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DOI: 10.1055/s-0040-1722192
Anticoagulant Treatment for Splanchnic Vein Thrombosis in Liver Cirrhosis: A Systematic Review and Meta-Analysis
Abstract
Background Splanchnic vein thrombosis (SVT) is a common complication in patients with liver cirrhosis. The aim of this study was to evaluate the efficacy and safety of anticoagulant therapy for SVT in cirrhotic patients.
Methods In this systematic review and meta-analysis, studies reporting on SVT recanalization and progression, recurrent venous thromboembolism (VTE), major bleeding, and overall mortality were searched in MEDLINE, EMBASE, and ClinicalTrial.gov up to December 2019. Pooled proportions and risk ratios (RRs) with corresponding 95% confidence intervals (CIs) were calculated.
Results A total of 1,475 patients were included in 26 studies (23 observational and 3 randomized controlled trials). In patients receiving anticoagulant therapy, SVT recanalization occurred in 68% (95% CI, 62–74; 571/842 patients; 22 studies), SVT progression in 6% (95% CI, 4–9; 25/748 patients; 22 studies), recurrent VTE in 10% (95% CI, 4–22; 48/399 patients; 7 studies), major bleeding in 6% (95% CI, 4–10; 58/785 patients; 18 studies), and overall mortality in 9% (95% CI, 6–14; 68/787 patients; 17 studies). Anticoagulant treatment was associated with higher SVT recanalization (RR 3.19; 95% CI, 1.42–7.17), lower thrombosis progression (RR 0.28; 95% CI, 0.15–0.52), major bleeding (RR 0.52; 95% CI, 0.28–0.97), and overall mortality (RR 0.42; 95% CI, 0.24–0.73) compared with no treatment.
Conclusion Anticoagulant therapy seems to improve vein recanalization and to reduce SVT progression, major bleeding, and overall mortality in cirrhotic patients with SVT. The incidence of recurrent VTE during anticoagulation remains substantial.
Authors' Contributions
Study conception and design: E.V., M.D.N., N.R., W.A.; Data acquisition: E.V., O.C., M.D.N., N.R.; Statistical analysis: E.V., M.D.N., N.R.; Interpretation of the data: All authors; Drafting of the manuscript: E.V., M.D.N., N.R., W.A.; Critical revision of the manuscript for important intellectual content: All authors; Final approval of the manuscript: All authors.
Publikationsverlauf
Eingereicht: 22. Juni 2020
Angenommen: 17. November 2020
Artikel online veröffentlicht:
01. Februar 2021
© 2021. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
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References
- 1 Intagliata NM, Argo CK, Stine JG, Lisman T, Caldwell SH, Violi F. Concepts and controversies in haemostasis and thrombosis associated with liver disease: Proceedings of the 7th International Coagulation in Liver Disease Conference. Thromb Haemost 2018; 118 (08) 1491-1506
- 2 Nery F, Chevret S, Condat B. et al; Groupe d'Etude et de Traitement du Carcinome Hépatocellulaire. Causes and consequences of portal vein thrombosis in 1,243 patients with cirrhosis: results of a longitudinal study. Hepatology 2015; 61 (02) 660-667
- 3 Intagliata NM, Caldwell SH, Tripodi A. Diagnosis, development, and treatment of portal vein thrombosis in patients with and without cirrhosis. Gastroenterology 2019; 156 (06) 1582-1599
- 4 Tripodi A, Primignani M, Chantarangkul V. et al. An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis. Gastroenterology 2009; 137 (06) 2105-2111
- 5 La Mura V, Tripodi A, Tosetti G. et al. Resistance to thrombomodulin is associated with de novo portal vein thrombosis and low survival in patients with cirrhosis. Liver Int 2016; 36 (09) 1322-1330
- 6 Zermatten MG, Fraga M, Moradpour D. et al. Haemostatic alterations in cirrhotic patients: from primary haemostasis to fibrinolysis. Hepatology 2020
- 7 D'Amico G, Pagliaro L, Bosch J. The treatment of portal hypertension: a meta-analytic review. Hepatology 1995; 22 (01) 332-354
- 8 Loffredo L, Pastori D, Farcomeni A, Violi F. Effects of anticoagulants in patients with cirrhosis and portal vein thrombosis: a systematic review and meta-analysis. Gastroenterology 2017; 153 (02) 480-487
- 9 Qi X, De Stefano V, Li H, Dai J, Guo X, Fan D. Anticoagulation for the treatment of portal vein thrombosis in liver cirrhosis: a systematic review and meta-analysis of observational studies. Eur J Intern Med 2015; 26 (01) 23-29
- 10 Pettinari I, Vukotic R, Stefanescu H. et al; BO-LIVES (BOlogna LIVEr vascular Studies). Clinical impact and safety of anticoagulants for portal vein thrombosis in cirrhosis. Am J Gastroenterol 2019; 114 (02) 258-266
- 11 Luca A, Caruso S, Milazzo M. et al. Natural course of extrahepatic nonmalignant partial portal vein thrombosis in patients with cirrhosis. Radiology 2012; 265 (01) 124-132
- 12 Maruyama H, Okugawa H, Takahashi M, Yokosuka O. De novo portal vein thrombosis in virus-related cirrhosis: predictive factors and long-term outcomes. Am J Gastroenterol 2013; 108 (04) 568-574
- 13 European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu. EASL clinical practice guidelines: vascular diseases of the liver. J Hepatol 2016; 64 (01) 179-202
- 14 Valeriani E, Riva N, Di Nisio M, Ageno W. Splanchnic vein thrombosis: current perspectives. Vasc Health Risk Manag 2019; 15: 449-461
- 15 Di Nisio M, Valeriani E, Riva N, Schulman S, Beyer-Westendorf J, Ageno W. Anticoagulant therapy for splanchnic vein thrombosis: ISTH SSC Subcommittee Control of Anticoagulation. J Thromb Haemost 2020; 18 (07) 1562-1568
- 16 Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6 (07) e1000097
-
17
Higgins JPT,
Altman DG,
Sterne JAC.
