Anticoagulant therapy for splanchnic vein thrombosis

Abstract

Splanchnic vein thrombosis is an unusual site venous thromboembolism (VTE) which includes portal, mesenteric, or splenic vein thrombosis, and the Budd‐Chiari syndrome.1.European Association for the Study of the LiverEASL clinical practice guidelines: vascular diseases of the liver.J Hepatol. 2016; 64: 179-202Abstract Full Text Full Text PDF PubMed Scopus (421) Google Scholar, 2.Valeriani E. Riva N. Di Nisio M. Ageno W. Splanchnic vein thrombosis: current perspectives.Vasc Health Risk Manag. 2019; 15: 449-461Crossref PubMed Scopus (40) Google Scholar The management of splanchnic vein thrombosis remains challenging and often empirical with limited evidence from observational studies and few small randomized trials.1.European Association for the Study of the LiverEASL clinical practice guidelines: vascular diseases of the liver.J Hepatol. 2016; 64: 179-202Abstract Full Text Full Text PDF PubMed Scopus (421) Google Scholar, 2.Valeriani E. Riva N. Di Nisio M. Ageno W. Splanchnic vein thrombosis: current perspectives.Vasc Health Risk Manag. 2019; 15: 449-461Crossref PubMed Scopus (40) Google Scholar The scope of this guidance document is to provide clinicians with practical advice on how to manage splanchnic vein thrombosis, identify patients who may benefit from anticoagulant treatment, and decide on the type and duration of anticoagulation. A systematic search of the literature was performed in MEDLINE and EMBASE databases, and clinical trial registries were searched to retrieve additional information from ongoing studies. Selected articles were critically appraised to formulate guidance statements on relevant clinical questions. The wording “recommend” indicates a strong guidance statement with good consensus among the panelists, whereby the clinician should consider adopting the practice in most cases. The wording “suggest” reflects a weak guidance statement with moderate consensus among the panel members, whereby the clinician may adopt the guidance statement or use an alternative approach to manage patients. The incidence of splanchnic vein thrombosis is about 25 times lower than usual site VTE (ie, deep vein thrombosis and pulmonary embolism) and varies broadly across different studies with the most and least common types represented by portal vein thrombosis and Budd‐Chiari syndrome, respectively.2.Valeriani E. Riva N. Di Nisio M. Ageno W. Splanchnic vein thrombosis: current perspectives.Vasc Health Risk Manag. 2019; 15: 449-461Crossref PubMed Scopus (40) Google Scholar, 3.Ogren M. Bergqvist D. Björck M. Acosta S. Eriksson H. Sternby N.H. Portal vein thrombosis: prevalence, patient characteristics and lifetime risk: a population study based on 23,796 consecutive autopsies.World J Gastroenterol. 2006; 12: 2115-2119Crossref PubMed Scopus (313) Google Scholar, 4.Rajani R. Björnsson E. Bergquist A. et al.The epidemiology and clinical features of portal vein thrombosis: a multicentre study.Aliment Pharmacol Ther. 2010; 32: 1154-1162Crossref PubMed Scopus (105) Google Scholar, 5.Ageno W. Dentali F. Pomero F. et al.Incidence rates and case fatality rates of portal vein thrombosis and Budd‐Chiari Syndrome.Thromb Haemost. 2017; 117: 794-800Crossref PubMed Scopus (59) Google Scholar Liver cirrhosis, solid cancer, and myeloproliferative neoplasms represent the three major risk factors for splanchnic vein thrombosis.6.Thatipelli M.R. McBane R.D. Hodge D.O. Wysokinski W.E. Survival and recurrence in patients with splanchnic vein thromboses.Clin Gastroenterol Hepatol. 2010; 8: 200-205Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar, 7.Ageno W. Riva N. Schulman S. et al.Long‐term clinical outcomes of splanchnic vein thrombosis: results of an international registry.JAMA Intern Med. 2015; 175: 1474-1480Crossref PubMed Scopus (132) Google Scholar, 8.Sogaard K.K. Adelborg K. Darvalics B. et al.Risk of bleeding and arterial cardiovascular events in patients with splanchnic vein thrombosis in Denmark: a population‐based cohort study.Lancet Haematol. 