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1
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Ayoub M, Faris C, Chumbe JT, Daglilar E, Anwar N, Naravadi V. Safety of DOACs in patients with Child-Pugh Class C cirrhosis and atrial fibrillation. JGH Open 2024; 8:e13074. [PMID: 38699468 PMCID: PMC11063728 DOI: 10.1002/jgh3.13074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 03/20/2024] [Accepted: 04/12/2024] [Indexed: 05/05/2024]
Abstract
Background Anticoagulation (AC) is used for stroke prevention in atrial fibrillation (AF). Direct Oral Anticoagulants (DOACs) are safe in patients with AF without cirrhosis, they are hardly studied in patients with advanced cirrhosis. Our study evaluates the safety and outcomes of DOACs in patients with Child-Pugh class C cirrhosis (CPC). Methods We queried TriNetX Database. Patients with CPC and AF were divided into three cohorts: patients on DOACs, no AC, and warfarin. Three study arms were created using a 1:1 propensity score matching system (PSM). Results Totally 16 029 patients met the inclusion criteria. Of those, 20.2% (n = 3235) were on DOACs, 47.1% (n = 7552) were not on AC, and 32.7% (n = 5242) were on warfarin. First arm comparing AC versus no AC, a statistically significant benefit was identified in 3-year mortality risk (47% vs 71%, P < 0.0001) and transplant status (17% vs 5%, p < 0.0001) with AC. However, no significant difference was identified regarding intracranial hemorrhage and GI bleeding risk. Second arm comparing patients on DOACs versus no AC, we identified mortality benefit (40% vs 72%, P < 0.0001) and a higher transplant rate (9% vs 3.2%, P < 0.0001) with DOACs. Intracranial hemorrhage rates (6% vs 4%, P = 0.03) were higher in patients on DOACs. Third arm comparing patients on DOACs versus Warfarin, a statistically significant lower risk of intracranial hemorrhage (6.6% vs 8.7%, P = 0.004) and GI bleed (2% vs 2.4%, P < 0.0001) were identified in patients on DOACs. Conclusion Anticoagulation is safe in patients with CPC with AF and may provide a mortality benefit. DOACs are a safer alternative to warfarin.
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Affiliation(s)
- Mark Ayoub
- West Virginia University Charleston Division, Internal Medicine DepartmentCharleston Area Medical CenterCharlestonWest VirginiaUSA
| | - Carol Faris
- Marshall University School of MedicineSurgery DepartmentHuntingtonWest VirginiaUSA
| | - Julton Tomanguillo Chumbe
- West Virginia University Charleston Division, Internal Medicine DepartmentCharleston Area Medical CenterCharlestonWest VirginiaUSA
| | - Ebubekir Daglilar
- Department of Gastroenterology, Charleston DivisionWest Virginia University School of Medicine, Charleston Area Medical CenterCharlestonWest VirginiaUSA
| | - Nadeem Anwar
- Department of Gastroenterology, Charleston DivisionWest Virginia University School of Medicine, Charleston Area Medical CenterCharlestonWest VirginiaUSA
| | - Vishnu Naravadi
- Department of Gastroenterology, Charleston DivisionWest Virginia University School of Medicine, Charleston Area Medical CenterCharlestonWest VirginiaUSA
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2
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Elshafey SA, Brown RS. Nonviral or Drug-Induced Etiologies of Acute-on-Chronic Liver Failure (Autoimmune, Vascular, and Malignant). Clin Liver Dis 2023; 27:649-657. [PMID: 37380288 DOI: 10.1016/j.cld.2023.03.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/30/2023]
Abstract
Vascular, autoimmune hepatitis, and malignant causes of acute-on-chronic liver failure are rare but important to consider and investigate in patients with underlying liver disease who present with acute deterioration and other more common etiologies have been excluded. Vascular processes including Budd-Chiari syndrome and portal vein thrombosis require imaging for diagnosis and anticoagulation is the mainstay of therapy. Patients may require advanced interventional therapy including transjugular intrahepatic portosystemic shunt or consideration of liver transplantation. Autoimmune hepatitis is a complex disease entity that requires a high degree of clinical suspicion and can present heterogeneously.
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Affiliation(s)
- Suzanne A Elshafey
- Division of Gastroenterology and Hepatology, Weill Cornell Medicine, 1305 York Avenue, 4th Floor, New York, NY 10021, USA
| | - Robert S Brown
- Division of Gastroenterology and Hepatology, Weill Cornell Medicine, 1305 York Avenue, 4th Floor, New York, NY 10021, USA.
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3
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Gîrleanu I, Trifan A, Huiban L, Muzica CM, Petrea OC, Sîngeap AM, Cojocariu C, Chiriac S, Cuciureanu T, Stafie R, Zenovia S, Stratina E, Rotaru A, Nastasa R, Sfarti C, Costache II, Stanciu C. Anticoagulation for Atrial Fibrillation in Patients with Decompensated Liver Cirrhosis: Bold and Brave? Diagnostics (Basel) 2023; 13:1160. [PMID: 36980468 PMCID: PMC10047341 DOI: 10.3390/diagnostics13061160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Revised: 03/07/2023] [Accepted: 03/15/2023] [Indexed: 03/30/2023] Open
Abstract
Atrial fibrillation is frequently diagnosed in patients with liver cirrhosis, especially in those with non-alcoholic steatohepatitis or alcoholic etiology. Anticoagulant treatment is recommended for thromboembolic protection in patients with atrial fibrillation. Considering the impaired coagulation balance in liver cirrhosis, predisposing patients to bleed or thrombotic events, the anticoagulant treatment is still a matter of debate. Although patients with liver cirrhosis were excluded from the pivotal studies that confirmed the efficacy and safety of the anticoagulant treatment in patients with atrial fibrillation, data from real-life cohorts demonstrated that the anticoagulant treatment in patients with liver cirrhosis could be safe. This review aimed to evaluate the recent data regarding the safety and efficacy of anticoagulant treatment in patients with decompensated liver cirrhosis. Direct oral anticoagulants are safer than warfarin in patients with compensated liver cirrhosis. In Child-Pugh class C liver cirrhosis, direct oral anticoagulants are contraindicated. New bleeding and ischemic risk scores should be developed especially for patients with liver cirrhosis, and biomarkers for bleeding complications should be implemented in clinical practice to personalize this treatment in a very difficult population represented by decompensated liver cirrhosis patients.
