|
1
|
Zhang J, Dang X, Zhang L, Li W. A pilot study of safety and efficacy comparison of low molecular heparin calcium sequential oral anticoagulants in the treatment of cirrhotic portal vein thrombosis. Eur J Gastroenterol Hepatol 2024; 36:1119-1125. [PMID: 39101441 DOI: 10.1097/meg.0000000000002787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/06/2024]
Abstract
BACKGROUND The objective of this study is to compare and assess the efficacy and safety of low-molecular-weight heparin calcium (LMWH-Ca), followed by either warfarin or rivaroxaban, as treatment options for portal vein thrombosis (PVT) in patients with cirrhosis. METHODS In this pilot study, cirrhotic (with liver function score of Child-Pugh A) patients diagnosed with PVT who were not on anticoagulant therapy received 2 weeks of subcutaneous injections of LMWH-Ca. They were then randomized to either warfarin (a full course of oral warfarin for 6 months) or rivaroxaban (a full course of oral rivaroxaban for 2 months), with 30 cases in each group. After a treatment period of up to 6 months, a comparative analysis was performed to assess the efficacy and safety of both groups. Volumetric changes in PVT were monitored dynamically using enhanced computed tomography scans before treatment at week 2 and month 6. RESULTS There were no statistically significant differences in the clinical characteristics of the patients between the two groups. Rivaroxaban treatment reduced PVT median volume from 1.83 cm3 at week 2 to 0.0 cm3 at month 6 and prevented the worsening of PVT after 6 months of treatment with LMWH-Ca (P < 0.001). On the other hand, warfarin treatment increased PVT median volume from 1.95 cm3 at week 2 to 3.78 cm3 at month 6 (P = 0.002). None of the 30 patients in the rivaroxaban group had clinically significant gastrointestinal bleeding, while 2 of the 30 patients (7%) in the warfarin group had gastrointestinal bleeding (P = 0.317). CONCLUSION Rivaroxaban followed by LMWH-Ca is an effective anticoagulant treatment strategy for PVT in cirrhosis.
Collapse
Affiliation(s)
- Jie Zhang
- Department of Hepatology, First Clinical Medical College, Shanxi Medical University, Third People's Hospital of Taiyuan City
| | - Xiaohong Dang
- Department of Gastroenterology, First Clinical Medical College, Shanxi Medical University
| | - Lijuan Zhang
- First Clinical Medical College, Shanxi Medical University, Wanbailin Branch, Imaging Centers, Taiyuan, Shanxi Province, China
| | - Wenhua Li
- Department of Hepatology, First Clinical Medical College, Shanxi Medical University, Third People's Hospital of Taiyuan City
| |
Collapse
|
|
2
|
Yagoda AV, Koroy PV, Baisaeva LS, Dudov TR. Portal Vein Thrombosis in Liver Cirrhosis. Part 2: Treatment, Primary and Secondary Prevention. THE RUSSIAN ARCHIVES OF INTERNAL MEDICINE 2024; 14:251-259. [DOI: 10.20514/2226-6704-2024-14-4-251-259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
In most cases, portal vein thrombosis progresses without treatment; spontaneous recanalization of portal vein develops in 42 % of patients with liver cirrhosis. Effective treatment strategies include administration of anticoagulants, interventional procedures such as transjugular intrahepatic porto-systemic shunt or endovascular fibrinolysis. Anticoagulant therapy has certain difficulties in patients with liver cirrhosis due to the complex profile of hemostasis, a tendency to both hemorrhages and hypercoagulation. In addition to traditional anticoagulants (heparin preparations, fondaparinux, vitamin K antagonists), direct oral anticoagulants have been widely used in recent years for portal vein thrombosis. Previously, portal vein thrombosis was considered a contraindication to performing transjugular intrahepatic porto-systemic shunt, currently the method is often used to restore portal blood flow through the shunt and prevent repeated thrombosis. Endovascular fibrinolysis is still an option for specialized centers for «difficult» patients. In cases of increased risk of venous thromboembolism, patients with liver cirrhosis are recommended to be prevented with low-molecular-weight heparin or direct oral anticoagulants, but further studies should clarify their effectiveness in this aspect. The review highlights data on the features of therapy, primary and secondary prevention of portal vein thrombosis in patients with liver cirrhosis. Despite the existing clinical recommendations for management of patients with cirrhotic portal vein thrombosis, the choice of a particular strategy primarily depends on an individualized assessment of risks and benefits of each treatment method.
Collapse
|
|
3
|
Alotay AA. Classification and Management of Portal Vein Thrombosis in Cirrhotic Patients: A Narrative Review. Cureus 2024; 16:e65869. [PMID: 39219865 PMCID: PMC11364363 DOI: 10.7759/cureus.65869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Accepted: 07/20/2024] [Indexed: 09/04/2024] Open
Abstract
Portal vein thrombosis (PVT) poses significant therapeutic challenges due to its complex pathophysiology and diverse clinical presentations. Recent advancements have spurred the development of new therapeutic approaches to enhance treatment efficacy and safety. This review synthesized emerging therapies for PVT based on a comprehensive literature search across major databases such as PubMed, EMBASE, and Web of Science, among others, focusing on studies published in the last decade. Anticoagulation therapy, particularly with novel oral anticoagulants (NOACs), emerged as beneficial in personalized treatment regimens. Innovative surgical techniques and improved risk stratification methods were identified as crucial in the perioperative management of PVT. Additionally, advances in cell therapy and medical treatments for hepatocellular carcinoma in the context of PVT were explored. Promising outcomes were observed with modalities such as Yttrium 90 and liver transplantation combined with thrombectomy, particularly in complex PVT cases associated with hepatocellular carcinoma, albeit on a limited scale. The reviewed literature indicates a shift towards individualized treatment approaches for PVT, integrating novel anticoagulants, refined risk assessment tools, and tailored interventional strategies. While these emerging therapies show potential for enhanced efficacy and safety, further research is essential to validate findings across broader patient populations and establish standardized treatment protocols.
Collapse
Affiliation(s)
- Abdulwahed A Alotay
- Department of Internal Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, SAU
| |
Collapse
|
|
4
|
Karvellas CJ, Bajaj JS, Kamath PS, Napolitano L, O'Leary JG, Solà E, Subramanian R, Wong F, Asrani SK. AASLD Practice Guidance on Acute-on-chronic liver failure and the management of critically ill patients with cirrhosis. Hepatology 2024; 79:1463-1502. [PMID: 37939273 DOI: 10.1097/hep.0000000000000671] [Citation(s) in RCA: 31] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 11/01/2023] [Indexed: 11/10/2023]
Affiliation(s)
- Constantine J Karvellas
- Division of Gastroenterology (Liver Unit), Department of Critical Care Medicine, University of Alberta, Edmonton, Canada
| | - Jasmohan S Bajaj
- Virginia Commonwealth University, Central Virginia Veterans Healthcare System, Richmond, Virginia, USA
| | - Patrick S Kamath
- Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA
| | | | - Jacqueline G O'Leary
- Department of Medicine, Dallas Veterans Medical Center, University of Texas Southwestern Medical Center Dallas, Texas, USA
| | - Elsa Solà
- Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California, USA
| | | | | | | |
Collapse
|
|
5
|
Diesveld MME, Pijnenburg DWMJ, Weersink RA, Barzel I, Drenth JPH, Lisman T, Metselaar HJ, Monster-Simons MH, Mulder MB, Okel E, Taxis K, Borgsteede SD. Recommendations for the safe use of direct oral anticoagulants in patients with cirrhosis based on a systematic review of pharmacokinetic, pharmacodynamic and safety data. Eur J Clin Pharmacol 2024; 80:797-812. [PMID: 38430266 DOI: 10.1007/s00228-024-03648-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 02/03/2024] [Indexed: 03/03/2024]
Abstract
PURPOSE The popularity of direct oral anticoagulants (DOACs) is increasing among patients with cirrhosis. Cirrhosis has a major impact on the pharmacokinetics of drugs, potentially increasing adverse events. Safe use of drugs in cirrhosis requires a diligent risk-benefit analysis. The aim of this study is to develop practice recommendations for safe use of DOACs in cirrhosis based on a systematic review of pharmacokinetic, pharmacodynamic and safety data. METHODS We conducted a systematic literature search to identify studies on pharmacokinetics, pharmacodynamics and safety of DOACs in cirrhosis. Data were collected and presented in summary tables by severity of cirrhosis using the Child-Turcotte-Pugh (CTP) classification. A multidisciplinary expert panel evaluated the results and classified the DOACs according to safety. RESULTS Fifty four studies were included. All DOACs were classified as 'no additional risks known' for CTP A. For CTP B, apixaban, dabigatran and edoxaban were classified as 'no additional risks known'. Apixaban and edoxaban showed fewer adverse events in patients with cirrhosis, while dabigatran may be less impacted by severity of cirrhosis based on its pharmacokinetic profile. Rivaroxaban was classified as 'unsafe' in CTP B and C based on significant pharmacokinetic alterations. Due to lack of data, apixaban, dabigatran and edoxaban were classified as 'unknown' for CTP C. CONCLUSION DOACs can be used in patients with CTP A cirrhosis, and apixaban, dabigatran and edoxaban can also be used in CTP B. It is recommended to avoid rivaroxaban in CTP B and C. There is insufficient evidence to support safe use of other DOACs in CTP C cirrhosis.
Collapse
Affiliation(s)
| | | | - Rianne A Weersink
- Deventer Hospital, Department of Clinical Pharmacy, Deventer, The Netherlands
- Radboud University Medical Center, Department of Pharmacy, Nijmegen, The Netherlands
| | - Ina Barzel
- Erasmus University Medical Center, Department of Hospital Pharmacy, Rotterdam, The Netherlands
| | - Joost P H Drenth
- Radboud University Medical Center, Department of Gastroenterology, Nijmegen, The Netherlands
| | - Ton Lisman
- University of Groningen, University Medical Center Groningen, Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Groningen, The Netherlands
| | - Herold J Metselaar
- Erasmus University Medical Center, Department of Gastroenterology and Hepatology, Rotterdam, The Netherlands
| | - Margje H Monster-Simons
- Dutch Medicines Evaluation Board, Utrecht, The Netherlands
- University of Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands
| | - Midas B Mulder
- Erasmus University Medical Center, Department of Hospital Pharmacy, Rotterdam, The Netherlands
| | - Eline Okel
- Pharmacy Zorgapotheken Flevoland, Almere, The Netherlands
| | - Katja Taxis
- University of Groningen, Groningen Research Institute of Pharmacy, Unit of Pharmacotherapy, -Epidemiology & -Economics, Groningen, The Netherlands
| | | |
Collapse
|
|
6
|
Eltweri AM, Basamh M, Ting YY, Harris M, Garcea G, Kuan LL. A retrospective multicentre clinical study on management of isolated splenic vein thrombosis: risks and benefits of anticoagulation. Langenbecks Arch Surg 2024; 409:116. [PMID: 38592545 PMCID: PMC11003905 DOI: 10.1007/s00423-024-03295-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2024] [Accepted: 03/21/2024] [Indexed: 04/10/2024]
Abstract
INTRODUCTION Isolated splenic vein thrombosis (iSVT) is a common complication of pancreatic disease. Whilst patients remain asymptomatic, there is a risk of sinistral portal hypertension and subsequent bleeding from gastric varices if recanalisation does not occur. There is wide variation of iSVT treatment, even within single centres. We report outcomes of iSVT from tertiary referral hepatobiliary and pancreatic (HPB) units including the impact of anticoagulation on recanalisation rates and subsequent variceal bleeding risk. METHODS A retrospective cohort study including all patients diagnosed with iSVT on contrast-enhanced CT scan abdomen and pelvis between 2011 and 2019 from two institutions. Patients with both SVT and portal vein thrombosis at diagnosis and isolated splenic vein thrombosis secondary to malignancy were excluded. The outcomes of anticoagulation, recanalisation rates, risk of bleeding and progression to portal vein thrombosis were examined using CT scan abdomen and pelvis with contrast. RESULTS Ninety-eight patients with iSVT were included, of which 39 patients received anticoagulation (40%). The most common cause of iSVT was acute pancreatitis n = 88 (90%). The recanalisation rate in the anticoagulation group was 46% vs 15% in patients receiving no anticoagulation (p = 0.0008, OR = 4.7, 95% CI 1.775 to 11.72). Upper abdominal vascular collaterals (demonstrated on CT scan angiography) were significantly less amongst patients who received anticoagulation treatment (p = 0.03, OR = 0.4, 95% CI 0.1736 to 0.9288). The overall rate of upper GI variceal-related bleeding was 3% (n = 3/98) and it was independent of anticoagulation treatment. Two of the patients received therapeutic anticoagulation. CONCLUSION The current data supports that therapeutic anticoagulation is associated with a statistically significant increase in recanalisation rates of the splenic vein, with a subsequent reduction in radiological left-sided portal hypertension. However, all patients had a very low risk of variceal bleeding regardless of anticoagulation. The findings from this retrospective study should merit further investigation in large-scale randomised clinical trials.
