肝硬化止血再平衡的机制及输血、抗凝时机的选择
DOI: 10.3969/j.issn.1001-5256.2022.09.037
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:马欢负责撰写初稿;韩梅负责修改论文;张悦负责部分理论分析;姜春萌负责审校论文,提供理论指导;刘辉负责构思设计,审校论文。
Mechanism of rebalanced hemostasis in liver cirrhosis and the timing of blood transfusion and anticoagulation
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摘要: 肝硬化患者体内存在重建的止血再平衡,但此平衡状态不稳定,可轻易的被应激因素打破,导致出血或血栓形成。由于肝硬化止血再平衡复杂的发病机制,目前有限的监测和检查方法,以及临床医生的认识不足等原因,导致临床上缺乏预防和解决平衡状态被打破的有效策略。结合近年来的文献,本文总结了肝硬化止血再平衡的发生机制以及出血、血栓形成的原因,并讨论了输血与止血再平衡的关系以及血栓形成时抗凝药物的选择,为临床相关问题的解决提供了理论依据和新的思路。Abstract: Reconstructed rebalanced hemostasis exists in patients with liver cirrhosis, while such balance is unstable and can be easily broken by stress factors, which may lead to bleeding or thrombosis. There is a lack of effective strategies to prevent and solve the disrupted balance in clinic due to the complex pathogenesis of rebalanced hemostasis, limited testing methods, and insufficient awareness among clinicians. With reference to the articles in recent years, this article summarizes the mechanism of rebalanced hemostasis in liver cirrhosis and the causes of bleeding and thrombosis and discuss the association between blood transfusion and rebalanced hemostasis and the selection of anticoagulant drugs during thrombosis, in order to provide a theoretical basis and new ideas for solving related issues in clinical practice.
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Key words:
- Liver Cirrhosis /
- Hemorrhage /
- Blood Transfusion /
- Anticoagulants
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[1] TRIPODI A. Hemostasis abnormalities in cirrhosis[J]. Curr Opin Hematol, 2015, 22(5): 406-412. DOI: 10.1097/MOH.0000000000000164. [2] LISMAN T, PORTE RJ. Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences[J]. Blood, 2010, 116(6): 878-885. DOI: 10.1182/blood-2010-02-261891. [3] MCMURRY HS, JOU J, SHATZEL J. The hemostatic and thrombotic complications of liver disease[J]. Eur J Haematol, 2021, 107(4): 383-392. DOI: 10.1111/ejh.13688. [4] AREF S, MABED M, SELIM T. Thrombopoietin (TPO) levels in hepatic patients with thrombocytopenia[J]. Hematology, 2004, 9(5-6): 351-356. DOI: 10.1080/10245330400010620. [5] 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. [6] MITCHELL O, FELDMAN DM, DIAKOW M, et al. The pathophysiology of thrombocytopenia in chronic liver disease[J]. Hepat Med, 2016, 8: 39-50. DOI: 10.2147/HMER.S74612. [7] KUJOVICH JL. Coagulopathy in liver disease: a balancing act[J]. Hematology Am Soc Hematol Educ Program, 2015, 2015: 243-249. DOI: 10.1182/asheducation-2015.1.243. [8] 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. [9] DONG JF, MOAKE JL, NOLASCO L, et al. ADAMTS-13 rapidly cleaves newly secreted ultralarge von Willebrand factor multimers on the endothelial surface under flowing conditions[J]. Blood, 2002, 100(12): 4033-4039. DOI: 10.1182/blood-2002-05-1401. [10] FENG Y, LI X, XIAO J, et al. ADAMTS13: more than a regulator of thrombosis[J]. Int J Hematol, 2016, 104(5): 534-539. DOI: 10.1007/s12185-016-2091-2. [11] 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. [12] INTAGLIATA