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      Therapy Algorithm for Portal Vein Thrombosis in Liver Cirrhosis: The Internist's Point of View

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          Abstract

          Background

          Treatment of non-malignant portal vein thrombosis (PVT) in patients with cirrhosis has been neglected in the past because of the fear of bleeding complications when using anticoagulation and due to the technical difficulties associated with the implantation of the transjugular intrahepatic portosystemic shunt (TIPS). However, PVT has a negative impact on outcome and compromises liver transplantation, warranting treatment by using anticoagulation and TIPS.

          Methods

          This review considers studies on the treatment of PVT in cirrhosis published in the last 10 years. Unfortunately, many of these studies are limited by their retrospective design and a small sample size.

          Results

          Anticoagulation using low-molecular-weight heparin (LMWH) or vitamin K antagonists is effective in the treatment of patients with limited and recent PVT, resulting in a recanalization in up to 50% of the patients. TIPS (plus local measures) results in a recanalization of up to 100% and reduces the rebleeding rate considerably in patients with recent or chronic PVT.

          Conclusion

          Based on the presently limited knowledge, a therapy algorithm is suggested favouring the TIPS as a first-line treatment for PVT in patients with symptomatic portal hypertension. Patients with thus far asymptomatic portal hypertension may first receive anticoagulation, preferably using LMWH. If these patients have a condition where anticoagulation is not promising (complete, extended, chronic PVT) or ineffective, or if they are candidates for liver transplantation, the TIPS may be implanted without delay.

          Zusammenfassung

          Hintergrund

          Die nichtmaligne Pfortaderthrombose (PVT) beim Zirrhosepatienten galt bis vor wenigen Jahren als schicksalhafte Komplikation, deren spezifische Behandlung mittels Antikoagulation aus Sorge vor Blutungskomplikationen nicht durchgeführt wurde. Auch die Implantation eines transjugulären intrahepatischen portosystemischen Shunt (TIPS) galt lange Zeit aus technischen Gründen als kontraindiziert. Die Probleme, die durch den Pfortaderverschluss im Rahmen der Lebertransplantation auftraten, zwangen zum Umdenken und bewirkten die ersten Therapieversuche sowohl mit Antikoagulanzien als auch mit TIPS.

          Methoden

          Diese Übersichtsarbeit wertet Studien aus, die in den letzten 10 Jahren zu diesem Thema publiziert wurden. Bei den meisten Studien handelt es sich jedoch um retrospektive Auswertungen mit einer geringen Patientenzahl. Dies schränkt die Qualität der hieraus gewonnenen Empfehlung ein.

          Ergebnisse

          Die Antikoagulation mit niedermolekularem Heparin oder Vitamin-K-Antagonisten ist effektiv und resultiert in einer Rekanalisation bei bis zu 50% der Patienten. Die Effektivität ist abhängig vom Grad der Thrombose (partiell oder komplett), von ihrer Ausdehnung (begrenzt oder in die zuführenden Venen reichend) und von deren Alter (frisch oder chronisch). Die Anlage eines TIPS (eventuell zusammen mit lokalen Maßnahmen) kann in bis zu 100% zu einer Rekanalisation des Portalsystems führen. Bei chronischer oder kavernomatöser PVT kann ebenfalls eine TIPS-Anlage sinnvoll sein, da sie die Blutungsrate signifikant reduziert.

          Schlussfolgerung

          Auf der Grundlage der begrenzten Datenlage wird ein Therapiealgorithmus vorgestellt. Bei Patienten mit symptomatischer portaler Hypertension (insbesondere Varizenblutungen und Aszites) erscheint die frühe TIPS-Anlage empfehlenswert, da sie nicht nur die PVT, sondern auch die Symptome der portalen Hypertension bessert und zu einer Lebensverlängerung beitragen kann. Asymptomatische Patienten können mit einer Antikoagulation behandelt werden, wenn diese Erfolg versprechend erscheint (inkomplette und/oder begrenzte Thrombose, keine chronische PVT). Bei kompletter, ausgedehnter oder chronischer PVT, ungenügendem Ansprechen auf eine vorausgegangene Antikoagulation oder bevorstehender Lebertransplantation ist auch bei asymptomatischen Patienten an die Anlage eines dünnlumigen TIPS zu denken.

          Related collections

          Most cited references 40

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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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            Splanchnic vein thrombosis in candidates for liver transplantation: usefulness of screening and anticoagulation.