Collapse
Affiliation(s)
- A M Eltweri
- Hepatobiliary and Pancreatic Surgery Department, University Hospitals of Leicester, Leicester General Hospital, Leicester, UK.
| | - M Basamh
- Hepatobiliary and Pancreatic Surgery Department, University Hospitals of Leicester, Leicester General Hospital, Leicester, UK
| | - Y Y Ting
- Department of Surgery, The Queen Elizabeth Hospital, The University of Adelaide, Adelaide, South Australia, Australia
| | - M Harris
- Department of Surgery, The Queen Elizabeth Hospital, The University of Adelaide, Adelaide, South Australia, Australia
| | - G Garcea
- Hepatobiliary and Pancreatic Surgery Department, University Hospitals of Leicester, Leicester General Hospital, Leicester, UK
| | - L L Kuan
- Department of Surgery, The Queen Elizabeth Hospital, The University of Adelaide, Adelaide, South Australia, Australia
| |
Collapse
|
|
7
|
Calcaterra I, Tufano A, Strano F, Rufolo P, Donnarumma S, Palermo V, De Ruberto F, Cimino E, Guerrino C, Conca P, Iannuzzo G, Di Minno M. Efficacy and safety of direct oral anticoagulants in splanchnic vein thrombosis: a pooled analysis of literature studies. J Thromb Haemost 2024; 22:534-544. [PMID: 37926192 DOI: 10.1016/j.jtha.2023.10.023] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Revised: 10/18/2023] [Accepted: 10/22/2023] [Indexed: 11/07/2023]
Abstract
BACKGROUND Limited evidence is available on management of splanchnic vein thrombosis (SVT). OBJECTIVES This study aimed to evaluate safety and efficacy of direct oral anticoagulants (DOACs) for SVT treatment. METHODS Studies were systematically searched in the PubMed, Web of Science, and Scopus databases according to PRISMA guidelines. We assessed any recanalization, full recanalization, recurrence, mortality, and major bleeding as outcomes of interest. Results were reported as weighted mean prevalence (WMP) with 95% CI. Subgroup analyses and meta-regressions have been performed to address heterogeneity and adjust for potential confounders. RESULTS We included a total of 16 studies (17 datasets) on 648 patients with SVT treated with DOACs. We found any recanalization in 60.3% (95% CI: 41.8%-76.3%; I2 = 84.9%; P < .001) and full recanalization in 51.7% (95% CI: 36.0%-67.0%; I2 = 87.4%; P < .001). Recurrent venous thromboembolism occurred in 2.8% (95% CI: 1.4%-5.9%; I2 = 0%; P = .787) and death in 3.4% (95% CI: 1.6%-7.3%; I2 = 13.2%; P = .318) of patients. Major bleeding was reported by 5.8% (95% CI: 3.7%-8.9%; I2 = 29.2%; P = .125) of patients. Results were consistent when separately analyzing prospective studies, retrospective studies, studies on cirrhotic patients, and studies enrolling patients with portal vein thrombosis. Meta-regression analyses showed that an increasing age and cancer impacted the rate of recanalization. Cirrhosis was associated with a higher rate of major bleeding and mortality. CONCLUSION The results of the present study, mostly based on observational studies, suggest good safety and efficacy profiles of DOACs in patients with SVT. Randomized studies are needed to corroborate our findings.
Collapse
Affiliation(s)
- Ilenia Calcaterra
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Antonella Tufano
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Federica Strano
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Paola Rufolo
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Sofia Donnarumma
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Vincenzina Palermo
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Francesca De Ruberto
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Ernesto Cimino
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Cornelia Guerrino
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Paolo Conca
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Gabriella Iannuzzo
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Matteo Di Minno
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
| |
Collapse
|
|
8
|
Xiao X, Zhu W, Dai Q. Direct Oral Anticoagulants Versus Traditional Anticoagulation in Cirrhotic Patients with Portal Vein Thrombosis: Updated Systematic Review. Clin Appl Thromb Hemost 2024; 30:10760296241303758. [PMID: 39587933 PMCID: PMC11590147 DOI: 10.1177/10760296241303758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 11/01/2024] [Accepted: 11/11/2024] [Indexed: 11/27/2024] Open
Abstract
BACKGROUND This systematic review aimed to evaluate the comparative effectiveness and safety of direct oral anticoagulants (DOACs) compared to traditional anticoagulation (vitamin K antagonists or low-molecular-weight heparins) in cirrhotic patients with portal vein thrombosis (PVT). METHODS We conducted a literature search in PubMed and Embase databases up to May 2024. Studies were selected according to the PICOS criteria, focusing on cirrhotic patients with PVT treated with DOACs (dabigatran, rivaroxaban, apixaban, or edoxaban) compared to traditional anticoagulation. RESULTS Our systematic review included four observational studies conducted in Japan, China, and the United States, involving a total of 223 patients with cirrhosis and PVT. The included studies collectively suggested that anticoagulation therapy, including DOACs, was associated with improved recanalization rates and reduced progression of PVT in patients with liver cirrhosis, without a significant increase in bleeding complications. Specifically, edoxaban demonstrated superior effectiveness in reducing PVT volume compared to traditional anticoagulation, while maintaining a favorable safety profile. CONCLUSION DOACs may provide a promising therapeutic option for PVT in cirrhotic patients. Further research is needed to confirm the potential benefits and risks of DOACs in this population.
Collapse
Affiliation(s)
- Xiulin Xiao
- Department of Hepatopancreatobiliary Surgery, Ganzhou People's Hospital, Ganzhou, Jiangxi, China
| | - Wengen Zhu
- Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Qixin Dai
- Department of Hepatopancreatobiliary Surgery, Ganzhou People's Hospital, Ganzhou, Jiangxi, China
| |
Collapse
|
|
9
|
Aiza-Haddad I, Cisneros-Garza LE, Morales-Gutiérrez O, Malé-Velázquez R, Rizo-Robles MT, Alvarado-Reyes R, Barrientos-Quintanilla LA, Betancourt-Sánchez F, Cerda-Reyes E, Contreras-Omaña R, Dehesa-Violante MB, Flores-García NC, Gómez-Almaguer D, Higuera-de la Tijera MF, Lira-Pedrin MA, Lira-Vera JE, Manzano-Cortés H, Meléndez-Mena DE, Muñoz-Ramírez MR, Pérez-Hernández JL, Ramos-Gómez MV, Sánchez-Ávila JF. Guidelines for the management of coagulation disorders in patients with cirrhosis. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2024; 89:144-162. [PMID: 38600006 DOI: 10.1016/j.rgmxen.2023.08.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 08/07/2023] [Indexed: 04/12/2024]
Abstract
Coagulation management in the patient with cirrhosis has undergone a significant transformation since the beginning of this century, with the concept of a rebalancing between procoagulant and anticoagulant factors. The paradigm that patients with cirrhosis have a greater bleeding tendency has changed, as a result of this rebalancing. In addition, it has brought to light the presence of complications related to thrombotic events in this group of patients. These guidelines detail aspects related to pathophysiologic mechanisms that intervene in the maintenance of hemostasis in the patient with cirrhosis, the relevance of portal hypertension, mechanical factors for the development of bleeding, modifications in the hepatic synthesis of coagulation factors, and the changes in the reticuloendothelial system in acute hepatic decompensation and acute-on-chronic liver failure. They address new aspects related to the hemorrhagic complications in patients with cirrhosis, considering the risk for bleeding during diagnostic or therapeutic procedures, as well as the usefulness of different tools for diagnosing coagulation and recommendations on the pharmacologic treatment and blood-product transfusion in the context of hemorrhage. These guidelines also update the knowledge regarding hypercoagulability in the patient with cirrhosis, as well as the efficacy and safety of treatment with the different anticoagulation regimens. Lastly, they provide recommendations on coagulation management in the context of acute-on-chronic liver failure, acute liver decompensation, and specific aspects related to the patient undergoing liver transplantation.
Collapse
Affiliation(s)
- I Aiza-Haddad
- Clínica de Enfermedades Hepáticas, Hospital Ángeles Lomas, Mexico City, Mexico.
| | - L E Cisneros-Garza
- Departamento de Gastroenterología y Hepatología, Hospital Christus Muguerza Alta Especialidad, Monterrey, Mexico
| | - O Morales-Gutiérrez
- Departamento de Gastroenterología y Hepatología, Hospital General de México «Dr. Eduardo Liceaga», Mexico City, Mexico
| | | | - M T Rizo-Robles
- Departamento de Gastroenterología y Hepatología, Instituto Mexicano del Seguro Social Centro Médico Nacional «La Raza», Mexico City, Mexico
| | - R Alvarado-Reyes
- Departamento de Hepatología, Hospital San José Tec Salud, Monterrey, Mexico
| | | | | | - E Cerda-Reyes
- Servicio de Gastroenterología, Hospital Central Militar, Mexico City, Mexico
| | - R Contreras-Omaña
- Centro de Investigación en Enfermedades Hepáticas y Gastroenterología (CIEHG) Pachuca, Hidalgo, México
| | | | - N C Flores-García
- Escuela de Medicina y Ciencias de la Salud. Tecnológico de Monterrey, Monterrey Nuevo Leon, México
| | | | - M F Higuera-de la Tijera
- Departamento de Gastroenterología y Hepatología, Hospital General de México «Dr. Eduardo Liceaga», Mexico City, Mexico
| | - M A Lira-Pedrin
- Departamento de Gastroenterología, Endoscopía Digestiva, Motilidad y Hepatología, Centro Médico Corporativo Galeana, Tijuana, México
| | - J E Lira-Vera
- Departamento de Gastroenterología y Hepatología, Hospital General de México «Dr. Eduardo Liceaga», Mexico City, Mexico
| | | | - D E Meléndez-Mena
- Hospital General de Especialidades «Maximino Ávila Camacho», IMSS, UMAE, Puebla, México
| | - M R Muñoz-Ramírez
- Departamento de Hepatología, Hospital San José Tec Salud, Monterrey, Mexico
| | - J L Pérez-Hernández
- Departamento de Gastroenterología y Hepatología, Hospital General de México «Dr. Eduardo Liceaga», Mexico City, Mexico
| | - M V Ramos-Gómez
- Departamento Hepatología, ISSSTE, Centro Médico Nacional «20 de noviembre», Ciudad de México, México
| | - J F Sánchez-Ávila
- Escuela de Medicina y Ciencias de la Salud. Tecnológico de Monterrey, Monterrey Nuevo Leon, México
| |
Collapse
|
|
10
|
Wan Y, Guo L, Xiong M. Effect of Direct Oral Anticoagulants in Patients with Splanchnic Vein Thrombosis: A Systematic Reviews and Meta-Analysis. Clin Appl Thromb Hemost 2024; 30:10760296241274750. [PMID: 39135448 PMCID: PMC11322924 DOI: 10.1177/10760296241274750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 07/16/2024] [Accepted: 07/25/2024] [Indexed: 08/16/2024] Open
Abstract
BACKGROUND Since several studies have examined the use of direct oral anticoagulants (DOACs) in treating patients with splanchnic vein thrombosis (SVT), we conducted a meta-analyses to assess the safety and efficacy of DOACs compared to vitamin K antagonists (VKAs) in this population. METHODS We conducted a comprehensive search using the PubMed, Embase, and Cochrane Library databases until June 2024. We used odds ratios (ORs) and 95% confidence intervals (CIs) as the effect measures to compare DOACs with VKAs. RESULTS A total of 9 observational studies were included. The pooled analysis revealed that a trend towards higher complete recanalization rates with DOACs (71.4%) compared to VKAs (55.3%), though not statistically significant (OR 1.95; 95%CI 0.70 to 5.44). For SVT extension, a significant effect was observed favoring DOACs (OR 0.12; 95%CI 0.03 to 0.54). No significant differences were found in other efficacy outcomes or safety outcomes, except for major bleeding, which was significantly lower with DOACs (OR 0.27; 95%CI 0.13 to 0.56). CONCLUSION DOACs are superior to VKAs in SVT extension and major bleeding, suggesting that DOACs may be a favorable treatment option in the treatment of SVT.
Collapse
Affiliation(s)
- Yun Wan
- Department of Gastroenterology, Ganzhou People's Hospital, Ganzhou, China
| | - Linjuan Guo
- Department of Cardiology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, China
| | - Meimei Xiong
- Department of Nephrology, the First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
| |
Collapse
|
|
11
|
Ghazaleh S, Chuang J, Sayeh W, Iqbal A, Beran A, Khader Y, Burmeister C, Aziz M, Assaly R, Nawras A. Comparative Efficacy of Anticoagulant Medications in Nonmalignant Portal Vein Thrombosis in Liver Cirrhosis-A Systematic Review and Network Meta-analysis. Am J Ther 2023; 30:e591-e594. [PMID: 36927678 DOI: 10.1097/mjt.0000000000001538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/18/2023]
Affiliation(s)
- Sami Ghazaleh
- Department of Internal Medicine, University of Toledo, Toledo, OH
| | - Justin Chuang
- Department of Internal Medicine, University of Toledo, Toledo, OH
| | - Wasef Sayeh
- Department of Internal Medicine, University of Toledo, Toledo, OH
| | - Amna Iqbal
- Department of Internal Medicine, University of Toledo, Toledo, OH
| | - Azizullah Beran
- Department of Internal Medicine, University of Toledo, Toledo, OH
| | - Yasmin Khader
- Department of Internal Medicine, University of Toledo, Toledo, OH
| | | | - Muhammad Aziz
- Division of Gastroenterology and Hepatology, University of Toledo, Toledo, OH
| | - Ragheb Assaly
- Department of Internal Medicine, University of Toledo, Toledo, OH
| | - Ali Nawras
- Division of Gastroenterology and Hepatology, University of Toledo, Toledo, OH
| |
Collapse
|
|
12
|
Li Z, Xu W, Wang L, Chai L, Ageno W, Romeiro FG, Li H, Qi X. Risk of Bleeding in Liver Cirrhosis Receiving Direct Oral Anticoagulants: A Systematic Review and Meta-analysis. Thromb Haemost 2023; 123:1072-1088. [PMID: 37336474 DOI: 10.1055/s-0043-1770100] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/21/2023]
Abstract
BACKGROUND Direct oral anticoagulants (DOACs) are effective for the management of thromboembolic disorders. However, bleeding remains a major concern in cirrhotic patients receiving DOACs. METHODS PubMed, EMBASE, and Cochrane Library databases were searched. The incidence of bleeding episodes in cirrhotic patients receiving DOACs was pooled. Odds ratios (ORs) were calculated to compare the incidence of bleeding episodes in cirrhotic patients who received DOACs versus those who received conventional anticoagulants and did not receive anticoagulants. RESULTS Twenty-nine studies were included. All bleeding, major bleeding, fatal bleeding, gastrointestinal bleeding, and intracranial hemorrhage episodes were observed in 310/2,469, 100/1,388, 2/611, 166/1,886, and 5/1,147 cirrhotic patients receiving DOACs, respectively. Their pooled incidences were 13, 6, 0, 8, and 0%, respectively. They became higher in subgroup analyses of studies with advanced age, a longer treatment duration, and Child-Turcotte-Pugh class C. Compared with conventional anticoagulants, DOACs were associated with lower incidences of all bleeding (OR = 0.71, 95% confidence interval [CI] = 0.52-0.98) and major bleeding (OR = 0.55, 95% CI = 0.37-0.83) in cirrhotic patients, but not those of fatal bleeding (OR = 0.21, 95% CI = 0.04-1.28), gastrointestinal bleeding (OR = 0.78, 95% CI = 0.52-1.17), or intracranial hemorrhage (OR = 0.36, 95% CI = 0.12-1.12). The incidences of all bleeding (OR = 1.04, 95% CI = 0.22-4.79) and major bleeding (OR = 0.96, 95% CI = 0.26-3.61) did not significantly differ between cirrhotic patients with portal vein thrombosis (PVT) who received DOACs and those who did not receive anticoagulants. CONCLUSION DOACs carry a low risk of bleeding in liver cirrhosis. Age, treatment duration, and Child-Turcotte-Pugh class may be associated with bleeding in cirrhotic patients receiving DOACs. The risk of bleeding is not increased by DOACs in cirrhotic patients with PVT.
