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      Anticoagulant therapy in patients with liver cirrhosis and portal vein thrombosis: insights for the clinician

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          Abstract

          Portal vein thrombosis (PVT) is a frequent complication in the natural history of patients with liver cirrhosis (LC). The prevalence of PVT in LC is highly variable, ranging from 0.6% to 25% according to different reports. The impact of PVT on the natural history of LC is unclear, but it seems to negatively affect the prognosis of patients undergoing liver transplantation (LT) by increasing post-LT mortality and delaying waiting time. The antithrombotic treatment of PVT is still challenging as PVT may often remain asymptomatic and incidentally diagnosed, and a spontaneous partial/total regression of PVT is observed in an important proportion of patients, even in the absence of anticoagulation. Recent evidence suggested that the anticoagulant treatment for PVT may favorably affect both ischemic and bleeding outcomes in LC patients. Anticoagulant therapies so far available include unfractioned heparin, low molecular weight heparins (LMWHs) and fondaparinux for acute treatment, and LMWHs and vitamin K antagonists (VKAs) for long-term treatment. No robust data currently support the use of direct oral anticoagulants (DOACs) in patients with LC and PVT, as the safety and efficacy of DOACs in this setting is still unclear. This review summarizes current evidence for the evaluation and management of patients with LC and PVT.

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          Most cited references49

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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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            Acute portal vein thrombosis unrelated to cirrhosis: a prospective multicenter follow-up study.

            Current recommendations for early anticoagulation in acute portal vein thrombosis unrelated to cirrhosis or malignancy are based on limited evidence. The aim of this study was to prospectively assess the risk factors, outcome, and prognosis in patients managed according to these recommendations. We enrolled 102 patients with acute thrombosis of the portal vein, or its left or right branch. Laboratory investigations for prothrombotic factors were centralized. Thrombus extension and recanalization were assessed by expert radiologists. A local risk factor was identified in 21% of patients, and one or several general prothrombotic conditions in 52%. Anticoagulation was given to 95 patients. After a median of 234 days, the portal vein and its left or right branch were patent in 39% of anticoagulated patients (versus 13% initially), the splenic vein in 80% (versus 57% initially), and the superior mesenteric vein in 73% (versus 42% initially). Failure to recanalize the portal vein was independently related to the presence of ascites (hazard ratio 3.8, 95% confidence interval 1.3-11.1) and an occluded splenic vein (hazard ratio 3.5, 95% confidence interval 1.4-8.9). Gastrointestinal bleeding and intestinal infarction occurred in nine and two patients, respectively. Two patients died from causes unrelated to thrombosis or anticoagulation therapy. Recanalization occurs in one-third of patients receiving early anticoagulation for acute portal vein thrombosis, whereas thrombus extension, intestinal infarction, severe bleeding, and death are rare. Alternative therapy should be considered when ascites and splenic vein obstruction are present.
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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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                Author and article information

                Contributors
                Journal
                Therap Adv Gastroenterol
                Therap Adv Gastroenterol
                TAG
                sptag
                Therapeutic Advances in Gastroenterology
                SAGE Publications (Sage UK: London, England )
                1756-283X
                1756-2848
                06 September 2018
                2018
                : 11
                : 1756284818793561
                Affiliations
                [1-1756284818793561]Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy
                [2-1756284818793561]Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy
                [3-1756284818793561]Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy
                [4-1756284818793561]I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, Rome, 00161, Italy
                Author notes
                [*]

                Stefania Basili and Daniele Pastori contributed equally to the manuscript.

                Article
                10.1177_1756284818793561
                10.1177/1756284818793561
                6128073
                04cef30a-e754-405f-a75a-8de792862887
                © The Author(s), 2018

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 5 May 2018
                : 28 June 2018
                Categories
                Review
                Custom metadata
                January-December 2018

                doacs,fondaparinux,liver cirrhosis,lmwh,portal vein thrombosis,vkas

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