            Splanchnic vein thrombosis is a significant source of complications in candidates for liver transplantation. The aims of this study were: (a) to determine the prevalence of and risk factors for splanchnic vein thrombosis in cirrhotic patients awaiting transplantation and (b) to assess the usefulness of anticoagulation. A total of 251 cirrhotic patients listed for transplantation were analysed. All underwent systematic screening for thrombosis with Doppler ultrasonography. During the second period of the study, all patients with thrombosis received anticoagulation up to transplantation while during the first period none had received anticoagulation. The incidence of splanchnic vein thrombosis at evaluation was 8.4%. Seventeen additional patients (7.4%) developed de novo thrombosis after evaluation. Independent risk factors for thrombosis were low platelet count (77.4 (36.3) v 111.6 (69.2) 10(9)/l; p = 0.001), a past history of variceal bleeding (47.4% v 29.1%; p = 0.003), and a prolonged interval from listing to transplantation (8.5 (6.8) v 4.8 (4.4) months; p = 0.002). The proportion of partial or complete recanalisation was significantly higher in those who received (8/19) than in those who did not receive (0/10, p = 0.002) anticoagulation. Survival was significantly lower in those who had complete portal vein thrombosis at the time of surgery (p = 0.04). These results support a systematic screening for splanchnic vein thrombosis in patients awaiting transplantation. They suggest that in these patients, anticoagulation is safe and has a significant impact on recanalisation as well as prevention of extension of thrombosis.
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              Risk factors and clinical presentation of portal vein thrombosis in patients with liver cirrhosis.

              Portal vein thrombosis in patients with liver cirrhosis is usually associated to hepatocellular carcinoma. Clinical presentation of non-neoplastic portal vein thrombosis (PVT) in cirrhotic patients has not been specifically studied and risk factors of PVT in this group of patients are still poorly understood. We studied all patients with PVT and liver cirrhosis admitted to our Unit from January 1998 to December 2002. They were paired (by gender, age and Child-Pugh score) to a group of cirrhotic patients without PVT and screened for acquired and inherited thrombophilic risk factors. These factors together with the site of thrombosis and the severity of the liver disease were correlated to the clinical presentation of PVT. Out of a total of 701 cirrhotic patients admitted to our hospital and routinely screened with Doppler ultrasound, 79 (11.2%) were found to have PVT. Of these, 34 (43%) were asymptomatic and 45 (57%) were symptomatic (31 presented with portal hypertensive bleed and 14 with abdominal pain, 10 of whom had intestinal infarction). Mesenteric vein involvement was never asymptomatic and lead to intestinal ischemia or infarction. Most patients were in class Child-Pugh B and C. Among thrombophilic risk factors studied only the mutation 20210 of the prothrombin gene resulted independently associated to PVT. Portal vein thrombosis may be completely asymptomatic in patients with liver cirrhosis; however in more than half of cases presents with life-threatening complications such as gastrointestinal haemorrhage and intestinal infarction. Cirrhotic patients with PVT usually have an advanced liver disease and the presence of the mutation 20210 of the prothrombin gene increases more than fivefold the risk of PVT.
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                Author and article information

                Journal
                Viszeralmedizin
                Viszeralmedizin
                VIM
                Viszeralmedizin
                S. Karger Verlag für Medizin und Naturwissenschaften GmbH (Wilhelmstrasse 20A, P.O. Box · Postfach · Case postale, D–79095, Freiburg, Germany · Deutschland · Allemagne, Phone: +49 761 45 20 70, Fax: +49 761 4 52 07 14, information@karger.de )
                1662-6664
                1662-6672
                December 2014
                4 December 2014
                1 December 2015
                : 30
                : 6
                : 401-408
                Affiliations
                a‘PraxisZentrum für Gastroenterologie und Endokrinologie’ and University Hospital Freiburg, Freiburg i.Br., Germany
                bDepartment of Gastroenterology, Hepatology, Endocrinology and Infectious Diseases, University Hospital Freiburg, Freiburg i.Br., Germany
                cDepartment of Gastroenterology, Klinikum Ludwigsburg, Ludwigsburg, Germany
                Author notes
                *Prof. Dr. Martin Rössle, PraxisZentrum für Gastroenterologie und Endokrinologie, Bertoldstraße 48, 79098 Freiburg, Germany, Martin-Roessle@ 123456t-online.de
                Article
                vim-0030-0401
                10.1159/000370053
                4513837
                26288607
                Copyright © 2014 by S. Karger GmbH, Freiburg
                Page count
                Figures: 8, Tables: 3, References: 44, Pages: 8
                Categories
                Review Article • Übersichtsarbeit

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