Collapse
Affiliation(s)
- Zhe Li
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - Wentao Xu
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - Le Wang
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Postgraduate College, China Medical University, Shenyang, China
| | - Lu Chai
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - Walter Ageno
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Fernando Gomes Romeiro
- Department of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), São Paulo, Brazil
| | - Hongyu Li
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
- Postgraduate College, China Medical University, Shenyang, China
| | - Xingshun Qi
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
- Postgraduate College, China Medical University, Shenyang, China
| |
Collapse
|
|
13
|
Swan D, Lisman T, Tripodi A, Thachil J. The prothrombotic tendency of metabolic-associated fatty liver disease. J Thromb Haemost 2023; 21:3045-3055. [PMID: 37353082 DOI: 10.1016/j.jtha.2023.06.017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 05/12/2023] [Accepted: 06/12/2023] [Indexed: 06/25/2023]
Abstract
Our understanding of the function of the liver has evolved over the centuries. Early theories proposing that the liver could be used to divine the future have been superseded by our current knowledge of the importance of the liver in processes such as digestion and detoxification. Similarly, although liver disease was previously associated with only an increased risk of bleeding, there is now a substantial body of evidence demonstrating an increased thrombotic potential in patients with this disease. Metabolic-associated fatty liver disease (MAFLD) is increasing in frequency and is likely to overtake alcoholic liver disease as the primary indication for liver transplant in the future. In this review, we discuss the evidence linking liver disease, and MAFLD in particular, with arterial and venous thromboembolic disease. We review the safety and efficacy of anticoagulation in advanced liver disease and consider whether antithrombotic agents could slow or halt the progression of fibrosis in MAFLD.
Collapse
Affiliation(s)
- Dawn Swan
- Department of Haematology, Beaumont Hospital, Dublin, Ireland.
| | - Ton Lisman
- Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Armando Tripodi
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione Luigi Villa, Milano, Italy
| | - Jecko Thachil
- Department of Haematology, Manchester University Hospitals, Oxford Road, Manchester, UK
| |
Collapse
|
|
14
|
Monaco G, Bucherini L, Stefanini B, Piscaglia F, Foschi FG, Ielasi L. Direct oral anticoagulants for the treatment of splanchnic vein thrombosis: A state of art. World J Gastroenterol 2023; 29:4962-4974. [PMID: 37731994 PMCID: PMC10507502 DOI: 10.3748/wjg.v29.i33.4962] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 08/07/2023] [Accepted: 08/17/2023] [Indexed: 09/01/2023] Open
Abstract
Splanchnic vein thrombosis (SVT) is a manifestation of venous thromboembolism in an unusual site. Portal, mesenteric, and splenic veins are the most common vessels involved in SVT which occurs mainly in patients with liver cirrhosis, although non-cirrhotic patients could be affected as well. Thrombosis of hepatic veins, also known as Budd-Chiari syndrome, is another manifestation of SVT. Prompt diagnosis and intervention are mandatory in order to increase the recalization rate and reduce the risk of thrombus progression and hypertensive complications. Traditional anticoagulation with heparin and vitamin-K antagonists is the treatment of choice in these cases. However, recent studies have shown promising results on the efficacy and safety of direct oral anticoagulants (DOACs) in this setting. Available results are mainly based on retrospective studies with small sample size, but first clinical trials have been published in the last years. This manuscript aims to provide an updated overview of the current evidence regarding the role of DOACs for SVT in both cirrhotic and non-cirrhotic patients.
Collapse
Affiliation(s)
- Giovanni Monaco
- Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Luca Bucherini
- Department of Internal Medicine, Ospedale degli Infermi di Faenza, Faenza 48018, Italy
| | - Bernardo Stefanini
- Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Fabio Piscaglia
- Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | | | - Luca Ielasi
- Department of Internal Medicine, Ospedale degli Infermi di Faenza, Faenza 48018, Italy
| |
Collapse
|
|
15
|
Li A, Zhang MC, Li P, Eshaghpour A, Li K, Carrier M, Wells P, Crowther MA. Direct oral anticoagulants for the treatment of splanchnic vein thrombosis - A systematic review and meta-analysis. Thromb Res 2023; 229:209-218. [PMID: 37544136 DOI: 10.1016/j.thromres.2023.06.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Revised: 05/10/2023] [Accepted: 06/02/2023] [Indexed: 08/08/2023]
Abstract
BACKGROUND Splanchnic vein thrombosis (SVT) is an uncommon manifestation of venous thromboembolism in the splanchnic venous system, with scarce evidence surrounding its management. We assessed the efficacy and safety of direct oral anticoagulant (DOAC) to low-molecular-weight heparins (LMWH), vitamin-k antagonists (VKAs), or no anticoagulation. METHODS We conducted a systematic review and meta-analysis with the primary efficacy outcome being complete recanalization of affected vessels and primary safety outcome being major bleeding. Meta-analysis was done using a random-effects model, with dichotomous outcomes being synthesized with odds ratios (ORs) and corresponding 95 % CIs. RESULTS Seven non-randomized and one randomized study involving 883 participants were included for analysis. DOACs were more effective than VKAs (OR = 4.33; 95 % CI: 2.4, 7.83; n = 1 study) in non-cirrhotic patients and no anticoagulation in cirrhotic patients (OR = 3.86; 95 % CI: 1.49, 10.03; n = 3 studies). DOACs had a statistically significant reduction in major bleeding compared to observation [OR = 0.09; 95 % CI: 0.03, 0.29; n = 3 studies], LMWHs [OR = 0.13; 95 % CI: 0.03, 0.29; n = 1 study] and VKAs [OR = 0.12; 95 % CI: 0.02, 0.69; n = 2 studies] in non-cirrhotic patients. No difference in major bleeding was found between DOACs and observation, LMWH, or VKAs in cirrhotic patients. CONCLUSION DOACs appear to be a favorable alternative to VKAs and LMWHs in non-cirrhotic patients. This avenue of research would benefit from larger studies that adjust for SVT etiologies, patient risk factors, and overall bleeding risk.
Collapse
Affiliation(s)
- Allen Li
- The Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, Ontario, Canada; Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
| | - Ming Chan Zhang
- Michael G. DeGroote School of Medicine, Hamilton, Ontario, Canada
| | - Pei Li
- Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Ali Eshaghpour
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Katherine Li
- The Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, Ontario, Canada; Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Marc Carrier
- The Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, Ontario, Canada; Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Philip Wells
- The Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, Ontario, Canada; Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | | |
Collapse
|
|
16
|
Cohen O, Efros O, Riva N, Ageno W, Soffer S, Klang E, Barg AA, Kenet G, Levy-Mendelovich S. Anticoagulant treatment for pediatric splanchnic vein thrombosis: a systematic review and meta-analysis. J Thromb Haemost 2023; 21:2499-2508. [PMID: 37225019 DOI: 10.1016/j.jtha.2023.05.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 04/29/2023] [Accepted: 05/10/2023] [Indexed: 05/26/2023]
Abstract
BACKGROUND The clinical characteristics of splanchnic vein thrombosis (SVT) in pediatric patients and its optimal treatment strategies are unknown. OBJECTIVES This study aimed to assess the effectiveness and safety of anticoagulant therapy for pediatric SVT. METHODS MEDLINE and EMBASE databases were searched up to December 2021. We included observational and interventional studies that enrolled pediatric patients with SVT and reported anticoagulant treatment and outcomes, including rates of vessel recanalization, SVT extension, venous thromboembolism (VTE) recurrence, major bleeding, and mortality. Pooled proportions of vessel recanalization were calculated with their 95% CI. RESULTS A total of 506 pediatric patients (aged 0-18 years) across 17 observational studies were included. The majority of patients had portal vein thrombosis (n = 308, 60.8%) or Budd-Chiari syndrome (n = 175, 34.6%). Most events were triggered by transient provoking factors. Anticoagulation (heparins and vitamin K antagonists) was prescribed in 217 (42.9%) patients, and 148 (29.2%) patients underwent vascular interventions. The overall pooled proportions of vessel recanalization were 55.3% (95% CI, 34.1%-74.7%; I2 = 74.0%) among anticoagulated patients and 29.4% (95% CI, 2.6%-86.6%; I2 = 49.0%) among non-anticoagulated patients. SVT extension, major bleeding, VTE recurrence, and mortality rates were 8.9%, 3.8%, 3.5%, and 10.0%, respectively, in anticoagulated patients and 2.8%, 1.4%, 0%, and 50.3%, respectively, in non-anticoagulated patients. CONCLUSION In pediatric SVT, anticoagulation appears to be associated with moderate recanalization rates and a low risk of major bleeding. VTE recurrence is low and comparable to that reported in pediatric patients with other types of provoked VTE.
Collapse
Affiliation(s)
- Omri Cohen
- National Hemophilia Center, Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel-Hashomer, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Orly Efros
- National Hemophilia Center, Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel-Hashomer, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Nicoletta Riva
- Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
| | - Walter Ageno
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Shelly Soffer
- Internal Medicine B, Assuta Medical Center, Ashdod, Israel; Ben-Gurion University of the Negev, Be'er Sheva, Israel
| | - Eyal Klang
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Diagnostic Imaging, Sheba Medical Center, Tel-Hashomer, Israel; Sheba Talpiot Medical Leadership Program, Sheba Medical Center, Tel-Hashomer, Israel
| | - Assaf A Barg
- National Hemophilia Center, Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel-Hashomer, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Gili Kenet
- National Hemophilia Center, Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel-Hashomer, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Sarina Levy-Mendelovich
- National Hemophilia Center, Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel-Hashomer, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Sheba Talpiot Medical Leadership Program, Sheba Medical Center, Tel-Hashomer, Israel.
| |
Collapse
|
|
17
|
Choi MJ, Woo MR, Baek K, Park JH, Joung S, Choi YS, Choi HG, Jin SG. Enhanced Oral Bioavailability of Rivaroxaban-Loaded Microspheres by Optimizing the Polymer and Surfactant Based on Molecular Interaction Mechanisms. Mol Pharm 2023; 20:4153-4164. [PMID: 37433746 DOI: 10.1021/acs.molpharmaceut.3c00281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/13/2023]
Abstract
This study aimed to develop microspheres using water-soluble carriers and surfactants to improve the solubility, dissolution, and oral bioavailability of rivaroxaban (RXB). RXB-loaded microspheres with optimal carrier (poly(vinylpyrrolidone) K30, PVP) and surfactant (sodium lauryl sulfate (SLS)) ratios were prepared. 1H NMR and Fourier transform infrared (FTIR) analyses showed that drug-excipient and excipient-excipient interactions affected RXB solubility, dissolution, and oral absorption. Therefore, molecular interactions between RXB, PVP, and SLS played an important role in improving RXB solubility, dissolution, and oral bioavailability. Formulations IV and VIII, containing optimized RXB/PVP/SLS ratios (1:0.25:2 and 1:1:2, w/w/w), had significantly improved solubility by approximately 160- and 86-fold, respectively, compared to RXB powder, with the final dissolution rates improved by approximately 4.5- and 3.4-fold, respectively, compared to those of RXB powder at 120 min. Moreover, the oral bioavailability of RXB was improved by 2.4- and 1.7-fold, respectively, compared to that of RXB powder. Formulation IV showed the highest improvement in oral bioavailability compared to RXB powder (AUC, 2400.8 ± 237.1 vs 1002.0 ± 82.3 h·ng/mL). Finally, the microspheres developed in this study successfully improved the solubility, dissolution rate, and bioavailability of RXB, suggesting that formulation optimization with the optimal drug-to-excipient ratio can lead to successful formulation development.