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Affiliation(s)
- Irina Gîrleanu
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Anca Trifan
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Laura Huiban
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Cristina Maria Muzica
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Oana Cristina Petrea
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Ana-Maria Sîngeap
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Camelia Cojocariu
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Stefan Chiriac
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Tudor Cuciureanu
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Remus Stafie
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Sebastian Zenovia
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Ermina Stratina
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Adrian Rotaru
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Robert Nastasa
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Catalin Sfarti
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Irina Iuliana Costache
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Cardiology Department, “Saint Spiridon” University Hospital, 700115 Iasi, Romania
| | - Carol Stanciu
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
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4
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Semmler G, Pomej K, Bauer DJM, Balcar L, Simbrunner B, Binter T, Hartl L, Becker J, Pinter M, Quehenberger P, Trauner M, Mandorfer M, Lisman T, Reiberger T, Scheiner B. Safety of direct oral anticoagulants in patients with advanced liver disease. Liver Int 2021; 41:2159-2170. [PMID: 34152697 PMCID: PMC8456813 DOI: 10.1111/liv.14992] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 05/28/2021] [Accepted: 06/18/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS While direct oral anticoagulants (DOACs) are increasingly used in patients with liver disease, safety data especially in advanced chronic liver disease (ACLD) are limited. METHODS Liver disease patients receiving DOAC treatment (ACLD: n = 104; vascular liver disease: n = 29) or vitamin K antagonists (VKA)/low-molecular-weight heparin (LMWH; ACLD: n = 45; vascular: n = 13) between January 2010 and September 2020 were retrospectively included. Invasive procedures and bleeding events were recorded. Calibrated anti-Xa peak levels and thrombomodulin-modified thrombin generation assays (TM-TGAs) were measured in a subgroup of 35/28 DOAC patients. RESULTS Among patients receiving DOAC, 55 (41.3%) had advanced liver dysfunction (Child-Pugh-stage [CPS] B/C) and 66 (49.6%) had experienced decompensation. Overall, 205 procedures were performed in 60 patients and procedure-related bleedings occurred in 7 (11.7%) patients. Additionally, 38 (28.6%) patients experienced spontaneous (15 minor, 23 major) bleedings during a median follow-up of 10.5 (IQR: 4.0-27.8) months. Spontaneous bleedings in ACLD patients were more common in CPS-B/C (at 12 months: 36.9% vs CPS-A: 15.9%, subdistribution hazard ratio [SHR]: 3.23 [95% CI: 1.59-6.58], P < .001), as were major bleedings (at 12 months: 22.0% vs 5.0%, SHR: 5.82 [95% CI: 2.00-16.90], P < .001). Importantly, CPS (adjusted SHR: 4.12 [91% CI: 1.82-9.37], P < .001), but not the presence of hepatocellular carcinoma or varices, was independently associated with major bleeding during DOAC treatment. Additionally, ACLD patients experiencing bleeding had worse overall survival (at 12 months: 88.9% vs 95.0% without bleeding; P < .001). Edoxaban anti-Xa peak levels were higher in patients with CPS-B/C (345 [95% CI: 169-395] vs CPS-A: 137 [95% CI: 96-248] ng/mL, P = .048) and were associated with lower TM-TGA. Importantly, spontaneous bleeding rates were comparable to VKA/LMWH patients. CONCLUSIONS Anticoagulants including DOACs should be used with caution in patients with advanced liver disease due to a significant rate of spontaneous bleeding events.
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Affiliation(s)
- Georg Semmler
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria
| | - Katharina Pomej
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria
| | - David J. M. Bauer
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria
| | - Lorenz Balcar
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria
| | - Benedikt Simbrunner
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria,Christian Doppler Laboratory for Portal Hypertension and Liver FibrosisMedical University of ViennaViennaAustria
| | - Teresa Binter
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria
| | - Lukas Hartl
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria
| | - Jeannette Becker
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria
| | - Matthias Pinter
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria
| | - Peter Quehenberger
- Department of Laboratory MedicineMedical University of ViennaViennaAustria
| | - Michael Trauner
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Mattias Mandorfer
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria
| | - Ton Lisman
- Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver TransplantationDepartment of SurgeryUniversity of Groningen, University Medical Center GroningenGroningenthe Netherlands
| | - Thomas Reiberger
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria,Christian Doppler Laboratory for Portal Hypertension and Liver FibrosisMedical University of ViennaViennaAustria
| | - Bernhard Scheiner
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria
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5
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Abstract
Portal vein thrombosis (PVT) is a splanchnic vascular disorder characterised by a recent or chronic thrombotic occlusion of the portal venous system. Its aetiology is miscellaneous, and its management is demanding since PVT can play a critical role as far as morbidity and mortality are concerned. Indeed, PVT can develop as a complication of portal hypertension (PH), in association or not with advanced chronic liver disease, and aggravate its clinical consequences such as variceal bleeding and ascites. Furthermore, a diagnosis of PVT in a non-cirrhotic context can potentially reveal a previously unknown hypercoagulable condition, requiring further diagnostic steps and specific treatment in addition to anticoagulation. In addition to established therapeutic approaches, new strategies, including newer pharmacological treatments and interdisciplinary invasive procedures, gain more attention and have been increasingly introduced into clinical practice. This review aims at discussing the current knowledge in terms of treatment options for PVT.
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6
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Safety of direct oral anticoagulants in patients with mild to moderate cirrhosis: a systematic review and meta-analysis. J Thromb Thrombolysis 2021; 52:817-827. [PMID: 33728575 DOI: 10.1007/s11239-021-02424-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/01/2021] [Indexed: 12/21/2022]
Abstract
To evaluate major bleeding in cirrhosis with use of traditional anticoagulation or direct oral anticoagulants (DOACs), using a standardized definition. Anticoagulation in patients with cirrhosis is often a clinical conundrum for providers as the necessary balance between thrombotic and bleeding risk is complicated by end organ damage. Recent meta-analyses have sought to evaluate the safety and efficacy of direct oral anticoagulants in patients with liver disease. These recent analyses are limited by various bleeding definitions, broad inclusion criteria, and few indications for anticoagulation. We sought to conduct a meta-analysis using a validated definition for major bleeding and compare rates between traditional anticoagulation and DOACs in patients with cirrhosis. Articles were eligible for inclusion if the international society on thrombosis and hemostasis (ISTH) definition of a major bleed was the primary safety outcome. Additionally, only articles including patients with cirrhosis and receiving treatment with anticoagulation for an indication for stroke prevention or venous thromboembolism were eligible. Eligible articles needed a DOAC comparator group against traditional anticoagulant medication. Seven studies met inclusion criteria and compiled data for 683 patients in the meta-analysis. Pooled trial analysis demonstrated no statistically significant difference in the primary outcome of ISTH major bleeding (OR 0.55, 95%CI 0.28-1.07, I2 0%). Individual secondary outcomes of all bleeding, intracerebral hemorrhage, or gastrointestinal bleeding also demonstrated no significant difference between DOACs and traditional anticoagulation. Use of DOACs in patients with mild to moderate cirrhosis carries similar risk to use of traditional anticoagulation.
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7
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Northup PG, Garcia-Pagan JC, Garcia-Tsao G, Intagliata NM, Superina RA, Roberts LN, Lisman T, Valla DC. Vascular Liver Disorders, Portal Vein Thrombosis, and Procedural Bleeding in Patients With Liver Disease: 2020 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2021; 73:366-413. [PMID: 33219529 DOI: 10.1002/hep.31646] [Citation(s) in RCA: 369] [Impact Index Per Article: 92.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Accepted: 11/16/2020] [Indexed: 12/12/2022]
Affiliation(s)
- Patrick G Northup
- Division of Gastroenterology and Hepatology, Center for the Study of Hemostasis in Liver Disease, University of Virginia, Charlottesville, VA
| | - Juan Carlos Garcia-Pagan
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi I i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.,Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE-Liver), Barcelona, Spain
| | - Guadalupe Garcia-Tsao
- Department of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, CT.,Veterans Administration Healthcare System, West Haven, CT
| | - Nicolas M Intagliata
- Division of Gastroenterology and Hepatology, Center for the Study of Hemostasis in Liver Disease, University of Virginia, Charlottesville, VA
| | - Riccardo A Superina
- Department of Transplant Surgery, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL
| | - Lara N Roberts
- Department of Haematological Medicine, King's Thrombosis Centre, King's College Hospital National Health Service (NHS) Foundation Trust, London, United Kingdom
| | - Ton Lisman
- Section of Hepatobiliary Surgery and Liver Transplantation, Surgical Research Laboratory, Department of Surgery, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
| | - Dominique C Valla
- Hepatology Service, Hospital Beaujon, Clichy, France.,Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE-Liver), Barcelona, Spain
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8
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Yen HW. Fatal Nonvariceal Gastrointestinal Bleeding in a Cirrhotic Patient Taking Apixaban with No History of Hemorrhage. Cureus 2019; 11:e6126. [PMID: 31886064 PMCID: PMC6903885 DOI: 10.7759/cureus.6126] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
This report describes a cirrhotic female patient with no history of bleeding or other gastrointestinal disorder who experienced fatal gastrointestinal bleeding (GIB) after taking apixaban [which is a direct oral anticoagulant (DOAC)] for one month for management of chronic nonvalvular atrial fibrillation. The use of apixaban, coupled with the predilection for hemorrhage in cirrhotic patients, most likely contributed to her fatal GIB. Caution should be exercised in considering apixaban and potentially other members of the DOAC class for the treatment of cirrhotic patients until further research can explore the safety of DOAC therapy in cirrhotic patients.