NM, DAVIS J, CALDWELL SH. Coagulation pathways, hemostasis, and thrombosis in liver failure[J]. Semin Respir Crit Care Med, 2018, 39(5): 598-608. DOI: 10.1055/s-0038-1673658. [13] TRIPODI A, PRIMIGNANI M, MANNUCCI PM, et al. Changing concepts of cirrhotic coagulopathy[J]. Am J Gastroenterol, 2017, 112(2): 274-281. DOI: 10.1038/ajg.2016.498. [14] WU X, YAO Z, ZHAO L, et al. Phosphatidylserine on blood cells and endothelial cells contributes to the hypercoagulable state in cirrhosis[J]. Liver Int, 2016, 36(12): 1800-1810. DOI: 10.1111/liv.13167. [15] LIAW PC, ITO T, IBA T, et al. DAMP and DIC: The role of extracellular DNA and DNA-binding proteins in the pathogenesis of DIC[J]. Blood Rev, 2016, 30(4): 257-261. DOI: 10.1016/j.blre.2015.12.004. [16] CHAPIN JC, HAJJAR KA. Fibrinolysis and the control of blood coagulation[J]. Blood Rev, 2015, 29(1): 17-24. DOI: 10.1016/j.blre.2014.09.003. [17] 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. [18] FERRO D, CELESTINI A, VIOLI F. Hyperfibrinolysis in liver disease[J]. Clin Liver Dis, 2009, 13(1): 21-31. DOI: 10.1016/j.cld.2008.09.008. [19] PECK-RADOSAVLJEVIC M. Thrombocytopenia in chronic liver disease[J]. Liver Int, 2017, 37(6): 778-793. DOI: 10.1111/liv.13317. [20] RODRÍGUEZ-CASTRO KI, ANTONELLO A, FERRARESE A. Spontaneous bleeding or thrombosis in cirrhosis: What should be feared the most?[J]. World J Hepatol, 2015, 7(14): 1818-1827. DOI: 10.4254/wjh.v7.i14.1818. [21] TRIPODI A, ANSTEE QM, SOGAARD KK, et al. Hypercoagulability in cirrhosis: causes and consequences[J]. J Thromb Haemost, 2011, 9(9): 1713-1723. DOI: 10.1111/j.1538-7836.2011.04429.x. [22] MA SD, WANG J, BEZINOVER D, et al. Inherited thrombophilia and portal vein thrombosis in cirrhosis: A systematic review and meta-analysis[J]. Res Pract Thromb Haemost, 2019, 3(4): 658-667. DOI: 10.1002/rth2.12253. [23] ZHAN XL, JI Y, WANG YD. Laparoscopic splenectomy for hypersplenism secondary to liver cirrhosis and portal hypertension[J]. World J Gastroenterol, 2014, 20(19): 5794-5800. DOI: 10.3748/wjg.v20.i19.5794. [24] 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. [25] HUANG D, TAO M, CAO L, et al. Risk factors and anticoagulation effects of portal vein system thrombosis after laparoscopic splenectomy in patients with or without cirrhosis[J]. Surg Laparosc Endosc Percutan Tech, 2019, 29(6): 498-502. DOI: 10.1097/SLE.0000000000000710. [26] STRAVITZ RT. Algorithms for managing coagulation disorders in liver disease[J]. Hepatol Int, 2018, 12(5): 390-401. DOI: 10.1007/s12072-018-9886-6. [27] LEBRETON A, SINEGRE T, LECOMPTE T, et al. Thrombin generation and cirrhosis: state of the art and perspectives[J]. Semin Thromb Hemost, 2020, 46(6): 693-703. DOI: 10.1055/s-0040-1715102. [28] 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. [29] ROBERTS LN, PATEL RK, ARYA R. Haemostasis and thrombosis in liver disease[J]. Br J Haematol, 2010, 148(4): 507-521. DOI: 10.1111/j.1365-2141.2009.08021.x. [30] THAI C, OBEN C, WAGENER G. Coagulation, hemostasis, and transfusion during liver transplantation[J]. Best Pract Res Clin Anaesthesiol, 2020, 34(1): 79-87. DOI: 