary care of drug-induced liver injury (2019)[J]. Chin J Gen Pract, 2020, 19(10): 868-875. DOI: 10.3760/cma.j.cn114798-20200812-00900. 中华医学会, 中华医学会杂志社, 中华医学会消化病学分会, 等. 药物性肝损伤基层诊疗指南(2019年)[J]. 中华全科医师杂志, 2020, 19(10): 868-875. DOI: 10.3760/cma.j.cn114798-20200812-00900.
[84]	BENCARDINO K, MAURI G, AMATU A, et al. Oxaliplatin immune-induced syndrome occurs with cumulative administration and rechallenge: Single institution series and systematic review study[J]. Clin Colorectal Cancer, 2016, 15(3): 213-221. DOI: 10.1016/j.clcc.2016.02.001.
[85]	JÁCOME AA, OHINATA A, MAHVASH A, et al. Bevacizumab does not influence the efficacy of partial splenic embolization in the management of chemotherapy-induced hypersplenism[J]. Clin Colorectal Cancer, 2020, 19(4): e189-e199. DOI: 10.1016/j.clcc.2020.04.007.
[86]	OVERMAN MJ, FERRAROTTO R, RAGHAV K, et al. The addition of bevacizumab to oxaliplatin-based chemotherapy: impact upon hepatic sinusoidal injury and thrombocytopenia[J]. J Natl Cancer Inst, 2018, 110(8): 888-894. DOI: 10.1093/jnci/djx288.
[87]	QDAISAT A, YEUNG SJ, ROJAS HERNANDEZ CH, et al. Characteristics and outcomes of intracranial hemorrhage in cancer patients visiting the emergency department[J]. J Clin Med, 2022, 11(3): 643. DOI: 10.3390/jcm11030643.