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Affiliation(s)
- Hung-Wen Yen
- Internal Medicine, Louise A. Weiss Memorial Hospital, Chicago, USA
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9
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Sanchez-Redondo J, Espinosa G, Varillas Delgado D, Cervera R. Recurrent Thrombosis With Direct Oral Anticoagulants in Antiphospholipid Syndrome: A Systematic Literature Review and Meta-analysis. Clin Ther 2019; 41:1839-1862. [PMID: 31405527 DOI: 10.1016/j.clinthera.2019.06.015] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Revised: 06/04/2019] [Accepted: 06/25/2019] [Indexed: 01/30/2023]
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10
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Faccia M, Ainora ME, Ponziani FR, Riccardi L, Garcovich M, Gasbarrini A, Pompili M, Zocco MA. Portal vein thrombosis in cirrhosis: Why a well-known complication is still matter of debate. World J Gastroenterol 2019; 25:4437-4451. [PMID: 31496623 PMCID: PMC6710174 DOI: 10.3748/wjg.v25.i31.4437] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2019] [Revised: 07/08/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Portal vein thrombosis (PVT) represents a well-known complication during the natural course of liver cirrhosis (LC), ranging from asymptomatic cases to life-threating conditions related to portal hypertension and hepatic decompensation. Portal flow stasis, complex acquired hypercoagulable disorders and exogenous factors leading to endothelial dysfunction have emerged as key factors for PVT development. However, PVT occurrence remains unpredictable and many issues regarding its natural history, prognostic significance and treatment are still elusive. In particular although spontaneous resolution or disease stability occur in most cases of PVT, factors predisposing to disease progression or recurrence after spontaneous recanalization are not clarified as yet. Moreover, PVT impact on LC outcome is still debated, as PVT may represent itself a consequence of liver fibrosis and hepatic dysfunction progression. Anticoagulation and transjugular intrahepatic portosystemic shunt are considered safe and effective in this setting and are recommended in selected cases, even if the safer therapeutic option and the optimal therapy duration are still unknown. Nevertheless, their impact on mortality rates should be addressed more extensively. In this review we present the most debated questions regarding PVT, whose answers should come from prospective cohort studies and large sample-size randomized trials.
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Affiliation(s)
- Mariella Faccia
- Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University, Rome 00168, Italy
| | - Maria Elena Ainora
- Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University, Rome 00168, Italy
| | - Francesca Romana Ponziani
- Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University, Rome 00168, Italy
| | - Laura Riccardi
- Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University, Rome 00168, Italy
| | - Matteo Garcovich
- Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University, Rome 00168, Italy
| | - Antonio Gasbarrini
- Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University, Rome 00168, Italy
| | - Maurizio Pompili
- Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University, Rome 00168, Italy
| | - Maria Assunta Zocco
- Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University, Rome 00168, Italy
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11
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Hernández-Gea V, De Gottardi A, Leebeek FWG, Rautou PE, Salem R, Garcia-Pagan JC. Current knowledge in pathophysiology and management of Budd-Chiari syndrome and non-cirrhotic non-tumoral splanchnic vein thrombosis. J Hepatol 2019; 71:175-199. [PMID: 30822449 DOI: 10.1016/j.jhep.2019.02.015] [Citation(s) in RCA: 72] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Revised: 02/15/2019] [Accepted: 02/19/2019] [Indexed: 12/11/2022]
Abstract
Budd-Chiari syndrome and non-cirrhotic non-tumoral portal vein thrombosis are 2 rare disorders, with several similarities that are categorized under the term splanchnic vein thrombosis. Both disorders are frequently associated with an underlying prothrombotic disorder. They can cause severe portal hypertension and usually affect young patients, negatively influencing life expectancy when the diagnosis and treatment are not performed at an early stage. Yet, they have specific features that require individual consideration. The current review will focus on the available knowledge on pathophysiology, diagnosis and management of both entities.
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Affiliation(s)
- Virginia Hernández-Gea
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, European Reference Network for Rare Vascular Liver Diseases, Universitat de Barcelona, Spain
| | - Andrea De Gottardi
- Hepatology, University Clinic of Visceral Medicine and Surgery, Inselspital, and Department of Biomedical Research, University of Bern, Bern, Switzerland
| | - Frank W G Leebeek
- Department of Haematology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Pierre-Emmanuel Rautou
- Service d'Hépatologie, Centre de Référence des Maladies Vasculaires du Foie, DHU Unity, Pôle des Maladies de l'Appareil Digestif, Hôpital Beaujon, AP-HP, Clichy, France; Inserm, UMR-970, Paris Cardiovascular Research Center, PARCC, Paris, France
| | - Riad Salem
- Department of Radiology, Section of Interventional Radiology, Northwestern University, Chicago, IL, USA
| | - Juan Carlos Garcia-Pagan
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, European Reference Network for Rare Vascular Liver Diseases, Universitat de Barcelona, Spain.
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12
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Steuber TD, Howard ML, Nisly SA. Direct Oral Anticoagulants in Chronic Liver Disease. Ann Pharmacother 2019; 53:1042-1049. [PMID: 30947523 DOI: 10.1177/1060028019841582] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Objective: To review the use of direct oral anticoagulants (DOACs) in patients with chronic liver disease (CLD). Data Sources: A MEDLINE literature search was performed from 1964 through February 2019 using the following search terms: cirrhosis, chronic liver disease, direct oral anticoagulant, and the individual DOACs. Study Selection and Data Extraction: All English-language human trials and reports that examined DOACs for treatment or prevention of venous thromboembolic (VTE) events in patients with CLD were included. Data Synthesis: A total of 6 clinical trials examining the use of DOACs in patients with CLD were identified. All DOACs have been utilized in patients with CLD, with the exception of betrixaban, for prevention of stroke in atrial fibrillation or treatment of VTE (except for treatment of pulmonary embolism). The studies primarily evaluated patients with mild to moderate liver disease (Child-Turcotte-Pugh class A and B). The DOACs had similar rates of bleeding compared with traditional anticoagulants. Relevance to Patient Care and Clinical Practice: This review evaluates and summarizes the available evidence on DOACs in the setting of CLD. These agents may be more appealing in this population because monitoring or administration may be difficult with traditional anticoagulants (warfarin or low-molecular-weight heparins). Conclusion: Early data suggest that DOACs may be safe in patients with mild to moderate CLD. Should a DOAC be selected as an alternative to traditional anticoagulants, more frequent monitoring should be used because hepatotoxicity may be a concern. Larger clinical trials are needed to address efficacy outcomes as well as differences among individual DOACs in this population.