Collapse
Affiliation(s)
- Min-Jong Choi
- Department of Pharmaceutical Engineering, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan 31116, South Korea
| | - Mi Ran Woo
- College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 15588, South Korea
| | - Kyungho Baek
- Department of Pharmaceutical Engineering, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan 31116, South Korea
| | - Ji Hun Park
- Department of Science Education, Ewha Womans University, Seoul 03760, South Korea
| | - Seewon Joung
- Department of Chemistry, Inha University, Incheon 22212, South Korea
| | - Yong Seok Choi
- College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan 31116, South Korea
| | - Han-Gon Choi
- College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 15588, South Korea
| | - Sung Giu Jin
- Department of Pharmaceutical Engineering, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan 31116, South Korea
| |
Collapse
|
|
18
|
Wu Z, Xiao Y, Wang Y. Portal vein thrombosis in liver cirrhosis: An updated overview. PORTAL HYPERTENSION & CIRRHOSIS 2023; 2:78-91. [DOI: 10.1002/poh2.46] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Accepted: 04/11/2023] [Indexed: 01/03/2025]
Abstract
AbstractPortal vein thrombosis (PVT) is a frequent and severe complication in patients with cirrhosis; however, the pathophysiology of PVT needs to be better clarified. There are few significant predictive factors in clinical practice, and the impact of PVT on cirrhosis progression and its complications, such as gastrointestinal bleeding, hepatic encephalopathy, and hepatorenal syndrome, remains uncertain. In recent years, the understanding of the mechanisms of PVT has become more profound with the publication of related literature. Therefore, in this review, we aim to summarize the advanced progress in the epidemiology, hazards, risk factors, diagnosis and classification, and treatment of PVT to provide insight into clinical management.
Collapse
Affiliation(s)
- Zhinian Wu
- Department of Infectious Diseases The Third Affiliated Hospital of Hebei Medical University Shijiazhuang Hebei China
| | - Ying Xiao
- Department of Infectious Diseases The Third Affiliated Hospital of Hebei Medical University Shijiazhuang Hebei China
| | - Yadong Wang
- Department of Infectious Diseases The Third Affiliated Hospital of Hebei Medical University Shijiazhuang Hebei China
| |
Collapse
|
|
19
|
Protopapas AA, Savopoulos C, Skoura L, Goulis I. Anticoagulation in Patients with Liver Cirrhosis: Friend or Foe? Dig Dis Sci 2023; 68:2237-2246. [PMID: 36961672 PMCID: PMC10188576 DOI: 10.1007/s10620-023-07858-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 01/28/2023] [Indexed: 03/25/2023]
Abstract
Concepts regarding the status of the coagulation process in cirrhosis are rapidly changing. Instead of a disease defined by excessive bleeding risk, recent studies have shown cirrhosis to be associated with a fragile state of rebalanced hemostasis, easily swayed in either direction, thrombosis, or bleeding. These findings, combined with the ever-growing population of patients with cirrhosis with an indication for anticoagulation (AC) and the emergence of the non-alcoholic fatty liver disease epidemic, have prompted a reexamination of the use of AC in patients with cirrhosis, either as a treatment for a concurrent thrombotic disorder or even as a possible therapeutic option that could influence the natural course of the disease and its complications. In recent years, a significant number of studies have been formulated to evaluate these possibilities. These studies evaluated, among others, the efficacy and safety of AC in thrombotic disorders or thrombotic complications of cirrhosis, its effect on survival, and the class of anticoagulants which is more suitable for patients with cirrhosis, depending on disease severity. This review examines recent studies investigating the use of AC in patients with cirrhosis and attempts to provide a simple guide for clinicians regarding the use of AC in patients with cirrhosis and its potential risks and benefits.
Collapse
Affiliation(s)
- Adonis A Protopapas
- First Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636, Thessaloniki, Greece.
| | - Christos Savopoulos
- First Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636, Thessaloniki, Greece
| | - Lemonia Skoura
- Department of Microbiology, Aristotle University οf Thessaloniki, AHEPA University Hospital, 54636, Thessaloniki, Greece
| | - Ioannis Goulis
- Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration Hospital, 54642, Thessaloniki, Greece
| |
Collapse
|
|
20
|
Elkrief L, Payancé A, Plessier A, d’Alteroche L, Ronot M, Paradis V, Valla D, Rautou PE. Management of splanchnic vein thrombosis. JHEP Rep 2023; 5:100667. [PMID: 36941824 PMCID: PMC10023986 DOI: 10.1016/j.jhepr.2022.100667] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 12/11/2022] [Accepted: 12/23/2022] [Indexed: 01/04/2023] Open
Abstract
The expression splanchnic vein thrombosis encompasses Budd-Chiari syndrome and portal vein thrombosis. These disorders have common characteristics: they are both rare diseases which can cause portal hypertension and its complications. Budd-Chiari syndrome and portal vein thrombosis in the absence of underlying liver disease share many risk factors, among which myeloproliferative neoplasms represent the most common; a rapid comprehensive work-up for risk factors of thrombosis is needed in these patients. Long-term anticoagulation is indicated in most patients. Portal vein thrombosis can also develop in patients with cirrhosis and in those with porto-sinusoidal vascular liver disease. The presence and nature of underlying liver disease impacts the management of portal vein thrombosis. Indications for anticoagulation in patients with cirrhosis are growing, while transjugular intrahepatic portosystemic shunt is now a second-line option. Due to the rarity of these diseases, studies yielding high-grade evidence are scarce. However, collaborative studies have provided new insight into the management of these patients. This article focuses on the causes, diagnosis, and management of patients with Budd-Chiari syndrome, portal vein thrombosis without underlying liver disease, or cirrhosis with non-malignant portal vein thrombosis.
Collapse
Key Words
- BCS, Budd-Chiari syndrome
- CALR, calreticulin
- Cavernoma
- DOACs, direct-acting oral anticoagulants
- Direct oral anticoagulants
- EHPVO, extrahepatic portal vein obstruction
- GFR, glomerular filtration rate
- JAK2, Janus kinase 2
- LMWH, low-molecular-weight heparin
- MPN, myeloproliferative neoplasm
- MTHFR, methylene-tetrahydrofolate reductase
- PNH, paroxysmal nocturnal hemoglobinuria
- PVT, portal vein thrombosis
- Portal biliopathy
- Portal vein recanalisation
- SVT, splanchnic vein thrombosis
- TIPS, transjugular intrahepatic portosystemic shunt
- VKAs, vitamin K antagonists
- Vascular liver diseases
Collapse
Affiliation(s)
- Laure Elkrief
- Service d’Hépato-Gastroentérologie CHU de Tours, France
| | - Audrey Payancé
- Université Paris-Cité, Inserm, Centre de recherche sur l'inflammation, UMR 1149, Paris, France
- Service d'Hépatologie, AP-HP, Hôpital Beaujon, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France
| | - Aurélie Plessier
- Université Paris-Cité, Inserm, Centre de recherche sur l'inflammation, UMR 1149, Paris, France
- Service d'Hépatologie, AP-HP, Hôpital Beaujon, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France
| | | | - Maxime Ronot
- Université Paris-Cité, Inserm, Centre de recherche sur l'inflammation, UMR 1149, Paris, France
- Service de radiologie, Hôpital Beaujon APHP.Nord, Clichy, France
| | - Valérie Paradis
- Université Paris-Cité, Inserm, Centre de recherche sur l'inflammation, UMR 1149, Paris, France
- Service d’anatomie et cytologie pathologique, Hôpital Beaujon APHP.Nord, Clichy, France
| | - Dominique Valla
- Université Paris-Cité, Inserm, Centre de recherche sur l'inflammation, UMR 1149, Paris, France
- Service d'Hépatologie, AP-HP, Hôpital Beaujon, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France
| | - Pierre-Emmanuel Rautou
- Université Paris-Cité, Inserm, Centre de recherche sur l'inflammation, UMR 1149, Paris, France
- Service d'Hépatologie, AP-HP, Hôpital Beaujon, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France
| |
Collapse
|
|
21
|
Oktaviana J, Lui B, Ho P, Lim HY. A 10-year Australian experience of rare intraabdominal venous thrombosis with comparison to deep vein thrombosis and pulmonary embolism. Blood Coagul Fibrinolysis 2023; 34:191-198. [PMID: 36966765 DOI: 10.1097/mbc.0000000000001213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/28/2023]
Abstract
OBJECTIVE Intra-abdominal venous thromboembolism is rare with heterogeneous management. We aim to evaluate these thrombosis and compare them to deep vein thrombosis and/or pulmonary embolism. METHOD A 10-year retrospective evaluation of consecutive venous thromboembolism presentations (January 2011-December 2020) at Northern Health, Australia, was conducted. A subanalysis of intraabdominal venous thrombosis involving splanchnic, renal and ovarian veins was performed. RESULTS There were 3343 episodes including 113 cases of intraabdominal venous thrombosis (3.4%) - 99 splanchnic vein thrombosis, 10 renal vein thrombosis and 4 ovarian vein thrombosis. Of the splanchnic vein thrombosis presentations, 34 patients (35 cases) had known cirrhosis. Patients with cirrhosis were numerically less likely to be anticoagulated compared to noncirrhotic patients (21/35 vs. 47/64, P = 0.17). Noncirrhotic patients ( n = 64) were more likely to have malignancy compared to those with deep vein thrombosis and/or pulmonary embolism (24/64 vs. 543/3230, P < 0.001), including 10 patients diagnosed at time of splanchnic vein thrombosis presentation. Cirrhotic patients reported more recurrent thrombosis/clot progression (6/34) compared to noncirrhotic patients (3/64) (15.6 vs. 2.3 events/100-person-years; hazard ratio 4.7 (95% confidence interval 1.2-18.9), P = 0.030) and other venous thromboembolism patients (2.6/100-person-years; hazard ratio 4.7, 95% confidence interval 2.1-10.7; P < 0.001) with comparable major bleeding rates. All renal vein thrombosis were provoked including five malignant-related cases while three ovarian vein thrombosis occurred postpartum. No recurrent thrombotic or bleeding complications were reported in renal vein thrombosis and ovarian vein thrombosis. CONCLUSION These rare intraabdominal venous thromboses are often provoked. Splanchnic vein thrombosis (SVT) patients with cirrhosis have a higher rate of thrombotic complications, while SVT without cirrhosis was associated with more malignancy. Given the concurrent comorbidities, careful assessment and individualized anticoagulation decision is needed.
Collapse
Affiliation(s)
- Jesica Oktaviana
- Northern Clinical Pathology, Thrombosis and Radiology (NECTAR) Research Group (Northern Pathology Victoria), Department of Haematology, Northern Health, Epping
| | - Brandon Lui
- Northern Clinical Pathology, Thrombosis and Radiology (NECTAR) Research Group (Northern Pathology Victoria), Department of Haematology, Northern Health, Epping
| | - Prahlad Ho
- Northern Clinical Pathology, Thrombosis and Radiology (NECTAR) Research Group (Northern Pathology Victoria), Department of Haematology, Northern Health, Epping
- Australian Centre for Blood Diseases, Monash University, Melbourne
- Department of Medicine (Northern Health), University of Melbourne, Heidelberg, VIC, Australia
| | - Hui Y Lim
- Northern Clinical Pathology, Thrombosis and Radiology (NECTAR) Research Group (Northern Pathology Victoria), Department of Haematology, Northern Health, Epping
- Australian Centre for Blood Diseases, Monash University, Melbourne
- Department of Medicine (Northern Health), University of Melbourne, Heidelberg, VIC, Australia
| |
Collapse
|
|
22
|
Benevento F, Pecorelli A, Stefanescu H, Sparchez Z, Vukotic R, Pettinari I, Grigoras CA, Tovoli F, Ravaioli F, Stefanini B, Andreone P, Piscaglia F. Presence of Hepatocellular Carcinoma Does Not Affect Course and Response to Anticoagulation of Bland Portal Vein Thrombosis in Cirrhotic Patients. J Hepatocell Carcinoma 2023; 10:473-482. [PMID: 37007210 PMCID: PMC10065221 DOI: 10.2147/jhc.s390777] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 03/15/2023] [Indexed: 03/29/2023] Open
Abstract
BACKGROUND Malignancies are generally considered a risk factor for deep vein thrombosis and may hamper the recanalisation of thrombosed veins. AIM We investigate whether the natural course and response to anticoagulant treatment of bland portal vein thrombosis (PVT) in patients with cirrhosis complicated by hepatocellular carcinoma (HCC) differ from those without HCC. METHODS Retrospective study in two hepatology referral centres, in Italy and Romania where patients with a diagnosis of PVT on cirrhosis and follow-up of at least 3 months with repeated imaging were included. RESULTS A total of 162 patients with PVT and matching inclusion and exclusion criteria were identified: 30 with HCC were compared to 132 without HCC. Etiologies, Child-Pugh Score (7 vs 7) and MELD scores (11 vs 12, p=0.3679) did not differ. Anticoagulation was administered to 43% HCC vs 42% nonHCC. The extension of PVT in the main portal trunk was similar: partial/total involvement was 73.3/6.7% in HCC vs 67.4/6.1% in nonHCC, p=0.760. The remainder had intrahepatic PVT. The recanalization rate was 61.5% and 60.7% in HCC/nonHCC in anticoagulated patients (p=1). Overall PVT recanalisation, including treated and untreated patients, was observed in 30% of HCC vs 37.9% of nonHCC, p=0.530. Major bleeding incidence was almost identical (3.3% vs 3.8%, p=1). Progression of PVT after stopping anticoagulation did not differ (10% vs 15.9%, respectively, HCC/nHCC, p=0.109). CONCLUSION The course of bland non-malignant PVT in cirrhosis is not affected by the presence of active HCC. Treatment with anticoagulation in patients with active HCC is safe and as effective as in nonHCC patients, this can potentially allow us to use otherwise contraindicated therapies (ie TACE) if a complete recanalization is achieved with anticoagulation.