10.1016/j.bpa.2020.03.002. [31] 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. [32] VON MEIJENFELDT FA, VAN DEN BOOM BP, ADELMEIJER J, et al. Prophylactic fresh frozen plasma and platelet transfusion have a prothrombotic effect in patients with liver disease[J]. J Thromb Haemost, 2021, 19(3): 664-676. DOI: 10.1111/jth.15185. [33] LIU P, HUM J, JOU J, et al. Transfusion strategies in patients with cirrhosis[J]. Eur J Haematol, 2020, 104(1): 15-25. DOI: 10.1111/ejh.13342. [34] RASSI AB, D'AMICO EA, TRIPODI A, et al. Fresh frozen plasma transfusion in patients with cirrhosis and coagulopathy: Effect on conventional coagulation tests and thrombomodulin-modified thrombin generation[J]. J Hepatol, 2020, 72(1): 85-94. DOI: 10.1016/j.jhep.2019.09.008. [35] DROLZ A, HORVATITS T, ROEDL K, et al. Coagulation parameters and major bleeding in critically ill patients with cirrhosis[J]. Hepatology, 2016, 64(2): 556-568. DOI: 10.1002/hep.28628. [36] PANT A, KOPEC AK, LUYENDYK JP. Role of the blood coagulation cascade in hepatic fibrosis[J]. Am J Physiol Gastrointest Liver Physiol, 2018, 315(2): G171-G176. DOI: 10.1152/ajpgi.00402.2017. [37] FLORES B, TRIVEDI HD, ROBSON SC, et al. Hemostasis, bleeding and thrombosis in liver disease[J]. J Transl Sci, 2017, 3(3): 10.15761/JTS. 1000182. DOI: 10.15761/JTS.1000182. [38] WITT DM, CLARK NP, KAATZ S, et al. Guidance for the practical management of warfarin therapy in the treatment of venous thromboembolism[J]. J Thromb Thrombolysis, 2016, 41(1): 187-205. DOI: 10.1007/s11239-015-1319-y. [39] INTAGLIATA NM, HENRY ZH, MAITLAND H, et al. Direct oral anticoagulants in cirrhosis patients pose similar risks of bleeding when compared to traditional anticoagulation[J]. Dig Dis Sci, 2016, 61(6): 1721-1727. DOI: 10.1007/s10620-015-4012-2. [40] DE GOTTARDI A, TREBICKA J, KLINGER C, et al. Antithrombotic treatment with direct-acting oral anticoagulants in patients with splanchnic vein thrombosis and cirrhosis[J]. Liver Int, 2017, 37(5): 694-699. DOI: 10.1111/liv.13285. [41] CHUN HS, CHOE AR, LEE M, et al. Treatment of direct oral anticoagulants in patients with liver cirrhosis and portal vein thrombosis[J]. Clin Mol Hepatol, 2021, 27(4): 535-552. DOI: 10.3350/cmh.2021.0109. [42] LEONARDI F, MARIA N, VILLA E. Anticoagulation in cirrhosis: a new paradigm?[J]. Clin Mol Hepatol, 2017, 23(1): 13-21. DOI: 10.3350/cmh.2016.0110. [43] ZHANG N, YAO Y, XUE W, et al. Early prophylactic anticoagulation for portal vein system thrombosis after splenectomy: A systematic review and meta-analysis[J]. Biomed Rep, 2016, 5(4): 483-490. DOI: 10.3892/br.2016.755. [44] KAWANAKA H, AKAHOSHI T, KINJO N, et al. Impact of antithrombin Ⅲ concentrates on portal vein thrombosis after splenectomy in patients with liver cirrhosis and hypersplenism[J]. Ann Surg, 2010, 251(1): 76-83. DOI: 10.1097/SLA.0b013e3181bdf8ad. [45] GONG C, QIN X, YANG J, et al. The best anticoagulation strategy for cirrhotic patients who underwent splenectomy: A network meta-analysis[J]. Gastroenterol Res Pract, 2017, 2017: 9216172. DOI: 10.1155/2017/9216172.
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