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Affiliation(s)
- Taylor D Steuber
- 1 Auburn University Harrison School of Pharmacy, Huntsville, AL, USA
| | - Meredith L Howard
- 2 University of North Texas System College of Pharmacy, Fort Worth, TX, USA
| | - Sarah A Nisly
- 3 Wingate University School of Pharmacy, Wingate, NC, USA
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13
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Davis KA, Puleo CR, Kovalic AJ, Nisly SA. Efficacy and safety of direct oral anticoagulant therapy for the treatment of venous thromboembolism in patients with chronic liver disease. Thromb Res 2019; 176:27-29. [PMID: 30769189 DOI: 10.1016/j.thromres.2019.02.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Revised: 01/08/2019] [Accepted: 02/02/2019] [Indexed: 10/27/2022]
Affiliation(s)
- Kyle A Davis
- Department of Pharmacy, Wake Forest Baptist Medical Center, Medical Center Blvd, Winston Salem, NC 27157, United States of America.
| | - Charles R Puleo
- Fred Wilson School of Pharmacy, High Point University, High Point, NC, United States of America
| | - Alexander J Kovalic
- Department of Internal Medicine, Wake Forest Baptist Medical Center, Medical Center Blvd, Winston Salem, NC 27157, United States of America
| | - Sarah A Nisly
- Wingate University School of Pharmacy, Clinical Pharmacy Specialist, Internal Medicine, Wake Forest Baptist Health, 515 N Main St, Wingate, NC 28174, United States of America.
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14
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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. [PMID: 29886103 DOI: 10.1016/j.vph.2018.05.002] [Citation(s) in RCA: 123] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2018] [Revised: 04/09/2018] [Accepted: 05/09/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Anticoagulation therapy is the main line of treatment for acute portal vein thrombosis (PVT) in the absence of cirrhosis. However, the use of this therapy in cirrhotic PVT is still with doubtful evidence. We aimed to evaluate the efficacy and safety of rivaroxaban compared to warfarin for the management of acute non-neoplastic PVT in Hepatitis C virus (HCV)-related compensated cirrhosis. METHODS Out of 578 patients with chronic HCV infection, 80 patients with acute PVT who had undergone splenectomy due to hypersplenism and 4 patients with acute PVT due to portal pyemia were selected. The patients were randomly assigned (1:1) to the study group (n = 40), in which the patients received rivaroxaban 10 mg/12 h, or the control group (n = 40), in which the patients received warfarin. RESULTS In the rivaroxaban group, the resolution of PVT was achieved in 34 patients (85%) within 2.6 ± 0.4 months and delayed, partial recanalization after 6.7 ± 1.2 months (n = 6.15%). Complications such as major bleeding, abnormal liver functions, death, or recurrence did not occur during treatment, and patients in this group showed improved short-term survival rate (20.4 ± 2.2 months) compared to the survival rate in the control group (10.6 ± 1.8 months) in which warfarin achieved complete resolution in 45% of patients. Complications such as severe upper GI tract bleeding (43.3%), hepatic decompensation (22.5%), progression to mesenteric ischemia (12.5%), recurrence (10%), and death (20%) were observed in the control group. The duration until complete resolution of thrombus correlated with age, the extent of the thrombus, creatinine level, and MELD score. The recurrence after complete resolution of thrombus correlated with age, the extent of the thrombus, thrombogenic gene polymorphism, and the use of warfarin. CONCLUSION Rivaroxaban was effective and safe in acute HCV-related non-neoplastic PVT with improved short-term survival rate; ClinicalTrials.gov Identifier: NCT03201367.
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Affiliation(s)
- Amr Shaaban Hanafy
- Internal Medicine Department, Hepatology Division, Zagazig University, Egypt.
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15
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Direct Oral Anticoagulants in Cirrhotic Patients: Current Evidence and Clinical Observations. Can J Gastroenterol Hepatol 2019; 2019:4383269. [PMID: 30792971 PMCID: PMC6354142 DOI: 10.1155/2019/4383269] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2018] [Revised: 12/17/2018] [Accepted: 12/26/2018] [Indexed: 02/07/2023] Open
Abstract
The introduction of Direct Oral Anticoagulants (DOACs) to the pharmaceutical market provided patients and clinicians with novel convenient and safe options of anticoagulation. The use of this class of medications is currently limited to venous thromboembolic therapy and prophylaxis, in addition to stroke prophylaxis in patients with nonvalvular atrial fibrillation. Despite their altered hemostasis, patients with cirrhosis are thought to be in a procoagulant state and thus prone to thrombus formation. Patients with cirrhosis might benefit from the convenience of DOACs; however, the medical literature includes limited data on the efficacy and safety of DOACs in this special patient population. The aim of this review is to summarize the current evidence for anticoagulation options in patients with cirrhosis and their safety profile.
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Abstract
BACKGROUND AND OBJECTIVE Portal vein thrombosis (PVT) is a common complication in cirrhosis, and when complete, it increases morbidity and mortality in liver transplant candidates. The aim of the study was to assess the hemostatic status, as well as clinical characteristics of thrombus and patients, as predictors of therapeutic efficacy of anticoagulation for the treatment of PVT in cirrhotics. PATIENTS AND METHODS Patients with cirrhosis consecutively treated for PVT with enoxaparin were enrolled. All patients underwent evaluation of coagulation status and thrombophilia screening. Thrombus characteristics and extension were evaluated at baseline and during follow-up. Anticoagulation was continued until recanalization or up to 12 months. Variables correlated with the response to anticoagulation were used to create a predictive score that was validated in an external multicenter cohort. RESULTS A total of 65 patients were included and had partial PVT in most cases (72%). Treatment with enoxaparin resulted in an overall response rate of 66% (43/65) after a median time of 4.4 months and 76% (33/43) within the first 6 months. At multivariate analysis, efficacy of anticoagulation correlated with the severity of liver disease, complete verus partial PVT, age of the thrombus, and time interval from treatment start (<6 months). The areas under the curve of the statistical model for predicting the response to anticoagulation were 0.84 and 0.76 for the training (n=65) and validation (n=60) cohorts, respectively. CONCLUSION Early diagnosis and early treatment are key factors for the successful management of PVT in cirrhosis, so that screening of PVT and prompt start of anticoagulant treatment should be mandatory.
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17
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Hypercoagulability in End-stage Liver Disease: Review of Epidemiology, Etiology, and Management. Transplant Direct 2018; 4:e403. [PMID: 30534594 PMCID: PMC6233657 DOI: 10.1097/txd.0000000000000843] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Accepted: 09/23/2018] [Indexed: 12/14/2022] Open
Abstract
In this review, we analyze the epidemiology of thromboses related to end-stage liver disease (ESLD), discuss causes of hypercoagulability, describe susceptible populations, and critically evaluate proposed prophylaxis and treatment of thromboses. Classically, ESLD has been regarded as a model for coagulopathy, and patients were deemed to be at high risk for bleeding complications. Patients with ESLD are not auto-anticoagulated, and they do not have a lower risk of portal vein thrombosis, intracardiac thrombus formation, pulmonary embolism or hepatic artery thrombosis. Though the cause of hypercoagulability is multifactorial, endothelial dysfunction likely plays a central role for all patients with ESLD. Some subpopulations, such as patients with nonalcoholic steatohepatitis and autoimmune conditions, are at increased risk of thrombotic events as are patients of Hispanic ethnicity. The science behind prophylaxis of different types of clotting and treatment of thromboses is developing rapidly. A number of medications, including low molecular weight heparin, unfractionated heparin, aspirin, vitamin K antagonists, and direct oral anticoagulants can be used, but clear guidelines are lacking. Acute intraoperative clotting can be associated with high mortality. Routine use of transesophageal echocardiography can be helpful in early recognition and treatment of intraoperative thrombosis. Heparin should be reserved for cases of intracardiac thrombus/pulmonary embolism without hemodynamic instability. In unstable patients, low dose of recombinant tissue plasminogen activator can be used. In this new era of heightened awareness of thrombotic events in ESLD patients, prospective randomized trials are urgently needed to best guide clinical practice.
