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      Long-Term Outcome of Splanchnic Vein Thrombosis in Cirrhosis

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          Abstract

          Introduction

          Little is known about the long-term outcome of cirrhotic patients with splanchnic vein thrombosis (SVT). This prospective cohort study aimed to describe the clinical presentation, bleeding incidence, thrombotic events, and mortality in patients with SVT associated with cirrhosis.

          Methods

          Among 604 consecutive patients with SVT enrolled over 2 years, 149 had cirrhosis. Major bleeding, thrombotic events, and all-cause mortality were recorded during a 2-year follow-up. In a subgroup, the degree of recanalization with or without anticoagulation therapy, and the correlation between clinical events and liver disease severity were also investigated.

          Results

          The most common thrombosis sites were the portal (88%) and mesenteric veins (34%). At presentation, 50% of patients were asymptomatic. Anticoagulation was administered to 92/149 patients for a median of 6.5 months. Vessel recanalization was documented in 47/98 patients with a radiological follow-up. Anticoagulation was associated with a 3.33-fold higher of recanalization rate, and a lower recurrent thrombosis rate, while patients with and without anticoagulation experienced a similar rate of major bleeding episodes. Mortality rates were 6.8 per 100 patient-years for patients with thrombosis completely or partially resolving during the follow-up, and 15.4 per 100 patient-years for those with stable or progressing thrombosis. An impact of SVT on survival was only apparent in patients with more advanced liver disease (Child–Pugh B-C).

          Conclusions

          Patients with SVT and cirrhosis have a substantial long-term risk of recurrent thrombotic events, which is reduced by anticoagulation therapy without any increase in bleeding risk. Anticoagulation can improve the likelihood of vessel recanalization, and is associated with a lower risk of death for decompensated patients.

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          Most cited references24

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          Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis.

          We performed a randomized controlled trial to evaluate the safety and efficacy of enoxaparin, a low-molecular-weight heparin, in preventing portal vein thrombosis (PVT) in patients with advanced cirrhosis. In a nonblinded, single-center study, 70 outpatients with cirrhosis (Child-Pugh classes B7-C10) with demonstrated patent portal veins and without hepatocellular carcinoma were assigned randomly to groups that were given enoxaparin (4000 IU/day, subcutaneously for 48 weeks; n = 34) or no treatment (controls, n = 36). Ultrasonography (every 3 months) and computed tomography (every 6 months) were performed to check the portal vein axis. The primary outcome was prevention of PVT. Radiologists and hepatologists that assessed outcomes were blinded to group assignments. Analysis was by intention to treat. At 48 weeks, none of the patients in the enoxaparin group had developed PVT, compared with 6 of 36 (16.6%) controls (P = .025). At 96 weeks, no patient developed PVT in the enoxaparin group, compared with 10 of 36 (27.7%) controls (P = .001). At the end of the follow-up period, 8.8% of patients in the enoxaparin group and 27.7% of controls developed PVT (P = .048). The actuarial probability of PVT was lower in the enoxaparin group (P = .006). Liver decompensation was less frequent among patients given enoxaparin (11.7%) than controls (59.4%) (P < .0001); overall values were 38.2% vs 83.0%, respectively (P < .0001). The actuarial probability of liver decompensation was lower in the enoxaparin group (P < .0001). Eight patients in the enoxaparin group and 13 controls died. The actuarial probability of survival was higher in the enoxaparin group (P = .020). No relevant side effects or hemorrhagic events were reported. In a small randomized controlled trial, a 12-month course of enoxaparin was safe and effective in preventing PVT in patients with cirrhosis and a Child-Pugh score of 7-10. Enoxaparin appeared to delay the occurrence of hepatic decompensation and to improve survival. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.
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            Effects of Anticoagulants in Patients With Cirrhosis and Portal Vein Thrombosis: a Systematic Review and Meta-Analysis.

            Liver cirrhosis is complicated by bleeding from portal hypertension but also by portal vein thrombosis (PVT). PVT occurs in about 20%-50% of patients with cirrhosis, and is a warning sign for poor outcome. It is a challenge to treat patients with cirrhosis using anticoagulants, because of the perception that the coexistent coagulopathy could promote bleeding. We performed a systematic review and meta-analysis to determine the effects of anticoagulant therapy in patients with cirrhosis and PVT.
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              Causes and consequences of portal vein thrombosis in 1,243 patients with cirrhosis: results of a longitudinal study.

