人工肝支持系统治疗肝衰竭伴血小板减少的机制、风险及管理策略

马茹; 王志伟; 马立; 丁子惠; 李星宇; 王艳

doi:10.12449/JCH260732

人工肝支持系统治疗肝衰竭伴血小板减少的机制、风险及管理策略

DOI: 10.12449/JCH260732

山西医科大学第三医院（山西白求恩医院，山西医学科学院，同济山西医院）感染病科，太原 030032

基金项目:

北京肝胆相照公益基金会人工肝专项基金 (iGandanF-1082023-RGG030);

山西省基础研究计划项目 (202403021211104)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：马茹负责设计论文框架，起草论文；王志伟、马立和丁子惠负责查找资料，绘制图表；李星宇负责拟定写作思路；王艳负责指导撰写文章并最后定稿。

详细信息

通信作者:
王艳， wangyan@sxbqeh.com.cn （ORCID： 0000-0002-1725-589X）

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出版历程
- 收稿日期: 2025-11-27
- 录用日期: 2026-01-28
- 出版日期: 2026-07-25

Mechanisms, risks, and management strategies of artificial liver support system in treating liver failure with thrombocytopenia

Department of Infectious Diseases，Third Hospital of Shanxi Medical University，Shanxi Bethune Hospital，Shanxi Academy of Medical Sciences，Tongji Shanxi Hospital，Taiyuan 030032，China

Research funding:

Artificial Liver Special Fund,Beijing GANDAN Xiangzhao Public Welfare Foundation (iGandanF-1082023-RGG030);

Foundamental Research Program of Shanxi Province (202403021211104)

More Information

Corresponding author: Wang Yan， wangyan@sxbqeh.com.cn （ORCID： 0000-0002-1725-589X）

摘要

摘要: 人工肝支持系统治疗肝衰竭常并发血小板减少，增加出血风险。本文系统阐述血小板在肝病中的病理生理作用，系统分析不同人工肝支持系统模式对血小板的差异影响，重点关注生物相容性、抗凝策略等环节，总结个体化血小板输注、促血小板生成药物应用等管理策略，并论证血小板计数作为治疗安全性与疗效预测指标的价值，以期为临床精准干预提供依据。
- 肝功能衰竭 /
- 肝，人工 /
- 血小板减少
Abstract: Artificial liver support therapy for liver failure is often complicated by thrombocytopenia， which increases the risk of bleeding. This article systematically elaborates on the pathophysiological role of platelets in liver disease， and systematically analyzes the differential effect of various artificial liver support modalities on platelets， with a focus on key factors such as biocompatibility and anticoagulation strategies. This article also summarizes the clinical management approaches including individualized platelet transfusion and the application of thrombopoietic agents and discusses the value of platelet count as a predictive indicator for treatment safety and efficacy， in order to provide a basis for precise clinical intervention.
- Liver Failure /
- Liver， Artificial /
- Thrombocytopenia

HTML全文

注： ALSS，人工肝支持系统；DPMAS，双重血浆分子吸附系统；PE，血浆置换；MARS，分子吸附再循环系统；TPO-RA，血小板生成素受体激动剂；RCA，局部枸橼酸抗凝；NM，甲磺酸萘莫司他。

图 1 人工肝支持治疗相关血小板减少的机制与管理策略

Figure 1. Mechanisms and management strategies of thrombocytopenia associated with artificial liver support therapy

下载: 全尺寸图片幻灯片

参考文献(45)