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18
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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; 118:1491-1506. [PMID: 30060258 PMCID: PMC6202935 DOI: 10.1055/s-0038-1666861] [Citation(s) in RCA: 130] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Accepted: 05/17/2018] [Indexed: 12/12/2022]
Affiliation(s)
- N. M. Intagliata
- Department of Gastroenterology and Hepatology, University of Virginia, Charlottesville, Virginia, United States
| | - C. K. Argo
- Department of Gastroenterology and Hepatology, University of Virginia, Charlottesville, Virginia, United States
| | - J. G. Stine
- Department of Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania, United States
| | - T. Lisman
- Department of Surgery, University Medical Centre Groningen, Groningen, The Netherlands
| | - S. H. Caldwell
- Department of Gastroenterology and Hepatology, University of Virginia, Charlottesville, Virginia, United States
| | - F. Violi
- I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
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19
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Pant A, Kopec AK, Luyendyk JP. Role of the blood coagulation cascade in hepatic fibrosis. Am J Physiol Gastrointest Liver Physiol 2018; 315:G171-G176. [PMID: 29723040 PMCID: PMC6139645 DOI: 10.1152/ajpgi.00402.2017] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Revised: 04/19/2018] [Accepted: 04/24/2018] [Indexed: 02/07/2023]
Abstract
Liver is the primary source of numerous proteins that are critical for normal function of the blood coagulation cascade. Because of this, diseases of the liver, particularly when affiliated with severe complications like cirrhosis, are associated with abnormalities of blood clotting. Although conventional interpretation has inferred cirrhosis as a disorder of uniform bleeding risk, it is now increasingly appreciated as a disease wherein the coagulation cascade is precariously rebalanced. Moreover, prothrombotic risk factors are also associated with a more rapid progression of fibrosis in humans, suggesting that coagulation proteases participate in disease pathogenesis. Indeed, strong evidence drawn from experimental animal studies indicates that components of the coagulation cascade, particularly coagulation factor Xa and thrombin, drive profibrogenic events, leading to hepatic fibrosis. Here, we concisely review the evidence supporting a pathologic role for coagulation in the development of liver fibrosis and the potential mechanisms involved. Further, we highlight how studies in experimental animals may shed light on emerging clinical evidence, suggesting that beneficial effects of anticoagulation could extend beyond preventing thrombotic complications to include reducing pathologies like fibrosis.
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Affiliation(s)
- Asmita Pant
- Department of Pathobiology and Diagnostic Investigation, Michigan State University , East Lansing, Michigan
- Institute for Integrative Toxicology, Michigan State University , East Lansing, Michigan
| | - Anna K Kopec
- Department of Pathobiology and Diagnostic Investigation, Michigan State University , East Lansing, Michigan
- Institute for Integrative Toxicology, Michigan State University , East Lansing, Michigan
| | - James P Luyendyk
- Department of Pathobiology and Diagnostic Investigation, Michigan State University , East Lansing, Michigan
- Institute for Integrative Toxicology, Michigan State University , East Lansing, Michigan
- Department of Pharmacology and Toxicology, Michigan State University , East Lansing, Michigan
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20
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Bertoletti L, Benhamou Y, Béjot Y, Marechaux S, Cheggour S, Aleil B, Lellouche N, Dillinger JG, Delluc A. Direct oral anticoagulant use in patients with thrombophilia, antiphospholipid syndrome or venous thrombosis of unusual sites: A narrative review. Blood Rev 2018; 32:272-279. [DOI: 10.1016/j.blre.2018.01.002] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Revised: 12/06/2017] [Accepted: 01/23/2018] [Indexed: 12/19/2022]
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21
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Mantaka A, Augoustaki A, Kouroumalis EA, Samonakis DN. Portal vein thrombosis in cirrhosis: diagnosis, natural history, and therapeutic challenges. Ann Gastroenterol 2018; 31:315-329. [PMID: 29720857 PMCID: PMC5924854 DOI: 10.20524/aog.2018.0245] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Accepted: 11/26/2017] [Indexed: 12/13/2022] Open
Abstract
Portal vein thrombosis (PVT) is a frequent complication in cirrhosis and its prevalence increases with disease severity. Several factors are involved in the development and progression of PVT. The challenge for the management of PVT is the precise evaluation of the bleeding risk as opposed to life-threatening extension of thrombosis. Nevertheless, the impact on the progression and outcome of liver disease is unclear. A critical evaluation of the available data discloses that treating PVT in cirrhotics is safe and effective. However, there are open issues, such as which anticoagulant could represent a safer therapeutic option, and when and for how long this treatment should be administered to cirrhotic patients with PVT.
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Affiliation(s)
- Aikaterini Mantaka
- Department of Gastroenterology and Hepatology, University Hospital of Crete, Heraklion, Crete, Greece
| | - Aikaterini Augoustaki
- Department of Gastroenterology and Hepatology, University Hospital of Crete, Heraklion, Crete, Greece
| | - Elias A Kouroumalis
- Department of Gastroenterology and Hepatology, University Hospital of Crete, Heraklion, Crete, Greece
| | - Dimitrios N Samonakis
- Department of Gastroenterology and Hepatology, University Hospital of Crete, Heraklion, Crete, Greece
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22
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Maiwall R, Sarin SK. Extrahepatic Portal Vein Obstruction: Asian and Global Perspective. DIAGNOSTIC METHODS FOR CIRRHOSIS AND PORTAL HYPERTENSION 2018:271-300. [DOI: 10.1007/978-3-319-72628-1_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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23
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Saeian K, Kohli A, Ahn J. Portal Hypertensive Gastrointestinal Bleeding. HEPATIC CRITICAL CARE 2018:121-136. [DOI: 10.1007/978-3-319-66432-3_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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24
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Violi F, Lisman T. Cirrhosis as a risk factor for venous thrombosis. Thromb Haemost 2017; 117:3-5. [DOI: 10.1160/th16-10-0782] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2016] [Accepted: 10/14/2016] [Indexed: 02/07/2023]
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25
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Martín-Llahí M, Albillos A, Bañares R, Berzigotti A, García-Criado MÁ, Genescà J, Hernández-Gea V, Llop-Herrera E, Masnou-Ridaura H, Mateo J, Navascués CA, Puente Á, Romero-Gutiérrez M, Simón-Talero M, Téllez L, Turon F, Villanueva C, Zarrabeitia R, García-Pagán JC. Enfermedades vasculares del hígado. Guías Clínicas de la Sociedad Catalana de Digestología y de la Asociación Española para el Estudio del Hígado. GASTROENTEROLOGIA Y HEPATOLOGIA 2017; 40:538-580. [PMID: 28610817 DOI: 10.1016/j.gastrohep.2017.03.011] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Accepted: 03/29/2017] [Indexed: 12/11/2022]
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Raschi E, Bianchin M, De Ponti R, De Ponti F, Ageno W. Emerging therapeutic uses of direct-acting oral anticoagulants: An evidence-based perspective. Pharmacol Res 2017; 120:206-218. [PMID: 28366835 DOI: 10.1016/j.phrs.2017.03.026] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Revised: 03/22/2017] [Accepted: 03/29/2017] [Indexed: 12/24/2022]
Abstract
Direct-acting oral anticoagulants (DOACs) were claimed to cause a potential paradigm shift in the therapeutic scenario of patients requiring short- and long-term anticoagulation, by virtue of their pharmacological properties, perceived as innovative. The evidence gathered so far (from pre-approval pivotal trials to real-world post-marketing observational data) consistently confirmed that DOACs are overall comparable to vitamin-K antagonists (VKAs) in terms of safety, efficacy and effectiveness and unequivocally documented a consistent and clinically relevant reduced risk of intracranial bleeding in the settings of non-valvular atrial fibrillation (NVAF) and venous thromboembolism (VTE). Interestingly, two parallel paths can be identified in the current research scenario: A) in the aforementioned consolidated therapeutic indications, an innovative approach is directed towards tailored treatment strategies, to identify patients most likely to benefit from one of the different anticoagulant drugs, in particular subpopulations at increased risk of adverse events (e.g., bleeding); B) in unconventional settings, DOACs are gaining interest for potential use in emerging diseases characterized by arterial and venous thromboembolic risk. In these scenarios, the risk-benefit profile of DOACs, as compared to VKAs or heparins, is less defined. The aim of this review is to critically assess the body of evidence underlying emerging therapeutic uses of DOACs (e.g., heparin-induced thrombocytopenia, anti-phospholipid antibody syndrome), including evolving issues in special populations (e.g., patients with VTE and cancer or cirrhosis). This will be achieved by analyzing the strength (i.e., systematic reviews, randomized clinical trials, observational studies, case report/series) and consistency (i.e., concordance) of both published and unpublished evidence registered in major public repositories.