Collapse
Affiliation(s)
- Francesca Benevento
- Department of Medicine and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Anna Pecorelli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Horia Stefanescu
- Gastroenterology Department, Liver Unit & Ultrasound Laboratory, Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania
| | - Zeno Sparchez
- Gastroenterology Department, Liver Unit & Ultrasound Laboratory, Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania
| | - Ranka Vukotic
- Department of Medicine and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
- Medicina Interna 4, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Irene Pettinari
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Crina-Anca Grigoras
- Gastroenterology Department, Liver Unit & Ultrasound Laboratory, Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania
| | - Francesco Tovoli
- Department of Medicine and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Federico Ravaioli
- Department of Medicine and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Bernardo Stefanini
- Department of Medicine and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Pietro Andreone
- Divisione di Medicina Interna a Indirizzo Metabolico-Nutrizionale, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
| | - Fabio Piscaglia
- Department of Medicine and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| |
Collapse
|
|
23
|
Wang SM, Wen J, Hu L, Wu LP, Yuan DQ. Rivaroxaban combined with repeat hepatectomy for treatment of cirrhosis-related acute portal vein thrombosis with hepatocellular carcinoma: A case report. Shijie Huaren Xiaohua Zazhi 2023; 31:201-206. [DOI: 10.11569/wcjd.v31.i5.201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/08/2023] Open
Abstract
BACKGROUND Acute portal vein thrombosis (PVT) with hepatocellular carcinoma (HCC) is a severe complication of liver cirrhosis and its prognosis is affected by clinical decision to a large extent, while the order of management, the approaches of treatment, and the adjustment of the plan are all the key and difficult points.
CASE SUMMARY This case was treated with low molecular weight heparin (4000 U/12 h) for 14 d, followed by rivaroxaban (10 mg/12 h) and then partial hepatectomy twice, of which the first was performed 1 mo after anticoagulation, and the second was performed 4 mo later, by which the primary lesion and postoperative new lesion were resected, respectively. Rivaroxaban was taken constantly except the perioperative period, while gingival bleeding occurred after 8 mo of anticoagulation, so suspension of rivaroxaban was carried out for 1 wk, after which the bleeding was relieved, and a half dose of rivaroxaban (10 mg/d) was used to continue anticoagulation from then on. The thrombus remained recanalized and there was no tumor recurrence during the following 2 years.
CONCLUSION When there are indications for anticoagulation and partial hepatectomy in patients with cirrhosis-related acute PVT with HCC, anticoagulation followed by surgery is recommended, as anticoagulation may reduce thrombosis in a short time, which could not only decrease the risk of surgery, but also have little influence on the opportunity of tumor treatment. And when recurrence of HCC occurs, if possible, repeat hepatectomy should be considered to improve the prognosis. Anticoagulant strategy should be adjusted accordingly if rivaroxaban causes bleeding, and it should be stopped or reduced after the bleeding is stable.
Collapse
Affiliation(s)
- Shi-Mei Wang
- Department of Gastroenterology, The Third People's Hospital of Chengdu and Affiliated Hospital of Southwest Jiaotong University, Chengdu 610031, Sichuan Province, China
| | - Jun Wen
- Department of General Surgery, The Third People's Hospital of Chengdu and Affiliated Hospital of Southwest Jiaotong University, Chengdu 610031, Sichuan Province, China
| | - Ling Hu
- Department of Gastroenterology, The Third People's Hospital of Chengdu and Affiliated Hospital of Southwest Jiaotong University, Chengdu 610031, Sichuan Province, China
| | - Li-Ping Wu
- Department of Gastroenterology, The Third People's Hospital of Chengdu and Affiliated Hospital of Southwest Jiaotong University, Chengdu 610031, Sichuan Province, China
| | - De-Qiang Yuan
- Department of Gastroenterology, The Third People's Hospital of Chengdu and Affiliated Hospital of Southwest Jiaotong University, Chengdu 610031, Sichuan Province, China
| |
Collapse
|
|
24
|
Gao Z, Li S, Zhao J, Li J, Gao Y. Anticoagulation therapy early is safe in portal vein thrombosis patients with acute variceal bleeding: a multi-centric randomized controlled trial. Intern Emerg Med 2023; 18:513-521. [PMID: 36692588 DOI: 10.1007/s11739-023-03206-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Accepted: 01/10/2023] [Indexed: 01/25/2023]
Abstract
Portal vein thrombosis (PVT) and acute variceal bleeding (AVB) are frequent complications of cirrhosis. The efficacy, safety, and timing of anticoagulant treatment in cirrhotic patients with PVT and AVB are contentious issues. We aimed to establish the safety and efficacy of initiating nadroparin calcium-warfarin sequential (NWS) anticoagulation therapy early after esophageal variceal band ligation within PVT patients having cirrhosis and AVB. Cirrhotic patients having AVB and PVT who underwent EVL were included and randomly allocated to either the NWS therapy group (1-month nadroparin calcium by subcutaneous injection following 5-month warfarin through oral administration, n = 43) or the control group (without any anticoagulation therapy, n = 43). The primary endpoint was the rate of PVT recanalization. Secondary endpoints included major bleeding events mainly referring to variceal rebleeding (5-day failure, 14-day, 4-week, 6-week, and 6-month rebleeding rates) and mortality after EVL. The overall recanalization (complete and partial) rate in the NWS therapy group was significantly higher than that in the control group (67.4% vs. 39.5%, P = 0.009). Low Child-Pugh score (P = 0.039, OR: 0.692, 95% CI 0.488-0.982), D-dimer < 2.00 ug/mL (P = 0.030, OR: 3.600, 95% CI 1.134-11.430), and NWS anticoagulation therapy (P = 0.002, OR: 4.189, 95% CI 1.660-10.568) were the predictors of PVT recanalization through univariate analysis of binary logistic regression. NWS anticoagulation therapy (P = 0.003, OR: 4.506, 95% CI 1.687-12.037) was the independent factor of recanalization through multivariate analysis. Nobody bled except for variceal rebleeding. Five-day failure and 14-day rebleeding were zero. There were no significantly different in 4-week (2.3% vs. 4.7%, P = 1.000), 6-week (4.7% vs. 9.3%, P = 0.672) and 6-month rebleeding (18.6% vs. 20.9%, P = 0.787) between the two groups. There was no mortality during six months follow-up. Low serum albumin (P = 0.011, OR: 0.844, 95% CI 0.741-0.962), high MELD score (P = 0.003, OR: 1.564, 95% CI 1.167-2.097) and Child-Pugh score (P = 0.006, OR: 1.950, 95% CI 1.206-3.155) were predictors of rebleeding by univariate analysis of binary logistic regression analysis. The Child-Pugh score (7 [6-8] vs. 6 [5-7], P = 0.003) and albumin levels (33.93 ± 5.30 vs. 37.28 ± 4.32, P = 0.002) were improved in the NWS therapy group at six months. In PVT patients with cirrhosis and AVB, starting NWS anticoagulation therapy early after EVL was safe and effective. It has the potential to raise albumin levels and improve liver function.
Collapse
Affiliation(s)
- Zhanjuan Gao
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China
- Department of Gastroenterology, Liaocheng People's Hospital, Liaocheng, Shandong, People's Republic of China
| | - Shanshan Li
- Department of Gastroenterology, Liaocheng People's Hospital, Liaocheng, Shandong, People's Republic of China
| | - Jingrun Zhao
- Department of Gastroenterology, Liaocheng People's Hospital, Liaocheng, Shandong, People's Republic of China
| | - Jinhou Li
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China
- Department of Gastroenterology, Taian City Central Hospital, Taian, Shandong, People's Republic of China
| | - Yanjing Gao
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
| |
Collapse
|
|
25
|
Mantaka A, Gatselis N, Triantos CK, Thalheimer U, Leandro G, Zachou K, Konstantakis C, Saitis A, Thomopoulos K, Kouroumalis EA, Dalekos GN, Samonakis DN. Treatment of portal vein thrombosis in cirrhosis: a multicenter real life cοhort study. Minerva Gastroenterol (Torino) 2023; 69:107-113. [PMID: 36856274 DOI: 10.23736/s2724-5985.21.02861-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/02/2023]
Abstract
BACKGROUND Portal vein thrombosis (PVT) is a common complication of cirrhosis and can be a cause or consequence of liver disease progression. It is unclear whether PVT treatment is affecting clinical outcomes in cirrhotics. METHODS This is a multicenter study of cirrhotics with PVT, initially retrospectively and thereafter prospectively registered in a data base. We studied the impact of PVT treatment on this population for efficacy, safety and the impact on survival. In survival analysis Mantel-Cox and Wilcoxon-Breslow-Gehan tests were used. A P value of <0.05, was considered significant. For statistical computations the STATA 12.1 was used. RESULTS Seventy-six patients were included (76% decompensated, median MELD score 12 and Child-Pugh score 7), 47% with concomitant HCC. Fifty-one patients with PVT were treated with Vitamin-K antagonists or Low-Molecular-Weight Heparin. Patients were followed up for at least 6 months after PVT diagnosis, or until death or transplantation. PV patency after 6 months was not statistically different between patients receiving or not anticoagulation (complete-partial recanalization 27.4% of treated vs. 20% of untreated, P=0.21). Median survival was statistically worse between patients treated with anticoagulation than those untreated (10 vs. 15 months, P=0.036). Less portal hypertensive bleeding and less decompensation rates were found in treated cirrhotics vs. untreated (45.8% vs. 54.2%, P=0.003 and 78% vs. 80.9%, P=0.78, respectively). Patients with HCC had worse survival when treated vs. untreated (P=0.047). CONCLUSIONS In our cohort of cirrhotics with PVT, treatment was feasible with acceptable side effects, but without meaningful clinical benefits.
Collapse
Affiliation(s)
- Aikaterini Mantaka
- Department of Gastroenterology & Hepatology, University Hospital of Heraklion, Heraklion, Crete, Greece -
| | - Nikolaos Gatselis
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
| | - Christos K Triantos
- Department of Gastroenterology, University Hospital of Patras, Patras, Greece
| | - Ulrich Thalheimer
- Department of Gastroenterology, Royal Shrewsbury Hospital, Shrewsbury, UK
| | - Gioacchino Leandro
- Department of Gastroenterology, IRCCS Saverio De Bellis Hospital, Castellana Grotte, Bari, Italy
| | - Kalliopi Zachou
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
| | | | - Asterios Saitis
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
| | | | - Elias A Kouroumalis
- Department of Gastroenterology & Hepatology, University Hospital of Heraklion, Heraklion, Crete, Greece
| | - George N Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
| | - Dimitrios N Samonakis
- Department of Gastroenterology & Hepatology, University Hospital of Heraklion, Heraklion, Crete, Greece
| |
Collapse
|
|
26
|
Caiano LM, Riva N, Ageno W. Anticoagulant therapy for splanchnic vein thrombosis: recent updates for patients with liver cirrhosis. Expert Rev Hematol 2023; 16:121-129. [PMID: 36820873 DOI: 10.1080/17474086.2023.2184340] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/24/2023]
Abstract
INTRODUCTION Liver cirrhosis is accompanied by several hemostatic alterations, which contribute to the current theory of "rebalanced hemostasis." Splanchnic vein thrombosis (SVT) is a frequent complication of liver cirrhosis (17-26% of the cirrhotic patients), and liver cirrhosis is a common risk factor for SVT (24-28% of SVT cases). AREAS COVERED This narrative review aims to describe the current state of the art on the anticoagulant treatment of cirrhotic SVT, with a particular focus on the possible role of the direct oral anticoagulants (DOACs) and recent guidelines on this topic. EXPERT OPINION Early anticoagulant therapy is recommended in cirrhotic patients with acute SVT, to obtain vessel recanalization and decrease the rates of portal hypertension-related complications. Gastroesophageal varices do not represent a contraindication to anticoagulation, if adequate prophylaxis of variceal bleeding is established, and varices band ligation can be safely performed without the need to stop the anticoagulant treatment. The conventional treatment of cirrhotic SVT consisted of low molecular weight heparin, as initial treatment of choice, eventually followed by vitamin K antagonists, but the DOACs can be considered as a reasonable alternative in patients with compensated liver cirrhosis.
Collapse
Affiliation(s)
- Lucia M Caiano
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Nicoletta Riva
- Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
| | - Walter Ageno
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
| |
Collapse
|
|
27
|
Zhong X, Li S, Hu J, Lu J, Wang W, Hu M, Sun Q, Zhang S, Yang X, Yang C, Zhong L. Development and external validation of prognostic scoring models for portal vein thrombosis: a multicenter retrospective study. Thromb J 2023; 21:9. [PMID: 36691024 PMCID: PMC9869608 DOI: 10.1186/s12959-023-00455-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Accepted: 01/18/2023] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND Portal vein thrombosis is a common complication of liver cirrhosis and hepatocellular carcinoma; however, few studies have reported its long-term clinical prognosis. This study aimed to establish and validate easy-to-use nomograms for predicting gastrointestinal bleeding, portal vein thrombosis resolution, and mortality of patients with portal vein thrombosis. METHODS This multicenter retrospective cohort study included 425 patients with portal vein thrombosis who were divided into training (n = 334) and validation (n = 91) sets. Prediction models were developed using multivariate Cox regression analysis and evaluated using the consistency index and calibration plots. RESULTS Predictors of gastrointestinal bleeding included a history of gastrointestinal bleeding, superior mesenteric vein thrombosis, red color sign observed during endoscopy, and hepatic encephalopathy. Meanwhile, predictors of resolution of portal vein thrombosis included a history of abdominal infection, C-reactive protein and hemoglobin levels, and intake of thrombolytics. Predictors of death included abdominal infection, abdominal surgery, aspartate aminotransferase level, hepatic encephalopathy, and ascites. All models had good discriminatory power and consistency. Anticoagulation therapy significantly increased the probability of thrombotic resolution without increasing the risk of bleeding or death. CONCLUSIONS We successfully developed and validated three prediction models that can aid in the early evaluation and treatment of portal vein thrombosis.