2018; 5: e441-e449Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Transient risk factors such as surgery, abdominal inflammation/infection, or hormonal replacement therapy may also be associated with splanchnic vein thrombosis, which remains unprovoked in up to one fourth of cases.6.Thatipelli M.R. McBane R.D. Hodge D.O. Wysokinski W.E. Survival and recurrence in patients with splanchnic vein thromboses.Clin Gastroenterol Hepatol. 2010; 8: 200-205Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar, 7.Ageno W. Riva N. Schulman S. et al.Long‐term clinical outcomes of splanchnic vein thrombosis: results of an international registry.JAMA Intern Med. 2015; 175: 1474-1480Crossref PubMed Scopus (132) Google Scholar A large prospective registry found a close relationship between underlying risk factors and prognosis of splanchnic vein thrombosis. Patients with thrombosis due to transient risk factors had the lowest risk of thrombotic (3.2 per 100 patient‐year) and major bleeding (0.5 per 100 patient‐year) complications, whereas patients with underlying chronic major risk factors such as liver cirrhosis had the highest incidence of events (11.3 and 10.0 per 100 patient‐year, respectively).7.Ageno W. Riva N. Schulman S. et al.Long‐term clinical outcomes of splanchnic vein thrombosis: results of an international registry.JAMA Intern Med. 2015; 175: 1474-1480Crossref PubMed Scopus (132) Google Scholar Splanchnic vein thrombosis is associated with high mortality, especially during the first month after diagnosis and in case of mesenteric vein involvement, but risk remains significant up to 5 years in patients with portal and hepatic vein thrombosis.9.Søgaard K.K. Darvalics B. Horváth‐Puhó E. Sørensen H.T. Survival after splanchnic vein thrombosis: a 20‐year nationwide cohort study.Thromb Res. 2016; 141: 1-7Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar The use of anticoagulant treatment for splanchnic vein thrombosis has been associated with significant reduction of thrombotic events and major bleeding compared with no anticoagulation.7.Ageno W. Riva N. Schulman S. et al.Long‐term clinical outcomes of splanchnic vein thrombosis: results of an international registry.JAMA Intern Med. 2015; 175: 1474-1480Crossref PubMed Scopus (132) Google Scholar Early administration of anticoagulants within the first 2 weeks after diagnosis may lead to better vessel recanalization.10.Delgado M.G. Seijo S. Yepes I. et al.Efficacy and safety of anticoagulation on patients with cirrhosis and portal vein thrombosis.Clin Gastroenterol Hepatol. 2012; 10: 776-783Abstract Full Text Full Text PDF PubMed Scopus (250) Google Scholar, 11.Turnes J. García‐Pagán J.C. González M. et al.Portal hypertension‐related complications after acute portal vein thrombosis: impact of early anticoagulation.Clin Gastroenterol Hepatol. 2008; 6: 1412-1417Abstract Full Text Full Text PDF PubMed Scopus (139) Google Scholar The decision to start and the optimal timing of anticoagulant treatment have to be balanced against the risk of bleeding, mostly gastrointestinal, which may be relevant because of the acute manifestation of splanchnic vein thrombosis, which includes venous intestinal congestion, the concomitant comorbidities, and the presence of gastroesophageal varices. An immediate evaluation by a surgical team is critical in patients with severe clinical presentation (eg shock, peritonitis, perforation, intestinal infarction, or acute major gastrointestinal bleeding) before considering anticoagulant treatment. An interdisciplinary discussion should take place to inform of any plans for surgery or