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Affiliation(s)
- Emanuel Raschi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Matteo Bianchin
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Roberto De Ponti
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Fabrizio De Ponti
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
| | - Walter Ageno
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
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27
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De Gottardi A, Trebicka J, Klinger C, Plessier A, Seijo S, Terziroli B, Magenta L, Semela D, Buscarini E, Langlet P, Görtzen J, Puente A, Müllhaupt B, Navascuès C, Nery F, Deltenre P, Turon F, Engelmann C, Arya R, Caca K, Peck-Radosavljevic M, Leebeek FWG, Valla D, Garcia-Pagan JC. Antithrombotic treatment with direct-acting oral anticoagulants in patients with splanchnic vein thrombosis and cirrhosis. Liver Int 2017; 37:694-699. [PMID: 27778440 DOI: 10.1111/liv.13285] [Citation(s) in RCA: 174] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2016] [Accepted: 10/18/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Direct-acting oral anticoagulants (DOACs) are used in patients with splanchnic vein thrombosis (SVT) and cirrhosis, but evidence for safety and efficacy in this setting is limited. Our aim was to identify indications and reasons for starting or switching to DOACs and to report adverse effects, complications and short-term outcome. METHODS Data collection including demographic information, laboratory values, treatment and complications through the Vascular Liver Disease Interest Group Consortium. RESULTS Forty-five centres (90%) of the consortium completed the initial eCRF. We report here a series of 94 patients from 17 centres. Thirty-six patients (38%) had cirrhosis. Child-Pugh score was 6 (range 5-8), and MELD score 10.2 (range 6-19). Indications for anticoagulation were splanchnic vein thrombosis (75%), deep vein thrombosis (5%), atrial fibrillation (14%) and others (6%). DOACs used were rivaroxaban (83%), dabigatran (11%) and apixaban (6%). Patients were followed up for a median duration of 15 months (cirrhotic) and 26.5 months (non-cirrhotic). Adverse events occurred in 17% of patients and included one case of recurrent portal vein thrombosis and five cases of bleeding. Treatment with DOACs was stopped in three cases. The major reasons for choosing DOACs were no need for monitoring or inadequacy of INR to guide anticoagulation in cirrhotic patients. Renal and liver function did not change during treatment. CONCLUSIONS A consistent number of patients with SVT and/or cirrhosis are currently treated with DOACs, which seem to be effective and safe. These data provide a basis for performing randomized clinical trials of DOACs vs. low molecular weight heparin or vitamin K antagonists.
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Affiliation(s)
- Andrea De Gottardi
- Hepatology, Department of Clinical Research and Clinic of Visceral Surgery and Medicine, Inselspital, University of Berne, Berne, Switzerland
| | | | | | | | | | | | | | - David Semela
- Kantonsspital St. Gallen, St. Gallen, Switzerland
| | | | | | | | - Angela Puente
- HUMV and Investigation Institute Marques de Valdecilla, Santander, Spain
| | | | | | | | | | - Fanny Turon
- Hospital Clinic, IDIBAPS and CIBERehd, Barcelona, Spain
| | | | | | - Karel Caca
- Klinikum Ludwigsburg, Ludwigsburg, Germany
| | | | - Frank W G Leebeek
- Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands
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Liew A, Douketis J. Portal vein thrombosis in patients with cirrhosis: underdiagnosis and undertreatment? Intern Emerg Med 2016; 11:1037-1040. [PMID: 27216797 DOI: 10.1007/s11739-016-1463-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2016] [Accepted: 05/06/2016] [Indexed: 01/17/2023]
Affiliation(s)
- Aaron Liew
- Portiuncula University Hospital & Galway University Hospital, Saolta University Health Care Group, Galway, Ireland
- National University of Ireland Galway (NUIG), Galway, Ireland
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
| | - James Douketis
- St. Joseph's Healthcare, Department of Medicine, McMaster University, F-544, 50 Charlton Ave East, Hamilton, ON, L8N 4A6, Canada.
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30
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Intagliata NM, Ferreira CN, Caldwell SH. Anticoagulación en la trombosis de la vena porta en la cirrosis. Clin Liver Dis (Hoboken) 2016; 8:S10-S15. [PMID: 31041089 PMCID: PMC6490226 DOI: 10.1002/cld.599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2015] [Accepted: 03/14/2016] [Indexed: 02/04/2023] Open
Affiliation(s)
- Nicolas M. Intagliata
- Division of Gastroenterology and Hepatology, Center for Coagulation in Liver DiseaseUniversity of Virginia Medical CenterCharlottesvilleVA, EE. UU., y
| | - Carlos N. Ferreira
- Servico de Gastrenterologia e Hepatologia, Hospital de Santa MariaCentro Hospitalar Lisboa NorteLisboaPortugal
| | - Stephen H. Caldwell
- Division of Gastroenterology and Hepatology, Center for Coagulation in Liver DiseaseUniversity of Virginia Medical CenterCharlottesvilleVA, EE. UU., y
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Abstract
BACKGROUND Portal vein thrombosis (PVT) is a complication of cirrhosis. However, whether PVT worsens cirrhosis outcome is a debated issue. AIM To report an update on the management of PVT. METHODS A review was performed on the outcome, prevention, and treatment of PVT. RESULTS Some studies suggest that PVT could worsen the rate of hepatic decompensation and survival of cirrhosis, whereas others report a non-negative impact of PVT in the outcome of cirrhosis. Therefore, the prognostic value of PVT in cirrhosis remains a gray zone. One single randomized-controlled trial reported that enoxaparin could prevent PVT, delay the occurrence of hepatic decompensation, and improve survival. However, no further study data confirmed this assumption and the issue is not actually generalizable. Numerous studies report that anticoagulation determines a relatively high rate of portal vein recanalization in cirrhotics PVT. However, further data are warranted to confirm the risk-to-benefit of anticoagulation, especially bleeding. Transjugular intrahepatic portosystemic shunt (TIPS) has been reported to be effective as a treatment of PVT in cirrhosis, with the advantage of avoiding the risk of bleeding linked to anticoagulation. However, there are no data comparing TIPS with anticoagulation as a treatment of PVT in cirrhosis. Furthermore, there is no evidence on whether both anticoagulation and TIPS improve survival. CONCLUSION It is uncertain whether PVT affects cirrhosis outcome. Further data are needed to weigh the risk/benefit ratio of enoxaparin for the prevention of PVT in cirrhosis. Anticoagulation or TIPS should probably be indicated in liver transplantation candidates, but avoided in patients not suitable for liver transplantation and with an otherwise poor prognosis. Future studies should evaluate which subgroup of cirrhotics with PVT may benefit from treatment. Management of PVT in cirrhosis should be personalized.
