人工肝治疗的抗凝剂应用进展及选择策略

马元吉; 杜凌遥; 白浪; 唐红

doi:10.3969/j.issn.1001-5256.2022.10.038

人工肝治疗的抗凝剂应用进展及选择策略

DOI: 10.3969/j.issn.1001-5256.2022.10.038

四川大学华西医院感染性疾病中心，成都 610041

基金项目:

四川大学华西医院学科卓越发展1·3·5工程项目 (ZYGD20009);

四川大学华西医院学科卓越发展1·3·5工程项目 (ZYJC21014)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：马元吉起草并撰写文章主要内容；杜凌遥负责主要内容修改并予以完善；白浪负责设计文章思路并提出修改意见；唐红参与文章修改及审校。

详细信息

通信作者:
白浪，pangbailang@163.com

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出版历程
- 收稿日期: 2022-03-01
- 录用日期: 2022-04-08
- 出版日期: 2022-10-20

Anticoagulants for artificial liver support therapy: Application advances and selection strategies

Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China

Research funding:

1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (ZYGD20009);

1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (ZYJC21014)

More Information

Corresponding author: BAI Lang, pangbailang@163.com(ORCID: 0000-0001-5042-4336)

摘要

摘要: 凝血功能异常是肝衰竭的特征之一，患者体内的凝血功能趋于不稳定且脆弱的“再平衡”状态，易受内外因素影响而被打破。人工肝治疗肝衰竭时常需要使用抗凝剂，这可能打破“再平衡”，导致出血事件发生。本文综述了肝衰竭的凝血状态评估方法、可用抗凝剂的特点及其在人工肝治疗中的应用进展，并结合四川大学华西医院的选用经验，探讨人工肝治疗的抗凝管理与选择策略。
- 肝功能衰竭 /
- 肝, 人工 /
- 抗凝药 /
- 治疗学
Abstract: Coagulation disorder is one of the characteristics of liver failure, leading to an unstable and vulnerable "rebalance" state of coagulation function, which may be easily broken by internal or external factors. Anticoagulants are often required during artificial liver support therapy for patients with liver failure, which may break the "rebalance" state and result in bleeding events. This article reviews the methods for evaluating coagulation status in liver failure, the features of available anticoagulants, and the advances in the application of such anticoagulants in artificial liver support therapy and discusses the anticoagulation management and selection strategy for artificial liver support therapy with reference to the selection experience of West China Hospital of Sichuan University.
- Liver Failure /
- Liver, Artificial /
- Anticoagulants /
- Therapeutics

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图 1 人工肝治疗的抗凝管理流程图

Figure 1. Flow chart of anticoagulation management for artificial liver support system therapy

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图 2 华西医院人工肝治疗的抗凝选择路线图

Figure 2. Roadmap of anticoagulation selection for artificial liver support system therapy in West China Hospital

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表 1 人工肝治疗可用的抗凝剂及其特点

Table 1. Available anticoagulants and their characteristics for artificial liver support system therapy

抗凝剂	抗凝机制	拮抗剂	半衰期	主要代谢部位	绝对禁忌证	相对禁忌证	监测	增加出血风险
普通肝素	与AT-Ⅲ结合, 抑制凝血因子Ⅹa、Ⅱa、Ⅸa、Ⅺa、Ⅻa等; 抑制血小板的黏附聚集; 抗凝活性比Ⅹa: Ⅱa = 1: 1	鱼精蛋白: 中和100%	1 ~3 h	网状内皮系统	过敏、HIT、活动性出血.高危出血风险	严重肝功能障碍、AT-Ⅲ活性 < 50%	抗Ⅹa、APTT、ACT	+++
低分子肝素	与AT–Ⅲ结合, 抑制Ⅹa、Ⅱa; 抑制血小板的黏附聚集; 抗凝活性比Ⅹa: Ⅱa =2: 1 ~4: 1	鱼精蛋白: 中和50% ~60%	3 ~6 h	肾	过敏、HIT、活动性出血	严重肝功能障碍、AT -Ⅲ活性 < 50%、肌酐清除率 < 15~20 mL/ min	抗Ⅹa	++
磺达肝素	与AT–Ⅲ结合, 抑制Ⅹa; 抗凝活性比Ⅹa: Ⅱa =1:0	rFⅦa; 新鲜血浆(可能有效)	17~21 h	肾	过敏、活动性出血、肌酐清除率 < 20 mL/ min	肌酐清除率20~50 mL/min	抗Ⅹa	+
阿加曲班	高选择性凝血酶抑制剂, 抑制Ⅱa	PCC; 新鲜血浆(可能有效)	45 ~50 min	肝	过敏、活动性出血、高危出血风险、脑梗塞	严重肘功能障碍	APTT、ACT	+++
萘莫司他	丝氨酸蛋白酶抑制剂, 抑制Ⅱa、Ⅶa、Ⅹa、Ⅻa等	PCC; 新鲜血浆(可能有效)	8 ~10 min	羧酸酯酶(血液)肝	过敏、活动性出血	高钾血症	抗Ⅹa、APTT、ACT	+
枸橼酸钠	螯合离子钙	离子钙	5 min	线粒体: 肝(主要)、肾、肌、脑等	无	严重肝功能障碍、严重低氧血症和/或组织灌注不足、代谢性碱中毒/高钠血症	离子钙	无风险
无抗凝剂	生理盐水冲洗			肾	无	高危/极高危血栓形成风险、容量负荷过重者		无风险
注; 半衰期基于正常人体; 4T-Ⅲ, 抗疑血酶Ⅲ; rFⅦa, 重组人凝血因子Ⅶa; PCC, 凝血酶原复合物; HIT, 肝索相关性血小板减少症; APTT, 活化部分凝血活酶时向间; ACT, 活化凝血时间。

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