invasive procedures so that anticoagulant treatment is avoided at that time. Prior to anticoagulation, clinicians should consider performing esophagogastroduodenoscopy for variceal screening in selected patients at risk of portal hypertension, medical prophylaxis with beta‐blockers, and endoscopic variceal band ligation for high‐risk varices to reduce the incidence of first and recurrent variceal bleeding.12.Cui S.B. Shu R.H. Yan S.P. et al.Efficacy and safety of anticoagulation therapy with different doses of enoxaparin for portal vein thrombosis in cirrhotic patients with hepatitis B.Eur J Gastroenterol Hepatol. 2015; 27: 914-919Crossref PubMed Scopus (61) Google Scholar, 13.Condat B. Pessione F. Hillaire S. et al.Current outcome of portal vein thrombosis in adults: risk and benefit of anticoagulant therapy.Gastroenterology. 2001; 120: 490-497Abstract Full Text Full Text PDF PubMed Scopus (397) Google Scholar, 14.Senzolo M. Sartori M.T. Rossetto V. et al.Prospective evaluation of anticoagulation and transjugular intrahepatic portosystemic shunt for the management of portal vein thrombosis in cirrhosis.Liver Int. 2012; 32: 919-927Crossref PubMed Scopus (228) Google Scholar After medical prophylaxis and endoscopic treatment, the risk of bleeding seems comparable between patients with splanchnic vein thrombosis receiving anticoagulant treatment and those who are left untreated.14.Senzolo M. Sartori M.T. Rossetto V. et al.Prospective evaluation of anticoagulation and transjugular intrahepatic portosystemic shunt for the management of portal vein thrombosis in cirrhosis.Liver Int. 2012; 32: 919-927Crossref PubMed Scopus (228) Google Scholar Endoscopic band ligation may require multiple attempts, which could delay the start of anticoagulation. Preliminary data suggest that commencing anticoagulation within 2 weeks after variceal band ligation may still achieve significant vein recanalization without increasing the incidence and severity of bleeding nor affecting the efficacy of variceal eradication.14.Senzolo M. Sartori M.T. Rossetto V. et al.Prospective evaluation of anticoagulation and transjugular intrahepatic portosystemic shunt for the management of portal vein thrombosis in cirrhosis.Liver Int. 2012; 32: 919-927Crossref PubMed Scopus (228) Google Scholar, 15.Guillaume M. Christol C. Plessier A. et al.Bleeding risk of variceal band ligation in extrahepatic portal vein obstruction is not increased by oral anticoagulation.Eur J Gastroenterol Hepatol. 2018; 30: 563-568Crossref PubMed Scopus (12) Google Scholar, 16.Plessier A. Darwish‐Murad S. Hernandez‐Guerra M. et al.Acute portal vein thrombosis unrelated to cirrhosis: a prospective multicenter follow‐up study.Hepatology. 2010; 51: 210-218Crossref PubMed Scopus (349) Google Scholar Based on currently available evidence, a suggested approach to manage patients with splanchnic vein thrombosis is outlined in Figure 1. The panel acknowledges that the available evidence on the management of splanchnic vein thrombosis is mainly derived from observational studies and, therefore, the level of evidence should be considered weak for all recommendations. Acute splanchnic vein thrombosis is generally defined as thrombosis involving one or more splanchnic veins without evidence of portal cavernoma or collateral portosystemic circulation.2.Valeriani E. Riva N. Di Nisio M. Ageno W. Splanchnic vein thrombosis: current perspectives.Vasc Health Risk Manag. 