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Intagliata NM, Ferreira CN, Caldwell SH. Anticoagulation for portal vein thrombosis in cirrhosis. Clin Liver Dis (Hoboken) 2016; 7:126-131. [PMID: 31041046 PMCID: PMC6490275 DOI: 10.1002/cld.552] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2015] [Revised: 02/24/2016] [Accepted: 03/14/2016] [Indexed: 02/04/2023] Open
Affiliation(s)
- Nicolas M. Intagliata
- Division of Gastroenterology and Hepatology, Center for Coagulation in Liver DiseaseUniversity of Virginia Medical CenterCharlottesvilleVA
| | - Carlos N. Ferreira
- Servico de Gastrenterologia e Hepatologia, Hospital de Santa MariaCentro Hospitalar Lisboa NorteLisbonPortugal
| | - Stephen H. Caldwell
- Division of Gastroenterology and Hepatology, Center for Coagulation in Liver DiseaseUniversity of Virginia Medical CenterCharlottesvilleVA
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Intagliata NM, Henry ZH, Maitland H, Shah NL, Argo CK, Northup PG, Caldwell SH. Direct Oral Anticoagulants in Cirrhosis Patients Pose Similar Risks of Bleeding When Compared to Traditional Anticoagulation. Dig Dis Sci 2016; 61:1721-7. [PMID: 26725062 DOI: 10.1007/s10620-015-4012-2] [Citation(s) in RCA: 191] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2015] [Accepted: 12/14/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Direct oral anticoagulants (DOAC) are important new anticoagulant therapies that are not well studied in patients with chronic liver disease. The aim of this study was to compare rates of bleeding in cirrhosis patients treated with DOAC (factor Xa inhibitors: rivaroxaban and apixaban) to those in cirrhosis patients treated with traditional anticoagulation (warfarin and low molecular weight heparin). METHODS We identified a total of 39 patients with cirrhosis who received anticoagulation therapy over a 3-year period (20 DOAC and 19 traditional anticoagulation) from a research database. Medical records were reviewed to obtain clinical data to compare between the groups. RESULTS Clinical characteristics between the two groups were similar. There were three documented bleeding events in the traditional anticoagulation group and four bleeding events in the DOAC group (p = 0.9). There were two major bleeding events in the traditional anticoagulation group and one major bleeding event in the DOAC group. There were no documented reports of drug-induced liver injury during this study period. Among all patients, no significant predictors of bleeding were identified using univariate regression and Cox proportional hazard modeling. CONCLUSIONS This is the first clinical study evaluating the use of DOAC in patients with cirrhosis. DOAC display similar safety characteristics when compared to traditional anticoagulation in patients with cirrhosis and are potentially attractive agents for anticoagulation therapy. Larger studies are now needed to better understand the safety and efficacy of these agents in cirrhosis.
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Affiliation(s)
- N M Intagliata
- Coagulation in Liver Disease Study Group, Division of Gastroenterology and Hepatology, University of Virginia Medical Center, PO Box 800708, Charlottesville, VA, 22908, USA.
| | - Z H Henry
- Coagulation in Liver Disease Study Group, Division of Gastroenterology and Hepatology, University of Virginia Medical Center, PO Box 800708, Charlottesville, VA, 22908, USA
| | - H Maitland
- Division of Hematology and Oncology, University of Virginia Medical Center, PO Box 800716, Charlottesville, VA, 22908, USA
| | - N L Shah
- Coagulation in Liver Disease Study Group, Division of Gastroenterology and Hepatology, University of Virginia Medical Center, PO Box 800708, Charlottesville, VA, 22908, USA
| | - C K Argo
- Coagulation in Liver Disease Study Group, Division of Gastroenterology and Hepatology, University of Virginia Medical Center, PO Box 800708, Charlottesville, VA, 22908, USA
| | - P G Northup
- Coagulation in Liver Disease Study Group, Division of Gastroenterology and Hepatology, University of Virginia Medical Center, PO Box 800708, Charlottesville, VA, 22908, USA
| | - S H Caldwell
- Coagulation in Liver Disease Study Group, Division of Gastroenterology and Hepatology, University of Virginia Medical Center, PO Box 800708, Charlottesville, VA, 22908, USA
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Abstract
OPINION STATEMENT The risk of thrombosis in patients with chronic liver disease is increasingly recognized. As patients with cirrhosis develop indications for anticoagulation therapy (e.g., venous thromboembolism, portal vein thrombosis, or atrial fibrillation), providers are left to make difficult decisions when selecting therapeutics with little evidence to rely on. Current practice supports the use of low molecular weight heparin or vitamin K antagonists in select patients with cirrhosis requiring anticoagulation. While traditional anticoagulants may be safe and effective in select patients with compensated cirrhosis, the use of direct oral anticoagulants (DOAC) is more controversial. DOAC are desirable as they do not require routine monitoring and can be taken orally. Unfortunately, patients with chronic liver disease were excluded from clinical trials that demonstrated efficacy and safety when compared to traditional anticoagulation. Data are now emerging that support the use of DOAC in well-compensated cirrhosis patients. However, further study is needed with all (traditional and DOAC) anticoagulation medications in patients with cirrhosis to better ensure safety and further understand pharmacologic properties in this challenging population.
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Affiliation(s)
- Nicolas M Intagliata
- Division of Gastroenterology and Hepatology, Center for Coagulation in Liver Disease, University of Virginia Medical Center, PO Box 800708, Charlottesville, VA, USA.
| | - Hillary Maitland
- Division of Hematology, University of Virginia Medical Center, Charlottesville, VA, USA
| | - Stephen H Caldwell
- Division of Gastroenterology and Hepatology, Center for Coagulation in Liver Disease, University of Virginia Medical Center, PO Box 800708, Charlottesville, VA, USA
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35
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Finazzi G, Ageno W. Direct oral anticoagulants in rare venous thrombosis. Intern Emerg Med 2016; 11:167-70. [PMID: 26875179 DOI: 10.1007/s11739-016-1398-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Accepted: 01/19/2016] [Indexed: 12/12/2022]
Abstract
The direct inhibitors of thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban) are currently used in patients with venous thrombosis of the lower or upper limbs or with pulmonary embolism. However, the use of these direct oral anticoagulants (DOACs) in subjects with abdominal or cerebral venous thrombosis is more contentious due to the paucity of available data. In a few case reports and small series of patients hitherto published, the DOACs showed good efficacy and safety, supporting an extension of their use to these rare conditions. Thus, prospective cohort studies and randomized controlled trials have been set up. In this article, we review the published clinical experience with DOACs in rare venous thrombosis, and provide updated information on ongoing clinical trials.