Assessing risk of bias in included studies. Cochrane Handbook Syst Rev Intervent Version 2019. Accessed at https://training.cochrane.org/cochrane-handbook-systematic-reviews-interventions
- 18 Sterne JA, Hernán MA, Reeves BC. et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ 2016; 355: i4919
- 19 Schulman S, Kearon C. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3 (04) 692-694
- 20 Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327 (7414): 557-560
- 21 Ageno W, Riva N, Schulman S. et al. Long-term clinical outcomes of splanchnic vein thrombosis: results of an international registry. JAMA Intern Med 2015; 175 (09) 1474-1480
- 22 Ageno W, Dentali F, Squizzato A. How I treat splanchnic vein thrombosis. Blood 2014; 124 (25) 3685-3691
- 23 R Core Team. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2019. Available at: https://www.R-project.org/2019
- 24 Garcia-Pagan JC, Valla DC. Portal vein thrombosis: a predictable milestone in cirrhosis?. J Hepatol 2009; 51 (04) 632-634
- 25 Stine JG, Shah PM, Cornella SL. et al. Portal vein thrombosis, mortality and hepatic decompensation in patients with cirrhosis: a meta-analysis. World J Hepatol 2015; 7 (27) 2774-2780
- 26 Yerdel MA, Gunson B, Mirza D. et al. Portal vein thrombosis in adults undergoing liver transplantation: risk factors, screening, management, and outcome. Transplantation 2000; 69 (09) 1873-1881
- 27 Bolognesi M, Di Pascoli M, Verardo A, Gatta A. Splanchnic vasodilation and hyperdynamic circulatory syndrome in cirrhosis. World J Gastroenterol 2014; 20 (10) 2555-2563
- 28 Senzolo M, Riva N, Dentali F. et al; IRSVT study investigators. Long-term outcome of splanchnic vein thrombosis in cirrhosis. Clin Transl Gastroenterol 2018; 9 (08) 176
- 29 Senzolo M, , M Sartori T, Rossetto V. et al. Prospective evaluation of anticoagulation and transjugular intrahepatic portosystemic shunt for the management of portal vein thrombosis in cirrhosis. Liver Int 2012; 32 (06) 919-927
- 30 Cui SB, Shu RH, Yan SP. et al. Efficacy and safety of anticoagulation therapy with different doses of enoxaparin for portal vein thrombosis in cirrhotic patients with hepatitis B. Eur J Gastroenterol Hepatol 2015; 27 (08) 914-919
- 31 Wang Z, Jiang MS, Zhang HL. et al. Is post-TIPS anticoagulation therapy necessary in patients with cirrhosis and portal vein thrombosis? A randomized controlled trial. Radiology 2016; 279 (03) 943-951
- 32 Hanafy AS, Abd-Elsalam S, Dawoud MM. Randomized controlled trial of rivaroxaban versus warfarin in the management of acute non-neoplastic portal vein thrombosis. Vascul Pharmacol 2019; 113: 86-91
- 33 Amitrano L, Guardascione MA, Scaglione M. et al. Splanchnic vein thrombosis and variceal rebleeding in patients with cirrhosis. Eur J Gastroenterol Hepatol 2012; 24 (12) 1381-1385
- 34 Artaza T, Lopes M, Romero M. et al. Efficacy and safety of anticoagulation in non-malignant portal vein thrombosis in patients with liver cirrhosis. Gastroenterol Hepatol 2018; 41 (10) 611-617
- 35 Cai M, Zhu K, Huang W. et al. Portal vein thrombosis after partial splenic embolization in liver cirrhosis: efficacy of anticoagulation and long-term follow-up. J Vasc Interv Radiol 2013; 24 (12) 1808-1816
- 36 Cerini F, Gonzalez JM, Torres F. et al. Impact of anticoagulation on upper-gastrointestinal bleeding in cirrhosis. A retrospective multicenter study. Hepatology 2015; 62 (02) 575-583