[1]	Hernaez R, Solà E, Moreau R, et al. Acute-on-chronic liver failure: An update[J]. Gut, 2017, 66( 3): 541- 553. DOI: 10.1136/gutjnl-2016-312670.
[2]	Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, Chinese Medical Association; Expert Committee of Liver Failure and Artificial Liver, Chinese Society of Infectious Diseases, Chinese Medical Association; National Clinical Research Center for Infectious Diseases, et al. Guidelines on application of artificial liver blood purification system(version 2023)[J]. Chin J Clin Infect Dis, 2023, 16( 6): 401- 411. DOI: 10.3760/cma.j.issn.1674-2397.2023.06.001. 中华医学会感染病学分会肝衰竭与人工肝学组, 中华医学会感染病学分会肝衰竭与人工肝专家委员会, 国家感染性疾病临床医学研究中心, 等. 人工肝血液净化系统治疗指南(2023年版)[J]. 中华临床感染病杂志, 2023, 16( 6): 401- 411. DOI: 10.3760/cma.j.issn.1674-2397.2023.06.001.
[3]	Schönfelder K, Hirsch L K, Kribben A, et al. Artificial liver support with Cytosorb and continuous veno-venous hemodiafiltration versus advanced organ support(ADVOS) for critically ill patients with hyperbilirubinemia and acute-on-chronic liver failure(ACLF)[J]. BMC Nephrol, 2025, 26( 1): 432. DOI: 10.1186/s12882-025-04342-6.
[5]	Nicolai L, Pekayvaz K, Massberg S. Platelets: Orchestrators of immunity in host defense and beyond[J]. Immunity, 2024, 57( 5): 957- 972. DOI: 10.1016/j.immuni.2024.04.008.
[6]	National Clinical Research Center for Infectious Diseases; Society of Hepatology, Beijing Medical Association; Translational Medicine Branch, Chinese Association of Gerontology and Geriatrics. Chinese expert consensus on clinical management of hepatopathy-related thrombocytopenia[J]. J Clin Hepatol, 2023, 39( 10): 2307- 2320. DOI: 10.3969/j.issn.1001-5256.2023.10.007. 国家感染性疾病临床医学研究中心, 北京医学会肝病学分会, 中国老年学和老年医学学会转化医学分会. 肝病相关血小板减少症临床管理中国专家共识[J]. 临床肝胆病杂志, 2023, 39( 10): 2307- 2320. DOI: 10.3969/j.issn.1001-5256.2023.10.007.
[7]	Zanetto A, Toffanin S, Campello E, et al. Reticulated platelets are increased and hyper-activated in patients with cirrhosis, especially those with poor outcome[J]. Dig Liver Dis, 2024, 56( 8): 1327- 1334. DOI: 10.1016/j.dld.2024.03.007.
[8]	Lecchi A, Tosetti G, Ghali C, et al. Comprehensive investigation of platelet function in patients with cirrhosis[J]. Thromb Res, 2024, 237: 64- 70. DOI: 10.1016/j.thromres.2024.03.017.
[9]	Kaiser R, Escaig R, Nicolai L. Hemostasis without clot formation: How platelets guard the vasculature in inflammation, infection, and malignancy[J]. Blood, 2023, 142( 17): 1413- 1425. DOI: 10.1182/blood.2023020535.
[10]	Weigel C, Bellaci J, Spiegel S. Sphingosine-1-phosphate and its receptors in vascular endothelial and lymphatic barrier function[J]. J Biol Chem, 2023, 299( 6): 104775. DOI: 10.1016/j.jbc.2023.104775.
[11]	del Gaudio I, Nitzsche A, Boyé K, et al. Zonation and ligand and dose dependence of sphingosine 1-phosphate receptor-1 signalling in blood and lymphatic vasculature[J]. Cardiovasc Res, 2024, 120( 14): 1794- 1810. DOI: 10.1093/cvr/cvae168.
[12]	European Association for the Study of the Liver. EASL clinical practice guidelines on prevention and management of bleeding and thrombosis in patients with cirrhosis[J]. J Hepatol, 2022, 76( 5): 1151- 1184. DOI: 10.1016/j.jhep.2021.09.003.
[13]	Dalbeni A, Castelli M, Zoncapè M, et al. Platelets in non-alcoholic fatty liver disease[J]. Front Pharmacol, 2022, 13: 842636. DOI: 10.3389/fphar.2022.842636.
[14]	Maeda Y, Watanabe Y, Ishikawa N, et al. Platelet-rich plasma-derived extracellular vesicles improve liver cirrhosis in mice[J]. Regen Ther, 2024, 26: 1048- 1057. DOI: 10.1016/j.reth.2024.10.010.
[15]	Monet C, de Jong A, Aarab Y, et al. Adverse events, short- and long-term outcomes of extra corporeal liver therapy in the intensive care unit: 16 years experience with MARS® in a single center[J]. Crit Care, 2022, 26( 1): 282. DOI: 10.1186/s13054-022-04165-z.
[16]	Yoo S W, Ki M J, Kim D, et al. Bleeding complications associated with the molecular adsorbent recirculating system: A retrospective study[J]. Acute Crit Care, 2021, 36( 4): 322- 331. DOI: 10.4266/acc.2021.00276.