2019; 15: 449-461Crossref PubMed Scopus (40) Google Scholar Treatment of occlusive or non‐occlusive acute splanchnic vein thrombosis aims to prevent intestinal infarction or ischemia, and achieve the highest possible vessel recanalization to reduce splanchnic hypertension and bleeding risk.17.Licata A. Mazzola A. Ingrassia D. Calvaruso V. Cammà C. Craxì A. Clinical implications of the hyperdynamic syndrome in cirrhosis.Eur J Intern Med. 2014; 25: 795-802Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar Most data on the treatment of acute splanchnic vein thrombosis come from studies on patients with liver cirrhosis. In a recent trial of 65 cirrhotic patients with portal vein thrombosis receiving 6‐month therapeutic dose low molecular weight heparin (LMWH), 78.5% achieved complete (26.2%) or partial (52.3%) recanalization, 9.2% had thrombosis progression, and none experienced variceal bleeding.12.Cui S.B. Shu R.H. Yan S.P. et al.Efficacy and safety of anticoagulation therapy with different doses of enoxaparin for portal vein thrombosis in cirrhotic patients with hepatitis B.Eur J Gastroenterol Hepatol. 2015; 27: 914-919Crossref PubMed Scopus (61) Google Scholar Similar recanalization rates were reported in two prospective cohorts of cirrhotic patients of whom most had an acute or progression of a previous splanchnic vein thrombosis.10.Delgado M.G. Seijo S. Yepes I. et al.Efficacy and safety of anticoagulation on patients with cirrhosis and portal vein thrombosis.Clin Gastroenterol Hepatol. 2012; 10: 776-783Abstract Full Text Full Text PDF PubMed Scopus (250) Google Scholar, 18.Kwon J. Koh Y. Yu S.J. Yoon J.H. Low‐molecular‐weight heparin treatment for portal vein thrombosis in liver cirrhosis: efficacy and the risk of hemorrhagic complications.Thromb Res. 2018; 163: 71-76Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar In a randomized controlled trial of 80 cirrhotic patients with portal vein thrombosis after splenectomy, rivaroxaban (10 mg bid) was compared with warfarin (therapeutic range, international normalized ratio [INR] 2.0‐2.5).19.Hanafy A.S. Abd‐Elsalam S. Dawoud M.M. Randomized controlled trial of rivaroxaban versus warfarin in the management of acute non‐neoplastic portal vein thrombosis.Vascul Pharmacol. 2019; 113: 86-91Crossref PubMed Scopus (99) Google Scholar Rivaroxaban was associated with higher complete (85.0% versus 45.0%) or partial (15.0% versus 0%) recanalization rates. In addition, recurrent portal vein thrombosis after treatment discontinuation and major bleeding occurred only in warfarin‐treated patients (10.0% and 42.5%, respectively).19.Hanafy A.S. Abd‐Elsalam S. Dawoud M.M. Randomized controlled trial of rivaroxaban versus warfarin in the management of acute non‐neoplastic portal vein thrombosis.Vascul Pharmacol. 2019; 113: 86-91Crossref PubMed Scopus (99) Google Scholar These findings, however, need to be interpreted with caution due to the small size of the study, risk of bias, and the potential for residual confounding. The evidence on the treatment of acute splanchnic vein thrombosis in patients without liver cirrhosis is sparse. In a prospective cohort of 95 patients with splanchnic vein thrombosis unprovoked or secondary to myeloproliferative neoplasm or thrombophilia, treatment with vitamin K antagonists (VKAs) achieved vein recanalization in 38%, 54%, and 61% of patients with portal, mesenteric, and splenic vein thrombosis, respectively.16.Plessier A. Darwish‐Murad S. Hernandez‐Guerra M. et al.Acute portal vein thrombosis unrelated to cirrhosis: a prospective multicenter follow‐up study.Hepatology. 2010; 51: 210-218Crossref PubMed Scopus (349) Google Scholar Bleeding requiring blood transfusion or hospital admission developed in 5.3%.16.Plessier A. Darwish‐Murad S. Hernandez‐Guerra M. et al.Acute portal vein thrombosis unrelated to cirrhosis: a prospective multicenter follow‐up study.Hepatology. 