Collapse
Affiliation(s)
- Xuan Zhong
- Present Address: Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150, Jimo Road, Pudong New Area, Shanghai, 200120 China
| | - Shan Li
- Present Address: Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150, Jimo Road, Pudong New Area, Shanghai, 200120 China
| | - Jiali Hu
- Present Address: Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150, Jimo Road, Pudong New Area, Shanghai, 200120 China
| | - Jinlai Lu
- Present Address: Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150, Jimo Road, Pudong New Area, Shanghai, 200120 China
| | - Wei Wang
- Present Address: Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150, Jimo Road, Pudong New Area, Shanghai, 200120 China
| | - Miao Hu
- Present Address: Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150, Jimo Road, Pudong New Area, Shanghai, 200120 China
| | - Qinjuan Sun
- Present Address: Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150, Jimo Road, Pudong New Area, Shanghai, 200120 China
| | - Shuo Zhang
- Present Address: Department of Gastroenterology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xiaoqing Yang
- Present Address: Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150, Jimo Road, Pudong New Area, Shanghai, 200120 China
| | - Changqing Yang
- Present Address: Department of Gastroenterology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Lan Zhong
- Present Address: Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150, Jimo Road, Pudong New Area, Shanghai, 200120 China
| |
Collapse
|
|
28
|
Cutolo C, Fusco R, Simonetti I, De Muzio F, Grassi F, Trovato P, Palumbo P, Bruno F, Maggialetti N, Borgheresi A, Bruno A, Chiti G, Bicci E, Brunese MC, Giovagnoni A, Miele V, Barile A, Izzo F, Granata V. Imaging Features of Main Hepatic Resections: The Radiologist Challenging. J Pers Med 2023; 13:jpm13010134. [PMID: 36675795 PMCID: PMC9862253 DOI: 10.3390/jpm13010134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 12/31/2022] [Accepted: 01/06/2023] [Indexed: 01/12/2023] Open
Abstract
Liver resection is still the most effective treatment of primary liver malignancies, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), and of metastatic disease, such as colorectal liver metastases. The type of liver resection (anatomic versus non anatomic resection) depends on different features, mainly on the type of malignancy (primary liver neoplasm versus metastatic lesion), size of tumor, its relation with blood and biliary vessels, and the volume of future liver remnant (FLT). Imaging plays a critical role in postoperative assessment, offering the possibility to recognize normal postoperative findings and potential complications. Ultrasonography (US) is the first-line diagnostic tool to use in post-surgical phase. However, computed tomography (CT), due to its comprehensive assessment, allows for a more accurate evaluation and more normal findings than the possible postoperative complications. Magnetic resonance imaging (MRI) with cholangiopancreatography (MRCP) and/or hepatospecific contrast agents remains the best tool for bile duct injuries diagnosis and for ischemic cholangitis evaluation. Consequently, radiologists should be familiar with the surgical approaches for a better comprehension of normal postoperative findings and of postoperative complications.
Collapse
Affiliation(s)
- Carmen Cutolo
- Department of Medicine, Surgery and Dentistry, University of Salerno, 84084 Salerno, Italy
| | - Roberta Fusco
- Medical Oncology Division, Igea SpA, 80013 Napoli, Italy
- Correspondence:
| | - Igino Simonetti
- Division of Radiology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, 80131 Naples, Italy
| | - Federica De Muzio
- Department of Medicine and Health Sciences “V. Tiberio”, University of Molise, 86100 Campobasso, Italy
| | - Francesca Grassi
- Division of Radiology, Università degli Studi della Campania Luigi Vanvitelli, 80127 Naples, Italy
| | - Piero Trovato
- Division of Radiology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, 80131 Naples, Italy
| | - Pierpaolo Palumbo
- Department of Diagnostic Imaging, Area of Cardiovascular and Interventional Imaging, Abruzzo Health Unit 1, 67100 L’Aquila, Italy
- Italian Society of Medical and Interventional Radiology (SIRM), SIRM Foundation, Via della Signora 2, 20122 Milan, Italy
| | - Federico Bruno
- Department of Diagnostic Imaging, Area of Cardiovascular and Interventional Imaging, Abruzzo Health Unit 1, 67100 L’Aquila, Italy
- Italian Society of Medical and Interventional Radiology (SIRM), SIRM Foundation, Via della Signora 2, 20122 Milan, Italy
| | - Nicola Maggialetti
- Department of Medical Science, Neuroscience and Sensory Organs (DSMBNOS), University of Bari “Aldo Moro”, 70124 Bari, Italy
| | - Alessandra Borgheresi
- Department of Radiology, University Hospital “Azienda Ospedaliera Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy
- Department of Clinical, Special and Dental Sciences, University Politecnica delle Marche, Via Conca 71, 60126 Ancona, Italy
| | - Alessandra Bruno
- Department of Radiology, University Hospital “Azienda Ospedaliera Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy
- Department of Clinical, Special and Dental Sciences, University Politecnica delle Marche, Via Conca 71, 60126 Ancona, Italy
| | - Giuditta Chiti
- Italian Society of Medical and Interventional Radiology (SIRM), SIRM Foundation, Via della Signora 2, 20122 Milan, Italy
- Department of Emergency Radiology, University Hospital Careggi, Largo Brambilla 3, 50134 Florence, Italy
| | - Eleonora Bicci
- Italian Society of Medical and Interventional Radiology (SIRM), SIRM Foundation, Via della Signora 2, 20122 Milan, Italy
- Department of Emergency Radiology, University Hospital Careggi, Largo Brambilla 3, 50134 Florence, Italy
| | - Maria Chiara Brunese
- Department of Medicine and Health Sciences “V. Tiberio”, University of Molise, 86100 Campobasso, Italy
| | - Andrea Giovagnoni
- Department of Radiology, University Hospital “Azienda Ospedaliera Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy
- Department of Clinical, Special and Dental Sciences, University Politecnica delle Marche, Via Conca 71, 60126 Ancona, Italy
| | - Vittorio Miele
- Italian Society of Medical and Interventional Radiology (SIRM), SIRM Foundation, Via della Signora 2, 20122 Milan, Italy
- Department of Emergency Radiology, University Hospital Careggi, Largo Brambilla 3, 50134 Florence, Italy
| | - Antonio Barile
- Department of Applied Clinical Sciences and Biotechnology, University of L’Aquila, 67100 L’Aquila, Italy
| | - Francesco Izzo
- Division of Epatobiliary Surgical Oncology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, 80131 Naples, Italy
| | - Vincenza Granata
- Division of Radiology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, 80131 Naples, Italy
| |
Collapse
|
|
29
|
Doycheva I, Izzy M, Watt KD. Cardiovascular assessment before liver transplantation. CARDIO-HEPATOLOGY 2023:309-326. [DOI: 10.1016/b978-0-12-817394-7.00005-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
30
|
Ma J, Chalasani NP, Schwantes-An L, Björnsson ES. Review article: the safety of anticoagulants and antiplatelet agents in patients with cirrhosis. Aliment Pharmacol Ther 2023; 57:52-71. [PMID: 36373544 DOI: 10.1111/apt.17297] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 07/26/2022] [Accepted: 10/27/2022] [Indexed: 11/16/2022]
Abstract
Patients with cirrhosis were long thought to be coagulopathic. However, this paradigm has changed in recent years and currently, cirrhosis is recognised as a prothrombotic state. Due to the increasing incidence of cirrhosis from nonalcoholic steatohepatitis which is closely associated with cardiac disease, patients with cirrhosis increasingly require therapy with anticoagulants and antiplatelet agents. However, their potential for causing catastrophic and life-threatening bleeding in patients with cirrhosis leads to hesitancy about their use in patients with cirrhosis. Overall, traditional anticoagulation is safe for all Child-Pugh classes while newer direct oral anticoagulants (DOACs) are mostly safe in Child-Pugh class A/B and contraindicated in severe hepatic impairment. For different indications, published data to date suggest that anticoagulation is overall safe for patients with cirrhosis who have venous thromboembolism, atrial fibrillation and portal vein thrombosis, and does not increase the risk of variceal bleeding. Moreover, DOACs appear to have similar safety profiles as traditional anticoagulants. Finally, most studies suggest that antiplatelet agents are also safe to use in patients with cirrhosis although they are mostly contraindicated in severe hepatic impairment. For both anticoagulants and antiplatelet agents, severe thrombocytopaenia presents a relative contraindication to their use. More prospective trials and large cohort studies are needed to advance our understanding of the safety and nuances of DOACs and antiplatelet agents in patients with advanced cirrhosis.
Collapse
Affiliation(s)
- Jiayi Ma
- Indiana University School of Medicine and Indiana University Health, Indianapolis, Indiana, USA
| | - Naga P Chalasani
- Indiana University School of Medicine and Indiana University Health, Indianapolis, Indiana, USA
| | - Linus Schwantes-An
- Indiana University School of Medicine, Medical & Molecular Genetics, Indianapolis, Indiana, USA
| | - Einar Stefán Björnsson
- Department of Gastroenterology, Landspitali University Hospital, Reykjavik, Iceland.,Faculty of Medicine, University of Iceland, Reykjavik, Iceland
| |
Collapse
|
|
31
|
El-Hady HA, Mahmoud Abd-Elwahab ES, Mostafa-Hedeab G, Shawky Elfarargy M. Portal vein thrombosis in patients with COVID-19: A systematic review. Asian J Surg 2022:S1015-9584(22)01547-0. [PMID: 36435627 PMCID: PMC9650574 DOI: 10.1016/j.asjsur.2022.11.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 09/25/2022] [Accepted: 11/03/2022] [Indexed: 11/13/2022] Open
Abstract
Several studies have proven that COVID-19 is linked to a higher incidence of different thrombotic events. Thrombosis of the portal vein can result in portal hypertension and can extend to the mesenteric vein resulting in intestinal ischemia. A search of PubMed, Web of Science, and Scopus for relevant studies revealed an association between PVT and COVID-19. This review is structured according to PRISMA guidelines. Thirty-three studies met the inclusion criteria. Twenty-nine case studies/series and four cohort/cross-sectional studies were included. Age at diagnosis was lower when compared to PVT due to cirrhosis. In cohort/cross-sectional studies, males comprised 54.83% of subjects, whereas in case reports/series, males comprised 62.1%. Obesity, asthma, hypertension, and diabetes were the most common comorbidities identified. The majority of the thrombotic events occurred within two weeks. The treatment aimed to prevent thrombus progression and improve recanalization. According to the evidence, early intervention prevents the poor prognosis of intestinal ischemia and its propagation.
Collapse
Affiliation(s)
- Hany Abdelfatah El-Hady
- Department of Surgery, Faculty of Medicine, Jouf University, Saudi Arabia; Department of Surgery, Faculty of Medicine for Girls, Al-Azhar University, Egypt.
| | | | - Gomaa Mostafa-Hedeab
- Pharmacology Department, Medical College, Jouf University, Sakaka, Saudi Arabia; Pharmacology Department, Faculty of Medicine, Beni-suef University, Egypt
| | - Mohamed Shawky Elfarargy
- Department of Pediatrics, College of Medicine, Jouf University, Saudi Arabia; Department of Pediatrics, Faculty of Medicine, Tanta University, Egypt
| |
Collapse
|
|
32
|
Odriozola A, Puente Á, Cuadrado A, Rivas C, Anton Á, González FJ, Pellón R, Fábrega E, Crespo J, Fortea JI. Portal Vein Thrombosis in the Setting of Cirrhosis: A Comprehensive Review. J Clin Med 2022; 11:6435. [PMID: 36362663 PMCID: PMC9655000 DOI: 10.3390/jcm11216435] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Revised: 10/26/2022] [Accepted: 10/28/2022] [Indexed: 08/06/2023] Open
Abstract
Portal vein thrombosis constitutes the most common thrombotic event in patients with cirrhosis, with increased rates in the setting of advanced liver disease. Despite being a well-known complication of cirrhosis, the contribution of portal vein thrombosis to hepatic decompensation and overall mortality is still a matter of debate. The incorporation of direct oral anticoagulants and new radiological techniques for portal vein recanalization have expanded our therapeutic arsenal. However, the lack of large prospective observational studies and randomized trials explain the heterogenous diagnostic and therapeutic recommendations of current guidelines. This article seeks to make a comprehensive review of the pathophysiology, clinical features, diagnosis, and treatment of portal vein thrombosis in patients with cirrhosis.
Collapse
Affiliation(s)
- Aitor Odriozola
- Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, 39008 Santander, Spain
| | - Ángela Puente
- Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, 39008 Santander, Spain
| | - Antonio Cuadrado
- Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, 39008 Santander, Spain
| | - Coral Rivas
- Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, 39008 Santander, Spain
| | - Ángela Anton
- Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, 39008 Santander, Spain
| | | | - Raúl Pellón
- Radiology Department, Marqués de Valdecilla University Hospital, 39008 Santander, Spain
| | - Emilio Fábrega
- Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, 39008 Santander, Spain
| | - Javier Crespo
- Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, 39008 Santander, Spain
| | - José Ignacio Fortea
- Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, 39008 Santander, Spain
| |
Collapse
|
|
33
|
Zhao JW, Cui XH, Zhao WY, Wang L, Xing L, Jiang XY, Gong X, Yu L. Acute mesenteric ischemia secondary to oral contraceptive-induced portomesenteric and splenic vein thrombosis: A case report. World J Clin Cases 2022; 10:10629-10637. [PMID: 36312508 PMCID: PMC9602218 DOI: 10.12998/wjcc.v10.i29.10629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 06/21/2022] [Accepted: 09/01/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Mesenteric ischemia represents an uncommon complication of splanchnic vein thrombosis, and it is less infrequently seen in young women using oral contraceptives. Diagnosis is often delayed in the emergency room; thus, surgical intervention may be inevitable and the absence of thrombus regression or collateral circulation may lead to further postoperative ischemia and a fatal outcome. CASE SUMMARY We report a 28-year-old female patient on oral contraceptives who presented with acute abdominal pain. Her physical examination findings were not consistent with her symptoms of severe pain and abdominal distention. These findings and her abnormal blood tests raised suspicion of acute mesenteric ischemia (AMI) induced by splanchnic vein thrombosis. Contrast-enhanced abdominal computed tomography revealed ischemia of the small intestine with portomesenteric and splenic vein thrombosis (PMSVT). We treated the case promptly by anticoagulation after diagnosis. We then performed delayed segmental bowel resection after thrombus regression and established collateral circulation guided by collaboration with a multidisciplinary team. The patient had an uneventful postoperative course and was discharged 14 d after surgery and took rivaroxaban orally for 6 mo. In subsequent follow-up to date, the patient has not complained of any other discomfort. CONCLUSION AMI induced by PMSVT should be considered in young women who are taking oral contraceptives and have acute abdominal pain. Prompt anticoagulation followed by surgery is an effective treatment strategy.