[17]	Jia Jinfeng, Liang Fei, Huang Jianwei, et al. Effect of artificial liver with double plasma molecular absorb system model on patients' platelets and corresponding treatment strategy[J]. J Peking Univ Heal Sci, 2022, 54( 3): 548- 551. DOI: 10.19723/j.issn.1671-167X.2022.03.022. 贾金凤, 梁菲, 黄建伟, 等. 双重血浆分子吸附系统模式人工肝治疗对血小板的影响[J]. 北京大学学报(医学版), 2022, 54( 3): 548- 551. DOI: 10.19723/j.issn.1671-167X.2022.03.022.
[18]	Dai Mei, Shen Youshu, Zhao Fei, et al. Effect of plasma replacement combined with dual plasma adsorption mode artificial liver therapy on fibrinogen[J]. Chin Hepatol, 2023, 28( 5): 523- 526. DOI: 10.3969/j.issn.1008-1704.2023.05.007. 代梅, 申友书, 赵菲, 等. 血浆置换联合双重血浆吸附模式人工肝治疗对纤维蛋白原的影响[J]. 肝脏, 2023, 28( 5): 523- 526. DOI: 10.3969/j.issn.1008-1704.2023.05.007.
[19]	Haselwanter P, Scheiner B, Balcar L, et al. Use of the CytoSorb adsorber in patients with acute-on-chronic liver failure[J]. Sci Rep, 2024, 14: 11309. DOI: 10.1038/s41598-024-61658-3.
[20]	Papamichalis P, Oikonomou K G, Valsamaki A, et al. Liver replacement therapy with extracorporeal blood purification techniques current knowledge and future directions[J]. World J Clin Cases, 2023, 11( 17): 3932- 3948. DOI: 10.12998/wjcc.v11.i17.3932.
[21]	NALESSO F, BETTIN E, BOGO M, et al. Renal replacement therapy combined with artificial or bioartificial liver support system[M]// Nutrition, Metabolism and Kidney Support. Cham: Springer Nature Switzerland, 2024: 595- 609.
[22]	ISO 10993-4: 2017 Biological evaluation of medical devices-Part 4: Selection of tests for interactions with blood[S].
[23]	Zhang L Q, Liu G H, Xia Q P, et al. Research progress on blood compatibility of hemoperfusion adsorbent materials[J]. Front Bioeng Biotechnol, 2024, 12: 1456694. DOI: 10.3389/fbioe.2024.1456694.
[24]	Damianaki A, Stambolliu E, Alexakou Z, et al. Expanding the potential therapeutic options of hemoperfusion in the era of improved sorbent biocompatibility[J]. Kidney Res Clin Pract, 2023, 42( 3): 298- 311. DOI: 10.23876/j.krcp.22.223.
[25]	Can E G, Eskizengin H. Recent updates on blood purification: Use of smart polymer materials[J]. J Biomed Mater Res A, 2025, 113( 3): e37883. DOI: 10.1002/jbm.a.37883.
[26]	Su R, Liu W, Shi G, et al. A superior material with antithrombotic properties serves as a secure adsorbent for the elimination of bilirubin in vitro and in pig models[J]. Chem Eng J, 2024, 499: 156533. DOI: 10.1016/j.cej.2024.156533.
[27]	Wang Y L, Wang S S, He X Q, et al. A breakthrough trial of an artificial liver without systemic heparinization in hyperbilirubinemia beagle models[J]. Bioact Mater, 2023, 20: 651- 662. DOI: 10.1016/j.bioactmat.2022.06.019.
[28]	Fisher R, Moore G W, Mitchell M J, et al. Effects of regional citrate anticoagulation on thrombin generation, fibrinolysis and platelet function in critically ill patients receiving continuous renal replacement therapy for acute kidney injury: A prospective study[J]. Ann Intensive Care, 2022, 12( 1): 29. DOI: 10.1186/s13613-022-01004-w.
[29]	Jiao J, Yu Y, Wei S J, et al. Heparin anticoagulation versus regional citrate anticoagulation for membrane therapeutic plasma exchange in patients with increased bleeding risk[J]. Ren Fail, 2023, 45( 1): 2210691. DOI: 10.1080/0886022X.2023.2210691.
[30]	Hu F, Sun Y L, Bai K, et al. Clinical application of regional citrate anticoagulation for continuous renal replacement therapy in children with liver injury[J]. Front Pediatr, 2022, 10: 847443. DOI: 10.3389/fped.2022.847443.
[31]	Peng B, Lu J Q, Guo H B, et al. Regional citrate anticoagulation for replacement therapy in patients with liver failure: A systematic review and meta-analysis[J]. Front Nutr, 2023, 10: 1031796. DOI: 10.3389/fnut.2023.1031796.
[32]	Ren S, Huang L M, Li Y, et al. Comparison of efficacy and safety of different anticoagulation regimens in plasma exchange: A systematic review and meta-analysis[J]. PLoS One, 2024, 19( 10): e0311603. DOI: 10.1371/journal.pone.0311603.
