肝硬化凝血障碍机制的再认识

孙荣荣; 贺娜; 张粉娜; 张心怡; 王梓依; 王辉; 边娜娜; 闫红林

doi:10.12449/JCH240330

肝硬化凝血障碍机制的再认识

DOI: 10.12449/JCH240330

孙荣荣^{1, 2},
贺娜¹,
张粉娜¹,
张心怡²,
王梓依²,
王辉²,
边娜娜²,
闫红林^1, , ,

1.
西安医学院第一附属医院消化内科，西安 710077
2.
西安医学院研究生院，西安 710021

基金项目:

陕西省教育科学“十三五”规划课题 (SGH20Y1330);

佑安肝病传染病专科医疗联盟专项基金 (LM202003);

陕西基础科学（化学、生物学）研究院2022年度基础科学研究计划项目 (22JHQ09)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：孙荣荣负责设计论文框架，资料分析，起草论文；张心怡、王梓依、王辉、边娜娜负责文献收集；贺娜、张粉娜负责论文修改；贺娜、闫红林负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
闫红林， yanhonglin666@163.com （ORCID： 0009-0003-3060-7348）

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出版历程
- 收稿日期: 2023-07-16
- 录用日期: 2023-08-14
- 出版日期: 2024-03-20

Re-understanding of the mechanism of coagulation disorder in liver cirrhosis

1.
Department of Gastroenterology，The First Affiliated Hospital of Xi’an Medical College，Xi’an 710077，China
2.
Graduate School of Xi’an Medical University，Xi’an 710021，China

Research funding:

Shaanxi Provincial Education Science “13th Five-Year Plan” Project (SGH20Y1330);

Youan Specialist Medical Alliance for Liver and Infectious Diseases Special Fund (LM202003);

Shaanxi Institute of Basic Science （Chemistry and Biology） 2022 Basic Science Research Programme Projects (22JHQ09)

More Information

Corresponding author: YAN Honglin， yanhonglin666@163.com （ORCID： 0009-0003-3060-7348）

摘要

摘要: 肝脏在维持机体凝血和抗凝动态平衡中发挥重要调节作用。肝硬化患者抗凝与凝血的动态平衡很脆弱，会因凝血因子减少，血小板计数下降，纤溶亢进而增加出血风险，同时还会因血管性血友病因子、凝血因子Ⅷ升高，抗凝蛋白C、抗凝蛋白S降低，凝血酶生成潜力增加，抗纤溶成分的改变而形成血栓。本文对肝硬化凝血障碍的机制进行综述，以期对临床医生关于肝硬化患者的出血或血栓性疾病的预防和治疗提供帮助。
- 肝硬化 /
- 血液凝固 /
- 出血 /
- 血栓形成
Abstract: The liver plays an important regulatory role in maintaining the dynamic balance of coagulation and anticoagulation in the body. Such dynamic balance is fragile in patients with liver cirrhosis， and the risk of bleeding can be increased due to reductions in coagulation factors and platelet count and excessive fibrinolysis； meanwhile， thrombus can be formed due to the increases in von Willebrand factor and coagulation factor Ⅷ， the reductions in anticoagulant protein C and anticoagulant protein S， the increase in thrombin-generating potential， and alterations in antifibrinolytic components. This article reviews the mechanisms of coagulation disorder in liver cirrhosis， so as to help clinicians with the prevention and treatment of bleeding or thrombotic disorders in patients with liver cirrhosis.
- Liver Cirrhosis /
- Blood Coagulation /
- Haemorrhage /
- Thrombosis

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参考文献(34)