- 37 Chen H, Liu L, Qi X. et al. Efficacy and safety of anticoagulation in more advanced portal vein thrombosis in patients with liver cirrhosis. Eur J Gastroenterol Hepatol 2016; 28 (01) 82-89
- 38 Chung JW, Kim GH, Lee JH. et al. Safety, efficacy, and response predictors of anticoagulation for the treatment of nonmalignant portal-vein thrombosis in patients with cirrhosis: a propensity score matching analysis. Clin Mol Hepatol 2014; 20 (04) 384-391
- 39 De Gottardi A, Trebicka J, Klinger C. et al; VALDIG Investigators. Antithrombotic treatment with direct-acting oral anticoagulants in patients with splanchnic vein thrombosis and cirrhosis. Liver Int 2017; 37 (05) 694-699
- 40 Delgado MG, Seijo S, Yepes I. et al. Efficacy and safety of anticoagulation on patients with cirrhosis and portal vein thrombosis. Clin Gastroenterol Hepatol 2012; 10 (07) 776-783
- 41 Francoz C, Belghiti J, Vilgrain V. et al. Splanchnic vein thrombosis in candidates for liver transplantation: usefulness of screening and anticoagulation. Gut 2005; 54 (05) 691-697
- 42 Hernández Conde M, Llop Herrera E, de la Revilla Negro J. et al. Prevalence and outcome of portal thrombosis in a cohort of cirrhotic patients undergoing liver transplantation. Rev Esp Enferm Dig 2016; 108 (11) 716-720
- 43 Kwon J, Koh Y, Yu SJ, Yoon JH. Low-molecular-weight heparin treatment for portal vein thrombosis in liver cirrhosis: efficacy and the risk of hemorrhagic complications. Thromb Res 2018; 163: 71-76
- 44 La Mura V, Braham S, Tosetti G. et al. Harmful and beneficial effects of anticoagulants in patients with cirrhosis and portal vein thrombosis. Clin Gastroenterol Hepatol 2018; 16 (07) 1146-1152
- 45 Nagaoki Y, Aikata H, Daijyo K. et al. Efficacy and safety of edoxaban for treatment of portal vein thrombosis following danaparoid sodium in patients with liver cirrhosis. Hepatol Res 2018; 48 (01) 51-58
- 46 Riva N, Ageno W, Poli D. et al; Italian Federation of Anticoagulation Clinics (FCSA), Italian Federation of Anticoagulation Clinics FCSA. Safety of vitamin K antagonist treatment for splanchnic vein thrombosis: a multicenter cohort study. J Thromb Haemost 2015; 13 (06) 1019-1027
- 47 Rodriguez-Castro KI, Vitale A, Fadin M. et al. A prediction model for successful anticoagulation in cirrhotic portal vein thrombosis. Eur J Gastroenterol Hepatol 2019; 31 (01) 34-42
- 48 Sanchez-Ocaña R, Tejedor-Tejada J, Cimavilla-Roman M. et al. Utility of oral anticoagulants as prophylaxis of recurrent portal thrombosis after liver transplantation. Transplant Proc 2019; 51 (01) 83-86
- 49 Werner KT, Sando S, Carey EJ. et al. Portal vein thrombosis in patients with end stage liver disease awaiting liver transplantation: outcome of anticoagulation. Dig Dis Sci 2013; 58 (06) 1776-1780
- 50 Wu S, Wu Z, Zhang X, Wang R, Bai J. The incidence and risk factors of portal vein system thrombosis after splenectomy and pericardial devascularization. Turk J Gastroenterol 2015; 26 (05) 423-428
- 51 Wan YM, Li YH, Wu HM. et al. Portal vein thrombosis before and after transjugular intrahepatic portosystemic shunt placement: an observational study (STROBE compliant). Medicine (Baltimore) 2017; 96 (45) e8498
- 52 Yue-Meng W, Li YH, Wu HM, Yang J, Yang LH, Xu Y. Portal vein thrombosis in patients with cirrhosis undergoing elective transjugular intrahepatic portosystemic shunt: risk factors, warfarin efficacy, and clinical outcomes. Clin Appl Thromb Hemost 2018; 24 (03) 462-470