              In cirrhosis, portal vein thrombosis (PVT) could be a cause or a consequence of the progression of liver disease. We analyzed data from a prospective trial of ultrasound screening for hepatocellular carcinoma in order to identify risk factors for and the impact of PVT in patients with cirrhosis. In all, 1,243 adults with cirrhosis without PVT were enrolled from 43 liver units in France and Belgium between June 2000 and March 2006. The mean follow-up was 47 months. Doppler ultrasonography was used to check the portal vein. Progression of liver disease was defined by the development of: ascites, hepatic encephalopathy, variceal bleeding, prothrombin 45 μmol/L, albumin 115 μmol/L. G20210A prothrombin and factor V gene mutations were assessed in sera stored at three large centers. The 5-year cumulative incidence of PVT was 10.7%. PVT was mostly partial and varied over time. The development of PVT was independently associated with baseline esophageal varices (P = 0.01) and prothrombin time (P = 0.002), but not with disease progression before PVT, or prothrombotic mutations. Disease progression was independently associated with baseline age (hazard ratio [HR] 1.55; 95% confidence interval [CI]: 1.11-2.17), body mass index (HR 1.40; 95% CI: 1.01-1.95), prothrombin time (HR 0.79; 95% CI: 0.70-0.90), serum albumin (HR 0.97; 95% CI: 0.94-0.99), and esophageal varices (HR 1.70; 95% CI: 1.21-2.38) but not with the prior development of PVT (HR 1.32; 95% CI: 0.68-2.65). In patients with cirrhosis, the development of PVT is associated with the severity of liver disease at baseline, but does not follow a recent progression of liver disease. There is no evidence that the development of PVT is responsible for further progression of liver disease. © 2014 by the American Association for the Study of Liver Diseases.
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                Author and article information

                Contributors
                +0039.049.8218726 , marcosenzolo@hotmail.com
                Journal
                Clin Transl Gastroenterol
                Clin Transl Gastroenterol
                Clinical and Translational Gastroenterology
                Nature Publishing Group US (New York )
                2155-384X
                15 August 2018
                August 2018
                : 9
                : 8
                : 176
                Affiliations
                [1 ]ISNI 0000 0004 1760 2630, GRID grid.411474.3, Multivisceral Transplant Unit, , University Hospital of Padua, ; Padua, Italy
                [2 ]ISNI 0000000121724807, GRID grid.18147.3b, Department of Clinical and Experimental Medicine, , University of Insubria, ; Varese, Italy
                [3 ]ISNI 0000 0004 1760 2630, GRID grid.411474.3, Clinical Medicine I, Department of Medicine, , Padua University Hospital, ; Padua, Italy
                [4 ]ISNI 0000 0004 0647 3378, GRID grid.412480.b, Department of Internal Medicine, , Seoul National University Bundang Hospital, ; Seongnam, Republic of Korea
                [5 ]ISNI 0000 0004 1757 8749, GRID grid.414818.0, A. Bianchi Bonomi Hemophilia and Thrombosis Center, , Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, ; Milan, Italy
                [6 ]ISNI 0000 0004 1936 8227, GRID grid.25073.33, Department of Medicine, , McMaster University, ; Hamilton, Canada
                [7 ]GRID grid.419450.d, Hemostasis and Thrombosis Center, , A.O. Istituti Ospitalieri di Cremona, ; Cremona, Italy
                [8 ]ISNI 0000 0001 2111 7257, GRID grid.4488.0, Thrombosis Research, Department of Medicine, 1st Division of Hematology, , Dresden University Clinic, ; Dresden, Germany
                [9 ]ISNI 0000 0001 0790 385X, GRID grid.4691.a, Department of Advanced Biomedical Sciences, Division of Cardiology, , Federico II University, ; Naples, Italy
                Article
                43
                10.1038/s41424-018-0043-2
                6092393
                30108204
                ac289b4f-4f8e-408d-8965-45c0a29ef600
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 30 April 2018
                : 7 June 2018
                : 16 June 2018
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                © The Author(s) 2018

                Gastroenterology & Hepatology
                Gastroenterology & Hepatology

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