[1]	JIANG H, LI Y, SHENG Q, et al. Relationship between hepatitis B virus infection and platelet production and dysfunction[J]. Platelets, 2022, 33( 2): 212- 218. DOI: 10.1080/09537104.2021.2002836.
[2]	DAHAL S, UPADHYAY S, BANJADE R, et al. Thrombocytopenia in patients with chronic hepatitis C virus infection[J]. Mediterr J Hematol Infect Dis, 2017, 9( 1): e2017019. DOI: 10.4084/MJHID.2017.019.
[3]	SILCZUK A, HABRAT B. Alcohol-induced thrombocytopenia: Current review[J]. Alcohol, 2020, 86: 9- 16. DOI: 10.1016/j.alcohol.2020.02.166.
[4]	BASILI S, RAPARELLI V, NAPOLEONE L, et al. Platelet count does not predict bleeding in cirrhotic patients: results from the PRO-LIVER study[J]. Am J Gastroenterol, 2018, 113( 3): 368- 375. DOI: 10.1038/ajg.2017.457.
[5]	ZANETTO A, CAMPELLO E, BULATO C, et al. Increased platelet aggregation in patients with decompensated cirrhosis indicates higher risk of further decompensation and death[J]. J Hepatol, 2022, 77( 3): 660- 669. DOI: 10.1016/j.jhep.2022.03.009.
[6]	BASILI S, RAPARELLI V, RIGGIO O, et al. NADPH oxidase-mediated platelet isoprostane over-production in cirrhotic patients: implication for platelet activation[J]. Liver Int, 2011, 31( 10): 1533- 1540. DOI: 10.1111/j.1478-3231.2011.02617.x.
[7]	EGAN K, DILLON A, DUNNE E, et al. Increased soluble GPVI levels in cirrhosis: evidence for early in vivo platelet activation[J]. J Thromb Thrombolysis, 2017, 43( 1): 54- 59. DOI: 10.1007/s11239-016-1401-0.
[8]	MATSUI T, USUI M, WADA H, et al. Platelet activation assessed by glycoprotein vi/platelet ratio is associated with portal vein thrombosis after hepatectomy and splenectomy in patients with liver cirrhosis[J]. Clin Appl Thromb Hemost, 2018, 24( 2): 254- 262. DOI: 10.1177/1076029617725600.
[9]	CHEN SH, TSAI SC, LU HC. Platelets as a gauge of liver disease kinetics?[J]. Int J Mol Sci, 2022, 23( 19). DOI: 10.3390/ijms231911460.
[10]	TRIPODI A, PRIMIGNANI M, CHANTARANGKUL V, et al. An imbalance of pro-vs anti-coagulation factors in plasma from patients with cirrhosis[J]. Gastroenterology, 2009, 137( 6): 2105- 2111. DOI: 10.1053/j.gastro.2009.08.045.
[11]	POOTHONG J, POTTEKAT A, SIIRIN M, et al. Factor Ⅷ exhibits chaperone-dependent and glucose-regulated reversible amyloid formation in the endoplasmic reticulum[J]. Blood, 2020, 135( 21): 1899- 1911. DOI: 10.1182/blood.2019002867.
[12]	ZHANG K, WANG S, MALHOTRA J, et al. The unfolded protein response transducer IRE1α prevents ER stress-induced hepatic steatosis[J]. EMBO J, 2011, 30( 7): 1357- 1375. DOI: 10.1038/emboj.2011.52.
[13]	SINEGRE T, DURON C, LECOMPTE T, et al. Increased factor VIII plays a significant role in plasma hypercoagulability phenotype of patients with cirrhosis[J]. J Thromb Haemost, 2018, 16( 6): 1132- 1140. DOI: 10.1111/jth.14011.
[14]	TRIPODI A, PRIMIGNANI M, LEMMA L, et al. Evidence that low protein C contributes to the procoagulant imbalance in cirrhosis[J]. J Hepatol, 2013, 59( 2): 265- 270. DOI: 10.1016/j.jhep.2013.03.036.
[15]	SCHEINER B, BALCAR L, NUSSBAUMER RJ, et al. Factor VIII/protein C ratio independently predicts liver-related events but does not indicate a hypercoagulable state in ACLD[J]. J Hepatol, 2022, 76( 5): 1090- 1099. DOI: 10.1016/j.jhep.2021.12.038.
[16]	BOS S, van den BOOM B, KAMPHUISEN PW, et al. Haemostatic profiles are similar across all aetiologies of cirrhosis[J]. Thromb Haemost, 2019, 119( 2): 246- 253. DOI: 10.1055/s-0038-1676954.
[17]	TRIPODI A, PRIMIGNANI M, LEMMA L, et al. Detection of the imbalance of procoagulant versus anticoagulant factors in cirrhosis by a simple laboratory method[J]. Hepatology, 2010, 52( 1): 249- 255. DOI: 10.1002/hep.23653.