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Affiliation(s)
- Guido Finazzi
- USS Malattie Mieloproliferative Croniche, USC Ematologia, Ospedale Papa Giovanni XXIII, Piazza OMS 1, 24127, Bergamo, Italy.
| | - Walter Ageno
- Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi dell'Insubria, Varese, Italy
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36
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Chen H, Turon F, Hernández-Gea V, Fuster J, Garcia-Criado A, Barrufet M, Darnell A, Fondevila C, Garcia-Valdecasas JC, Garcia-Pagán JC. Nontumoral portal vein thrombosis in patients awaiting liver transplantation. Liver Transpl 2016; 22:352-65. [PMID: 26684272 DOI: 10.1002/lt.24387] [Citation(s) in RCA: 101] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Revised: 11/06/2015] [Accepted: 11/25/2015] [Indexed: 02/06/2023]
Abstract
Portal vein thrombosis (PVT) occurs in approximately 2%-26% of the patients awaiting liver transplantation (LT) and is no longer an absolute contraindication for LT. Nearly half of PVT cases are accidentally found during the LT procedure. The most important risk factor for PVT development in cirrhosis may be the severity of liver disease and reduced portal blood flow. Whether other inherited or acquired coagulation disorders also play a role is not yet clear. The development of PVT may have no effect on the liver disease progression, especially when it is nonocclusive. PVT may not increase the risk of wait-list mortality, but it is a risk factor for poor early post-LT mortality. Anticoagulation and transjugular intrahepatic portosystemic shunt (TIPS) are 2 major treatment strategies for patients with PVT on the waiting list. The complete recanalization rate after anticoagulation is approximately 40%. The role of TIPS to maintain PV patency for LT as the primary indication has been reported, but the safety and efficacy should be further evaluated. PVT extension and degree may determine the surgical technique to be used during LT. If a "conventional" end-to-end portal anastomotic technique is used, there is not a major impact on post-LT survival. Post-LT PVT can significantly reduce both graft and patient survival after LT and can preclude future options for re-LT.
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Affiliation(s)
- Hui Chen
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Barcelona, Spain
| | - Fanny Turon
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain
| | - Virginia Hernández-Gea
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain
| | - Josep Fuster
- HBP Surgery and Liver Transplantation Unit, University of Barcelona, Barcelona, Spain
| | - Angeles Garcia-Criado
- Department of Radiology, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
| | - Marta Barrufet
- Department of Radiology, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
| | - Anna Darnell
- Department of Radiology, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
| | - Constantino Fondevila
- HBP Surgery and Liver Transplantation Unit, University of Barcelona, Barcelona, Spain
| | | | - Juan Carlos Garcia-Pagán
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain
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Stine JG, Shah PM, Cornella SL, Rudnick SR, Ghabril MS, Stukenborg GJ, Northup PG. Portal vein thrombosis, mortality and hepatic decompensation in patients with cirrhosis: A meta-analysis. World J Hepatol 2015; 7:2774-2780. [PMID: 26644821 PMCID: PMC4663397 DOI: 10.4254/wjh.v7.i27.2774] [Citation(s) in RCA: 99] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2015] [Revised: 11/02/2015] [Accepted: 11/11/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the clinical impact of portal vein thrombosis in terms of both mortality and hepatic decompensations (variceal hemorrhage, ascites, portosystemic encephalopathy) in adult patients with cirrhosis.
METHODS: We identified original articles reported through February 2015 in MEDLINE, Scopus, Science Citation Index, AMED, the Cochrane Library, and relevant examples available in the grey literature. Two independent reviewers screened all citations for inclusion criteria and extracted summary data. Random effects odds ratios were calculated to obtain aggregate estimates of effect size across included studies, with 95%CI.
RESULTS: A total of 226 citations were identified and reviewed, and 3 studies with 2436 participants were included in the meta-analysis of summary effect. Patients with portal vein thrombosis had an increased risk of mortality (OR = 1.62, 95%CI: 1.11-2.36, P = 0.01). Portal vein thrombosis was associated with an increased risk of ascites (OR = 2.52, 95%CI: 1.63-3.89, P < 0.001). There was insufficient data available to determine the pooled effect on other markers of decompensation including gastroesophageal variceal bleeding or hepatic encephalopathy.
CONCLUSION: Portal vein thrombosis appears to increase mortality and ascites, however, the relatively small number of included studies limits more generalizable conclusions. More trials with a direct comparison group are needed.
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Abstract
Portal vein thrombosis is an unusual thrombotic condition not frequently seen in the general population; however, it has a higher prevalence in special circumstances such as in liver cirrhosis and hepatic or pancreatic malignancy. It also can be associated with significant morbidity and mortality. In this review, we discuss the current data available to guide therapy in the setting of different associated co-morbidities, hypercoagulable states, and associated thrombosis of the remaining splanchnic circulation. We discuss indications for anticoagulation, including the choice of anticoagulants, as well as the role of conservative 'wait and watch' and invasive therapies, such as thrombolysis, thrombectomy, and transjugular intrahepatic portosystemic shunt.
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Affiliation(s)
- Aditya M Sharma
- Division of Cardiovascular Medicine, University of Virginia, Charlottesville, VA, USA
| | - Daisy Zhu
- Medical Education, University of Virginia, Charlottesville, VA, USA
| | - Zachary Henry
- Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, VA, USA
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39
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Harding DJ, Perera MTPR, Chen F, Olliff S, Tripathi D. Portal vein thrombosis in cirrhosis: Controversies and latest developments. World J Gastroenterol 2015; 21:6769-6784. [PMID: 26078553 PMCID: PMC4462717 DOI: 10.3748/wjg.v21.i22.6769] [Citation(s) in RCA: 78] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2015] [Revised: 03/12/2015] [Accepted: 05/07/2015] [Indexed: 02/06/2023] Open
Abstract
Portal vein thrombosis (PVT) is encountered in liver cirrhosis, particularly in advanced disease. It has been a feared complication of cirrhosis, attributed to significant worsening of liver disease, poorer clinical outcomes and potential inoperability at liver transplantation; also catastrophic events such as acute intestinal ischaemia. Optimal management of PVT has not yet been addressed in any consensus publication. We review current literature on PVT in cirrhosis; its prevalence, pathophysiology, diagnosis, impact on the natural history of cirrhosis and liver transplantation, and management. Studies were identified by a search strategy using MEDLINE and Google Scholar. The incidence of PVT increases with increasing severity of liver disease: less than 1% in well-compensated cirrhosis, 7.4%-16% in advanced cirrhosis. Prevalence in patients undergoing liver transplantation is 5%-16%. PVT frequently regresses instead of uniform thrombus progression. PVT is not associated with increased risk of mortality. Optimal management has not been addressed in any consensus publication. We propose areas for future research to address unresolved clinical questions.
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40
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Simonetto DA, Wysokinski WE, Kamath PS. Use of nontraditional anticoagulants in portal vein thrombosis: a note of caution. Hepatology 2015; 61:2119. [PMID: 25266497 DOI: 10.1002/hep.27541] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Affiliation(s)
| | | | - Patrick S Kamath
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
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41
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Potze W, Adelmeijer J, Lisman T. Decreased in vitro anticoagulant potency of Rivaroxaban and Apixaban in plasma from patients with cirrhosis. Hepatology 2015; 61:1435-6. [PMID: 25088782 DOI: 10.1002/hep.27350] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2014] [Revised: 06/17/2014] [Accepted: 06/25/2014] [Indexed: 12/11/2022]
Affiliation(s)
- Wilma Potze
- Surgical Research Laboratory and Section of Hepatobiliary, Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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