Collapse
Affiliation(s)
- Jin-Wei Zhao
- Department of Hepatopancreatobiliary Surgery of Second Hospital of Jilin University, State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of The Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130000, Jilin Province, China
| | - Xin-Hua Cui
- Department of Hepatopancreatobiliary Surgery of Second Hospital of Jilin University, State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of The Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130000, Jilin Province, China
| | - Wei-Yi Zhao
- Department of Hepatopancreatobiliary Surgery of Second Hospital of Jilin University, State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of The Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130000, Jilin Province, China
- Medical College of Yanbian University, Yanbian 133002, Jilin Province, China
| | - Lei Wang
- Department of Imaging Surgery of Second Hospital of Jilin University, Jilin University, Changchun 130000, Jilin Province, China
| | - Lin Xing
- Department of Hepatopancreatobiliary Surgery of Second Hospital of Jilin University, State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of The Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130000, Jilin Province, China
| | - Xue-Yuan Jiang
- Department of Hepatopancreatobiliary Surgery of Second Hospital of Jilin University, State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of The Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130000, Jilin Province, China
| | - Xue Gong
- Department of Imaging Surgery of Second Hospital of Jilin University, Jilin University, Changchun 130000, Jilin Province, China
| | - Lu Yu
- Department of Hepatopancreatobiliary Surgery of Second Hospital of Jilin University, State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of The Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130000, Jilin Province, China
| |
Collapse
|
|
34
|
Zhao Y, Zhu L, Yang Y, Gao H, Zhang R. Safety of direct oral anticoagulants in patients with liver disease: a systematic review and meta-analysis. Acta Clin Belg 2022; 78:234-244. [PMID: 35913111 DOI: 10.1080/17843286.2022.2108259] [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: 10/16/2022]
Abstract
BACKGROUND Direct oral anticoagulants (DOACs), such as apixaban, edoxaban, rivaroxaban, or dabigatran, are an effective treatment for atrial fibrillation (AF) and deep venous thromboembolism. We hope to evaluate the safety of DOACs versus warfarin/low molecular weight heparin (LMWH) in improving bleeding events in patients with different severity of the liver disease. METHODS We systematically searched the Cochrane Library, PubMed, and Embase databases for studies reporting the effects of DOACs in patients with liver cirrhosis. A random-effects model or fixed-effects model was selected to pool risk ratios (RR) and 95% confidence intervals (CI). RESULTS A total of 18 studies involving 41,447 participants was included in this meta-analysis. Compare with warfarin/ LMWH, the use of DOACs significantly reduced the incidence of all bleeding (RR: 0.76; 95%CI: 0.66 to 0.87), major bleeding (RR: 0.51; 95%CI: 0.28 to 0.91), intracranial hemorrhage (RR: 0.50; 95%CI: 0.31 to 0.81), and gastrointestinal bleeding (RR: 0.76, 95% CI: 0.60 to 0.97), and all-cause death in patients with liver disease (RR: 0.77; 95%CI: 0.62 to 0.95). Similar results were observed in atrial fibrillation patients with liver disease and cirrhosis subgroups. Furthermore, the pooled estimates of the Child-Turcotte-Pugh (CTP) class indicated that DOACs reduced the incidence of all bleeding (RR: 0.61; 95%CI: 0.45 to 0.82), gastrointestinal bleeding (RR 0.55; 95%CI: 0.37 to 0.83), and all-cause death (RR: 0.62; 95%CI: 0.49 to 0.79) in patients with mild to moderate cirrhosis. CONCLUSIONS Our study demonstrates that DOACs significantly reduce the risk of bleeding in patients with liver disease compared with warfarin/LMWH.
Collapse
Affiliation(s)
- Yan Zhao
- Department of Hepatology, The Fourth Hospital of Huai'an, Huai'an, Jiangsu, China
| | - Liyao Zhu
- Department of Hepatology, The Fourth Hospital of Huai'an, Huai'an, Jiangsu, China
| | - Yang Yang
- Department of Hepatology, The Fourth Hospital of Huai'an, Huai'an, Jiangsu, China
| | - Han Gao
- Department of Hepatology, The Fourth Hospital of Huai'an, Huai'an, Jiangsu, China
| | - Rui Zhang
- Department of Hepatology, The Fourth Hospital of Huai'an, Huai'an, Jiangsu, China
| |
Collapse
|
|
35
|
Splanchnic vein thrombosis associated with myeloproliferative neoplasms. Thromb Res 2022; 218:8-16. [PMID: 35963121 DOI: 10.1016/j.thromres.2022.08.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 06/30/2022] [Accepted: 08/03/2022] [Indexed: 11/22/2022]
|
|
36
|
Zhang SB, Hu ZX, Xing ZQ, Li A, Zhou XB, Liu JH. Portal vein thrombosis in a noncirrhotic patient after hemihepatectomy: A case report and review of literature. World J Clin Cases 2022; 10:7130-7137. [PMID: 36051122 PMCID: PMC9297407 DOI: 10.12998/wjcc.v10.i20.7130] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 03/06/2022] [Accepted: 05/28/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Portal vein thrombosis (PVT) is a condition caused by hemodynamic disorders. It may be noted in the portal vein system when there is an inflammatory stimulus in the abdominal cavity. However, PVT is rarely reported after hepatectomy. At present, related guidelines and major expert opinions tend to consider vitamin K antagonists or low-molecular weight heparin (LMWH) as the standard treatment. But based on research, direct oral anticoagulants may be more effective and safe for noncirrhotic PVT and are also beneficial by reducing the recurrence rate of PVT.
CASE SUMMARY A 51-year-old woman without any history of disease felt discomfort in her right upper abdomen for 20 d, with worsening for 7 d. Contrast-enhanced computed tomography (CECT) of the upper abdomen showed right liver intrahepatic cholangiocarcinoma with multiple intrahepatic metastases but not to the left liver. Therefore, she underwent right hepatic and caudate lobectomy. One week after surgery, the patient underwent a CECT scan, due to nausea, vomiting, and abdominal distension. Thrombosis in the left branch and main trunk of the portal vein and near the confluence of the splenic vein was found. After using LMWH for 22 d, CECT showed no filling defect in the portal vein system.
CONCLUSION Although PVT after hepatectomy is rare, it needs to be prevented during the perioperative period.
Collapse
Affiliation(s)
- Shu-Bin Zhang
- Department of Hepatobiliary Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Zi-Xuan Hu
- Department of Hepatobiliary Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Zhong-Qiang Xing
- Department of Hepatobiliary Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Ang Li
- Department of Hepatobiliary Surgery, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Xin-Bo Zhou
- Department of Hepatobiliary Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Jian-Hua Liu
- Department of Hepatobiliary Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| |
Collapse
|
|
37
|
Oldham M, Palkimas S, Hedrick A. Safety and Efficacy of Direct Oral Anticoagulants in Patients With Moderate to Severe Cirrhosis. Ann Pharmacother 2022; 56:782-790. [PMID: 34553626 DOI: 10.1177/10600280211047433] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Direct oral anticoagulants (DOACs) remain mostly investigational in patients with moderate to severe hepatic cirrhosis, yet are often selected over traditional anticoagulants including warfarin and enoxaparin in this setting. OBJECTIVE To determine the safety and efficacy of DOACs in patients with moderate to severe hepatic cirrhosis as compared with traditional anticoagulation. METHODS This was a retrospective, single-center cohort study evaluating inpatients and outpatients who were prescribed a DOAC, warfarin, or enoxaparin for therapeutic anticoagulation with Child-Turcotte-Pugh (CTP) B or C status at the time that the prescription was written. Included patients were followed until first bleeding or thromboembolic event, or until discontinuation of anticoagulation therapy. Data were collected by manual chart review. The primary outcomes included both bleeding events and thromboembolic events in the DOAC population as compared with traditional anticoagulation. RESULTS A total of 101 patients were included in the study, 69 treated with DOAC therapy and 32 with traditional anticoagulation. Bleeding events occurred in 36% of patients in the DOAC group and 22% of patients in the traditional group (P = 0.149). In both groups, bleeds were most commonly gastrointestinal. Thromboembolic events occurred in 4% of the DOAC population and no patients in the traditional population (P = 0.55). No fatal bleeding or thromboembolic events occurred. CONCLUSION AND RELEVANCE DOACs do not appear to be more harmful than traditional anticoagulation in patients with CTP B or C status. These results support the use of DOACs in patients with CTP B or C hepatic cirrhosis when considering safety, efficacy, and convenience.
Collapse
|
|
38
|
Martens K, McMurry HS, Koprowski S, Hum J, Haraga J, Jou JH, Shatzel JJ. Anticoagulation in Cirrhosis: Evidence for the Treatment of Portal Vein Thrombosis and Applications for Prophylactic Therapy. J Clin Gastroenterol 2022; 56:536-545. [PMID: 35537133 PMCID: PMC9189067 DOI: 10.1097/mcg.0000000000001713] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The clinical utility of anticoagulation for patients with cirrhosis and asymptomatic portal vein thrombosis (PVT) is widely debated. Complex hemostatic derangements in cirrhosis that increase risk of both bleeding and thrombosis, as well as a lack of randomized controlled data, limit conclusive assessments regarding optimal management of anticoagulation in this setting. In this review, we summarize the relevant literature pertaining to PVT in cirrhosis, including the effect of untreated PVT on the natural progression of liver disease and the overall impact of anticoagulation on clot burden and other relevant clinical outcomes. Apart from patients who are symptomatic or listed for liver transplantation, data supporting anticoagulation for the treatment of PVT is limited and without clear consensus guidelines. In patients with cirrhosis without PVT, emerging evidence for the role of prophylactic anticoagulation to mitigate the progression of fibrosis suggests an optimal risk-benefit tradeoff with decreased rates of liver decompensation and mortality, without a heightened risk of bleeding. In summation, as our understanding of the role of both prophylactic and therapeutic anticoagulation in cirrhosis continues to evolve, ongoing risk stratification of patients with asymptomatic PVT demands further attention.
Collapse
Affiliation(s)
- Kylee Martens
- Division of Hematology-Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland OR
| | | | - Steven Koprowski
- Division of Gastroenterology, Oregon Health & Science University, Portland OR
| | - Justine Hum
- Division of Gastroenterology, Oregon Health & Science University, Portland OR
| | - Jessica Haraga
- Division of Gastroenterology, University of California, Los Angeles, CA
| | - Janice H. Jou
- Division of Gastroenterology, Oregon Health & Science University, Portland OR
| | - Joseph J. Shatzel
- Division of Hematology-Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland OR
| |
Collapse
|
|
39
|
Anticoagulant therapy for splanchnic vein thrombosis: an individual patient data meta-analysis. Blood Adv 2022; 6:4516-4523. [PMID: 35613465 DOI: 10.1182/bloodadvances.2022007961] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 05/10/2022] [Indexed: 11/20/2022] Open
Abstract
Robust evidence on the optimal management of splanchnic vein thrombosis (SVT) is lacking. We conducted an individual patient meta-analysis to evaluate the effectiveness and safety of anticoagulation for splanchnic vein thrombosis (SVT). MEDLINE, EMBASE, and clincaltrials.gov., were searched up to June 2021 for prospective cohorts or randomized clinical trials including patients with SVT. Data from individual datasets were merged, and any discrepancy with published data was resolved by contacting study authors. Three studies for a total of 1635 patients were included. Eighty-five percent of patients received anticoagulation for a median duration of 316 days (range 1 to 730 days). Overall, incidence rates for recurrent VTE, major bleeding, and mortality were 5.3/100 patients-years (p-y) (95% CI, 5.1 to 5.5), 4.4/100 p-y (95% CI, 4.2 to 4.6), and 13.0/100 p-y (95% CI, 12.4 to 13.6), respectively. The incidence rates of all outcomes were lower during anticoagulation and higher after treatment discontinuation or when anticoagulation was not administered. In multivariable analysis, anticoagulant treatment appeared to be associated with a lower risk of recurrent VTE (Hazard Ratio [HR] 0.42; 95% CI, 0.27 to 0.64), major bleeding (HR 0.47; 95% CI, 0.30 to 0.74), and mortality (HR 0.23; 95% CI, 0.17 to 0.31). Results were consistent in patients with cirrhosis, solid cancer, myeloproliferative neoplasms, unprovoked SVT, and SVT associated with transient or persistent non-malignant risk factors. In patients with SVT the risk of recurrent VTE and major bleeding is substantial. Anticoagulant treatment is associated with reduced risk of both outcomes.