[33]	Lang Y H, Zheng Y, Qi B C, et al. Anticoagulation with nafamostat mesilate during extracorporeal life support[J]. Int J Cardiol, 2022, 366: 71- 79. DOI: 10.1016/j.ijcard.2022.07.022.
[34]	Sun X K, Wang F, Chen Z W, et al. Integrative anticoagulation of nafamostat mesylate in double plasma molecular adsorption system plus sequential half-dose plasmapheresis for patients with liver failure: A randomised controlled trial protocol[J]. BMJ Open, 2025, 15( 2): e098898. DOI: 10.1136/bmjopen-2025-098898.
[35]	Zeng Junjie, Zhong Lincui, Peng Enlan, et al. The influence of different placement time on the monitoring of anticoagulation strength of blood samples after adding naph-thalmostat mesylate in vitro[J]. Chin J Med Offic, 2024, 52( 7): 671- 673, 677. DOI: 10.16680/j.1671-3826.2024.07.03. 曾俊杰, 钟林翠, 彭恩兰, 等. 体外加入甲磺酸萘莫司他后血标本不同放置时间对其抗凝强度监测影响[J]. 临床军医杂志, 2024, 52( 7): 671- 673, 677. DOI: 10.16680/j.1671-3826.2024.07.03.
[36]	Biolato M, Vitale F, Galasso T, et al. Minimum platelet count threshold before invasive procedures in cirrhosis: Evolution of the guidelines[J]. World J Gastrointest Surg, 2023, 15( 2): 127- 141. DOI: 10.4240/wjgs.v15.i2.127.
[37]	Kumar R, Ng L X L, Wong Y J, et al. Rotational thromboelastometry reduces the need for preemptive transfusion in cirrhosis: A randomized controlled trial(NCT: 05698134)[J]. J Clin Exp Hepatol, 2025, 15( 1): 102409. DOI: 10.1016/j.jceh.2024.102409.
[38]	Satapathy S K, Sundaram V, Shiffman M L, et al. Real-world use of avatrombopag in patients with chronic liver disease and thrombocytopenia undergoing a procedure[J]. Medicine, 2023, 102( 40): e35208. DOI: 10.1097/MD.0000000000035208.
[39]	Wang Y S, Wang W, Zhang S, et al. Clinical efficacy of avatrombopag and recombinant human thrombopoietin in the treatment of chronic liver disease-associated severe thrombocytopenia: A real-world study[J]. Front Pharmacol, 2022, 13: 1009612. DOI: 10.3389/fphar.2022.1009612.
[40]	Yoshiji H, Suzuki J, Imasaki M, et al. Safety and effectiveness of lusutrombopag in patients who have chronic liver disease with thrombocytopenia and undergoing invasive procedures: Real-world post-marketing surveillance in Japan[J]. Hepatol Res, 2023, 53( 11): 1105- 1116. DOI: 10.1111/hepr.13945.
[41]	Gallo P, de Vincentis A, Terracciani F, et al. Final results from the first European real-world experience on lusutrombopag treatment in cirrhotic patients with severe thrombocytopenia: Insights from the REAl-world lusutrombopag treatment in ITalY study[J]. J Clin Med, 2024, 13( 13): 3965. DOI: 10.3390/jcm13133965.
[42]	Niu L Y, Zhou J M, Zhao N H, et al. Safety and efficacy of DPMAS in patients with acute-on-chronic liver failure based on different platelet count levels[J]. J Clin Apher, 2025, 40( 1): e70006. DOI: 10.1002/jca.70006.
[43]	Ouyang R J, Li H, Xia J, et al. Lower platelet counts were associated with 90-day adverse outcomes in acute-on-chronic liver disease patients[J]. Ann Palliat Med, 2021, 10( 9): 9342- 9353. DOI: 10.21037/apm-21-1019.
[44]	Li Shoujuan, Wang Li, Zhou Ming, et al. Efficacy and safety of artificial liver support therapy with a selective plasma separator in low-platelet count patients with acute-on-chronic liver failure[J]. J Clin Hepatol, 2024, 40( 6): 1191- 1195. DOI: 10.12449/JCH240619. 李守娟, 王丽, 周明, 等. 经选择性血浆分离器行人工肝治疗低血小板计数慢加急性肝衰竭患者的效果及安全性分析[J]. 临床肝胆病杂志, 2024, 40( 6): 1191- 1195. DOI: 10.12449/JCH240619.
[45]	Li X, Li H, Zhu Y C, et al. PLT counts as a predictive marker after plasma exchange in patients with hepatitis B virus-related acute-on-chronic liver failure[J]. J Clin Med, 2023, 12( 3): 851. DOI: 10.3390/jcm12030851.
[46]	Ma Y J, Xu Y, Du L Y, et al. Outcome of patients with different stages of acute-on-chronic liver failure treated with artificial liver support system[J]. Front Med, 2024, 11: 1381386. DOI: 10.3389/fmed.2024.1381386.