[18]	TAKAYA H, NAMISAKI T, ASADA S, et al. ADAMTS13, VWF, and endotoxin are interrelated and associated with the severity of liver cirrhosis via hypercoagulability[J]. J Clin Med, 2022, 11( 7): 1835. DOI: 10.3390/jcm11071835.
[19]	PÉPIN M, KLEINJAN A, HAJAGE D, et al. ADAMTS-13 and von Willebrand factor predict venous thromboembolism in patients with cancer[J]. J Thromb Haemost, 2016, 14( 2): 306- 315. DOI: 10.1111/jth.13205.
[20]	ZERMATTEN MG, FRAGA M, MORADPOUR D, et al. Hemostatic alterations in patients with cirrhosis: from primary hemostasis to fibrinolysis[J]. Hepatology, 2020, 71( 6): 2135- 2148. DOI: 10.1002/hep.31201.
[21]	KUME Y, IKEDA H, INOUE M, et al. Hepatic stellate cell damage may lead to decreased plasma ADAMTS13 activity in rats[J]. FEBS Lett, 2007, 581( 8): 1631- 1634. DOI: 10.1016/j.febslet.2007.03.029.
[22]	NIIYA M, UEMURA M, ZHENG XW, et al. Increased ADAMTS-13 proteolytic activity in rat hepatic stellate cells upon activation in vitro and in vivo[J]. J Thromb Haemost, 2006, 4( 5): 1063- 1070. DOI: 10.1111/j.1538-7836.2006.01893.x.
[23]	MANNUCCI PM, CAPOFERRI C, CANCIANI MT. Plasma levels of von Willebrand factor regulate ADAMTS-13, its major cleaving protease[J]. Br J Haematol, 2004, 126( 2): 213- 218. DOI: 10.1111/j.1365-2141.2004.05009.x.
[24]	LISMAN T, BONGERS TN, ADELMEIJER J, et al. Elevated levels of von Willebrand Factor in cirrhosis support platelet adhesion despite reduced functional capacity[J]. Hepatology, 2006, 44( 1): 53- 61. DOI: 10.1002/hep.21231.
[25]	SENZOLO M, COPPELL J, CHOLONGITAS E, et al. The effects of glycosaminoglycans on coagulation: a thromboelastographic study[J]. Blood Coagul Fibrinolysis, 2007, 18( 3): 227- 236. DOI: 10.1097/MBC.0b013e328010bd3d.
[26]	TRIPODI A. Detection of procoagulant imbalance. Modified endogenous thrombin potential with results expressed as ratio of values with-to-without thrombomodulin[J]. Thromb Haemost, 2017, 117( 5): 830- 836. DOI: 10.1160/TH16-10-0806.
[27]	KREMERS R, KLEINEGRIS MC, NINIVAGGI M, et al. Decreased prothrombin conversion and reduced thrombin inactivation explain rebalanced thrombin generation in liver cirrhosis[J]. PLoS One, 2017, 12( 5): e0177020. DOI: 10.1371/journal.pone.0177020.
[28]	WAN J, ROBERTS LN, HENDRIX W, et al. Whole blood thrombin generation profiles of patients with cirrhosis explored with a near patient assay[J]. J Thromb Haemost, 2020, 18( 4): 834- 843. DOI: 10.1111/jth.14751.
[29]	von MEIJENFELDT FA, LISMAN T. Fibrinolysis in patients with liver disease[J]. Semin Thromb Hemost, 2021, 47( 5): 601- 609. DOI: 10.1055/s-0040-1718924.
[30]	RIJKEN DC, KOCK EL, GUIMARãES AH, et al. Evidence for an enhanced fibrinolytic capacity in cirrhosis as measured with two different global fibrinolysis tests[J]. J Thromb Haemost, 2012, 10( 10): 2116- 2122. DOI: 10.1111/j.1538-7836.2012.04901.x.
[31]	PUNTER M, VOS BE, MULDER BM, et al. Poroelasticity of(bio)polymer networks during compression: theory and experiment[J]. Soft Matter, 2020, 16( 5): 1298- 1305. DOI: 10.1039/c9sm01973a.
[32]	DRIEVER EG, LISMAN T. Fibrin clot properties and thrombus composition in cirrhosis[J]. Res Pract Thromb Haemost, 2023, 7( 1): 100055. DOI: 10.1016/j.rpth.2023.100055.
[33]	HUGENHOLTZ GC, MACRAE F, ADELMEIJER J, et al. Procoagulant changes in fibrin clot structure in patients with cirrhosis are associated with oxidative modifications of fibrinogen[J]. J Thromb Haemost, 2016, 14( 5): 1054- 1066. DOI: 10.1111/jth.13278.
[34]	MARTINEZ J, MACDONALD KA, PALASCAK JE. The role of sialic acid in the dysfibrinogenemia associated with liver disease: distribution of sialic acid on the constituent chains[J]. Blood, 1983, 61( 6): 1196- 1202.