Collapse
|
|
40
|
Coons EM, Staubes BA, Casey AL, Elagizi-Youssef SA, Mohammed AE, Sharma N, Kline ER. Direct Oral Anticoagulants Versus Warfarin for Treatment of Thrombosis or Atrial Fibrillation in Patients With Cirrhosis: A Retrospective Cohort Study. Ann Pharmacother 2022; 56:533-540. [PMID: 34470525 DOI: 10.1177/10600280211025050] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Evidence for direct oral anticoagulants (DOACs) in patients with cirrhosis is limited. Few patients with Child-Turcotte-Pugh (CTP) class B and C cirrhosis have been studied. OBJECTIVE To compare major bleeding rates in patients with cirrhosis receiving a DOAC versus warfarin. METHODS A retrospective cohort study was conducted in adults with cirrhosis receiving a DOAC versus warfarin for venous thromboembolism, portal-vein thrombosis, or atrial fibrillation. The primary outcome was the rate of major bleeding. Secondary outcomes included time to major bleeding, clinically relevant nonmajor bleeding, all bleeding, gastrointestinal bleeding, intracranial bleeding, and new thromboembolic events. The study was approved by the Ochsner Health System Institutional Review Board. RESULTS A total of 44 patients receiving a DOAC and 41 patients receiving warfarin were included. Major bleeding occurred in 4 patients receiving a DOAC and 6 patients receiving warfarin (9.1% vs 14.6%; P = 0.881). Rates of major bleeding were similar in 24 DOAC and 17 warfarin patients with CTP Class B (4.2% vs 17.6%; P = 0.37) and 8 DOAC and 9 warfarin patients with CTP Class C (37.5% vs 11.1%; P = 0.41) cirrhosis. Secondary bleeding and efficacy outcomes were similar between cohorts. The study was limited by a small sample size. CONCLUSION AND RELEVANCE Treatment with DOACs in patients with cirrhosis was associated with a similar rate of major bleeding compared with warfarin. Inclusion of CTP class C patients in future studies remains valuable to evaluate safety and efficacy of DOACs in this population.
Collapse
|
|
41
|
Abstract
Patients with cirrhosis of the liver are at high risk of developing portal vein thrombosis (PVT), which has a complex, multifactorial cause. The condition may present with a myriad of symptoms and can occasionally cause severe complications. Contrast-enhanced computed tomography (CT) is the gold standard for the diagnosis of PVT. There are uncertainties regarding the effect on PVT and its treatment outcome in patients with cirrhosis. The main challenge for managing PVT in cirrhosis is analyzing the risk of hemorrhage compared to the risk of thrombus extension leading to complications. All current knowledge regarding non-tumor PVT in cirrhosis, including epidemiology, risk factors, classification, clinical presentation, diagnosis, impact on natural history, and treatment, is discussed in the present article.
Collapse
Key Words
- ACLF, acute-on-chronic liver failure
- BCS, Budd–Chiari syndrome
- DOACs, direct-acting oral anticoagulants
- EASL, European Association for the Study of the Liver
- HCC, hepatocellular carcinoma
- HVPG, hepatic venous pressure gradient
- INR, international normalized ratio
- JAK2, Janus Kinase 2
- LMWH, low molecular weight heparin
- LT, liver transplant
- MELD, Model for End-Stage Liver Disease
- MTHFR, methyltetrahydrofolate reductase
- NASH, non-alcoholic steatohepatitis
- NO, nitric oxide
- NSBBs, non-selective beta-blockers
- PV, portal vein
- PVT, Portal vein thrombosis
- RCT, randomized controlled trial
- SMA, superior mesenteric artery
- SMV, superior mesenteric vein
- SVT, splanchnic vein thrombosis
- TIPS, Transjugular intrahepatic portosystemic shunt
- UNOS, United Network for Organ Sharing
- VEGF, vascular endothelial growth factors
- VKAs, vitamin K antagonists
- VKORC1, vitamin K epoxide reductase complex 1
- anticoagulation
- cirrhosis
- eNOS, endothelial nitric oxide synthase
- non-tumoral portal vein thrombosis
- portal hypertension
- rTPA, recombinant tissue plasminogen activator
- transjugular intrahepatic portosystemic shunt
- vWF, von Willebrand factor
Collapse
Affiliation(s)
- Akash Shukla
- Department of Gastroenterology, Seth GS Medical College and KEM Hospital, Mumbai, India
| | - Suprabhat Giri
- Department of Gastroenterology, Seth GS Medical College and KEM Hospital, Mumbai, India
| |
Collapse
|
|
42
|
Villa E, Bianchini M, Blasi A, Denys A, Giannini EG, de Gottardi A, Lisman T, de Raucourt E, Ripoll C, Rautou PE. EASL Clinical Practice Guidelines on prevention and management of bleeding and thrombosis in patients with cirrhosis. J Hepatol 2022; 76:1151-1184. [PMID: 35300861 DOI: 10.1016/j.jhep.2021.09.003] [Citation(s) in RCA: 176] [Impact Index Per Article: 58.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 09/13/2021] [Indexed: 12/11/2022]
Abstract
The prevention and management of bleeding and thrombosis in patients with cirrhosis poses several difficult clinical questions. These Clinical Practice Guidelines have been developed to provide practical guidance on debated topics, including current views on haemostasis in liver disease, controversy regarding the need to correct thrombocytopenia and abnormalities in the coagulation system in patients undergoing invasive procedures, and the need for thromboprophylaxis in hospitalised patients with haemostatic abnormalities. Multiple recommendations in this document are based on interventions that the panel feels are not useful, even though widely applied in clinical practice.
Collapse
|
|
43
|
Biolato M, Paratore M, Di Gialleonardo L, Marrone G, Grieco A. Direct oral anticoagulant administration in cirrhotic patients with portal vein thrombosis: What is the evidence? World J Hepatol 2022; 14:682-695. [PMID: 35646264 PMCID: PMC9099104 DOI: 10.4254/wjh.v14.i4.682] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 09/22/2021] [Accepted: 04/03/2022] [Indexed: 02/06/2023] Open
Abstract
In recent years, the traditional concept that cirrhosis-related coagulopathy is an acquired bleeding disorder has evolved. Currently, it is known that in cirrhotic patients, the hemostatic system is rebalanced, which involves coagulation factors, fibrinolysis and platelets. These alterations disrupt homeostasis, skewing it toward a procoagulant state, which can lead to thromboembolic manifestations, especially when hemodynamic and endothelial factors co-occur, such as in the portal vein system in cirrhosis. Portal vein thrombosis is a common complication of advanced liver cirrhosis that negatively affects the course of liver disease, prognosis of cirrhotic patients and success of liver transplantation. It is still debated whether portal vein thrombosis is the cause or the consequence of worsening liver function. Anticoagulant therapy is the mainstay treatment for acute symptomatic portal vein thrombosis. In chronic portal vein thrombosis, the role of anticoagulant therapy is still unclear. Traditional anticoagulants, vitamin K antagonists and low-molecular-weight heparin are standard-of-care treatments for portal vein thrombosis. In the last ten years, direct oral anticoagulants have been approved for the prophylaxis and treatment of many thromboembolic-related diseases, but evidence on their use in cirrhotic patients is very limited. The aim of this review was to summarize the evidence about the safety and effectiveness of direct oral anticoagulants for treating portal vein thrombosis in cirrhotic patients.
Collapse
Affiliation(s)
- Marco Biolato
- Internal and Liver Transplant Medicine Unit, CEMAD, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
- Institute of Internal Medicine, Catholic University of Sacred Heart, Rome 00168, Italy.
| | - Mattia Paratore
- Institute of Internal Medicine, Catholic University of Sacred Heart, Rome 00168, Italy
| | - Luca Di Gialleonardo
- Institute of Internal Medicine, Catholic University of Sacred Heart, Rome 00168, Italy
| | - Giuseppe Marrone
- Internal and Liver Transplant Medicine Unit, CEMAD, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
- Institute of Internal Medicine, Catholic University of Sacred Heart, Rome 00168, Italy
| | - Antonio Grieco
- Internal and Liver Transplant Medicine Unit, CEMAD, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
- Institute of Internal Medicine, Catholic University of Sacred Heart, Rome 00168, Italy
| |
Collapse
|
|
44
|
Rivaroxaban for the treatment of noncirrhotic splanchnic vein thrombosis: an interventional prospective cohort study. Blood Adv 2022; 6:3569-3578. [PMID: 35439303 PMCID: PMC9631568 DOI: 10.1182/bloodadvances.2022007397] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 04/05/2022] [Indexed: 11/20/2022] Open
Abstract
SVT is a potentially life-threatening disease associated with a substantial risk of recurrence and bleeding. Rivaroxaban appears to be a reasonable alternative to standard anticoagulation for the treatment of SVT in patients without cirrhosis. Heparins and vitamin K antagonists are the mainstay of treatment of splanchnic vein thrombosis (SVT). Rivaroxaban is a potential alternative, but data to support its use are limited. We aimed to evaluate the safety and efficacy of rivaroxaban for the treatment of acute SVT. In an international, single-arm clinical trial, adult patients with a first episode of noncirrhotic, symptomatic, objectively diagnosed SVT received rivaroxaban 15 mg twice daily for 3 weeks, followed by 20 mg daily for an intended duration of 3 months. Patients with Budd-Chiari syndrome and those receiving full-dose anticoagulation for >7 days prior to enrollment were excluded. Primary outcome was major bleeding; secondary outcomes included death, recurrent SVT, and complete vein recanalization within 3 months. Patients were followed for a total of 6 months. A total of 103 patients were enrolled; 100 were eligible for the analysis. Mean age was 54.4 years; 64% were men. SVT risk factors included abdominal inflammation/infection (28%), solid cancer (9%), myeloproliferative neoplasms (9%), and hormonal therapy (9%); 43% of cases were unprovoked. JAK2 V617F mutation was detected in 26% of 50 tested patients. At 3 months, 2 patients (2.1%; 95% confidence interval, 0.6-7.2) had major bleeding events (both gastrointestinal). One (1.0%) patient died due to a non–SVT-related cause, 2 had recurrent SVT (2.1%). Complete recanalization was documented in 47.3% of patients. One additional major bleeding event and 1 recurrent SVT occurred at 6 months. Rivaroxaban appears as a potential alternative to standard anticoagulation for the treatment of SVT in non-cirrhotic patients. This trial was registered at www.clinicaltrials.gov as #NCT02627053 and at eudract.ema.europa.eu as #2014-005162-29-36.
Collapse
|
|
45
|
Riat R, Gomez K. Addendum to guidelines on the investigation and management of venous thrombosis at unusual sites (Br. J. Haematol. 2012;159:28-38): Use of Direct Oral Anticoagulants. Br J Haematol 2022; 198:46-49. [PMID: 35389508 DOI: 10.1111/bjh.18189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 03/22/2022] [Accepted: 03/25/2022] [Indexed: 11/30/2022]
Affiliation(s)
- Renu Riat
- Haematology Department, Buckinghamshire NHS Trust, Amersham, UK
| | - Keith Gomez
- Haemophilia Centre and Thrombosis Unit, Royal Free London NHS Foundation Trust, London, UK
| | | |
Collapse
|
|
46
|
Hibi T. Nontransplant options for portomesenteric thrombosis. Curr Opin Organ Transplant 2022; 27:144-147. [PMID: 35143434 DOI: 10.1097/mot.0000000000000964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW Portomesenteric thrombosis (PMT) is a serious condition encountered mainly in cirrhotic patients awaiting liver transplantation. More recently, this potentially fatal complication has been described after bariatric surgery and inflammatory bowel disease. Several consensus guidelines have been published over the past few years and this mini review was conducted to discuss updated nontransplant treatment options based on currently available evidence. RECENT FINDINGS Anticoagulation is the mainstay of treatment for PMT involving <50% of the main portal vein. Transjugular intrahepatic portosystemic shunt are usually preserved for patients with more extensive disease or those with clinically significant portal hypertension that are treatment refractory. SUMMARY The extent of PMT, response to therapy, and complications related with PMT are the determinants of therapy.
Collapse
Affiliation(s)
- Taizo Hibi
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| |
Collapse
|
|
47
|
Choi MJ, Kim JS, Yu H, Woo MR, Choi JE, Baek K, Kim JO, Choi YS, Choi HG, Jin SG. Comparison of the physicochemical properties, aqueous solubility, and oral bioavailability of rivaroxaban-loaded high-pressure homogenised and Shirasu porous glass membrane emulsified solid self-nanoemulsifying drug delivery systems. J Mol Liq 2022. [DOI: 10.1016/j.molliq.2021.117057] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
|
|
48
|
Senzolo M, Zanetto A. Anticoagulation in Splanchnic Vein Thrombosis With and Without Underlying Liver Disease. PORTAL HYPERTENSION VII 2022:649-667. [DOI: 10.1007/978-3-031-08552-9_57] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
49
|
Primignani M, Tosetti G. Direct oral anticoagulants for portal vein thrombosis in cirrhosis: Good news from meta-analysis? Dig Liver Dis 2022; 54:54-55. [PMID: 34688574 DOI: 10.1016/j.dld.2021.09.018] [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: 09/09/2021] [Revised: 09/29/2021] [Accepted: 09/30/2021] [Indexed: 12/11/2022]
Affiliation(s)
- M Primignani
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy.
| | - G Tosetti
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy
| |
Collapse
|
|
50
|
Sarquis LM, Trintinalha PDO, Michaelis W, Santos Filho AL, Yokoyama RA, Michaelis T, Smaniotto AP, Oliveira MS. Trombose de veia porta não associada à cirrose – desafio terapêutico. J Vasc Bras 2022; 21:e20210013. [PMID: 35399346 PMCID: PMC8958433 DOI: 10.1590/1677-5449.210013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Accepted: 12/01/2021] [Indexed: 11/22/2022] Open
Abstract
Portal vein thrombosis (PVT) is a disease in which thrombosis occurs from the intrahepatic branches of the portal vein, and may extend to the splenic vein and/or superior mesenteric vein. It is most often associated with liver cirrhosis. PVT not associated with cirrhosis is rare. The aim of this article is to report two cases of PVT in which it was not associated with cirrhosis. Both were treated with anticoagulation and clinical progress afterwards was good.
Collapse
|