2010; 51: 210-218Crossref PubMed Scopus (349) Google Scholar Use of anticoagulant therapy for longer than 6 months seemed to further improve vein recanalization in patients with mesenteric or splenic thrombosis, but not in those with portal vein thrombosis. In a retrospective study of 375 patients with acute splanchnic vein thrombosis and various underlying risk factors, the incidence of recurrent VTE (0.77 per 100 patient‐year) and major bleeding (1.24 per 100 patient‐year) was low during a median 2‐year treatment with VKAs.20.Riva N. Ageno W. Poli D. et al.Safety of vitamin K antagonist treatment for splanchnic vein thrombosis: a multicenter cohort study.J Thromb Haemost. 2015; 13: 1019-1027Crossref PubMed Scopus (24) Google Scholar Higher rates of thrombotic events (5.6 per 100 patients‐year) and major bleeding (3.9 per 100 patient‐year) were reported during treatment in a large prospective registry of 604 patients with recent splanchnic vein thrombosis of whom 77.0% received anticoagulant therapy.7.Ageno W. Riva N. Schulman S. et al.Long‐term clinical outcomes of splanchnic vein thrombosis: results of an international registry.JAMA Intern Med. 2015; 175: 1474-1480Crossref PubMed Scopus (132) Google Scholar The large variation in the rates of thrombotic or bleeding complications observed across studies may be related to differences in anticoagulant regimens, management of VKAs, outcome definitions, or characteristics of study populations. High recanalization rates with anticoagulation have been observed also for acute splanchnic vein thrombosis secondary to abdominal inflammation or infection, inflammatory bowel disease, or general or bariatric surgery.21.Rottenstreich A. Kleinstern G. Spectre G. Da'as N. Ziv E. Kalish Y. Thromboembolic events following splenectomy: risk factors, prevention, management and outcomes.World J Surg. 2018; 42: 675-681Crossref PubMed Scopus (23) Google Scholar, 22.Rottenstreich A. Elazary R. Kalish Y. Abdominal thrombotic complications following bariatric surgery.Surg Obes Relat Dis. 2017; 13: 78-84Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar, 23.Kanellopoulou T. Alexopoulou A. Theodossiades G. Koskinas J. Archimandritis A.J. Pylephlebitis: an overview of non‐cirrhotic cases and factors related to outcome.Scand J Infect Dis. 2010; 42: 804-811Crossref PubMed Scopus (75) Google Scholar, 24.Landman C. Nahon S. Cosnes J. et al.Portomesenteric vein thrombosis in patients with inflammatory bowel disease.Inflamm Bowel Dis. 2013; 19: 582-589Crossref PubMed Scopus (28) Google Scholar The role of systemic or catheter‐directed thrombolysis has been evaluated only in small case‐series which reported promising results mostly in terms of vein recanalization, but a high risk of major and fatal bleeding.25.Smalberg J.H. Spaander M.V. Jie K.S. et al.Risks and benefits of transcatheter thrombolytic therapy in patients with splanchnic venous thrombosis.Thromb Haemost. 2008; 100: 1084-1088Crossref PubMed Google Scholar, 26.Hollingshead M. Burke C.T. Mauro M.A. Weeks S.M. Dixon R.G. Jaques P.F. Transcatheter thrombolytic therapy for acute mesenteric and portal vein thrombosis.J Vasc Interv Radiol. 2005; 16: 651-661Abstract Full Text Full Text PDF PubMed Scopus (223) Google Scholar, 27.Kim H.S. Patra A. Khan J. Arepally A. Streiff M.B. Transhepatic catheter‐directed thrombectomy and thrombolysis of acute superior mesenteric venous thrombosis.J Vasc Interv Radiol. 2005; 16: 1685-1691Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar, 28.Sharma S. Texeira A. Texeira P. Elias E. Wilde J. Olliff S.P. Pharmacological thrombolysis in Budd Chiari syndrome: a single centre experience and review of the literature.J Hepatol. 2004; 40: 172-180Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar, 29.Yang S. Zhang L. Liu K. et al.Postoperative catheter‐directed thrombolysis versus systemic anticoagulation for acute superior mesenteric venous thrombosis.Ann Vasc Surg. 2016; 35: 88-97Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar Based on these preliminary observations, thrombolysis may be carefully evaluated in specialized centers for very selected patients such as those with clinical deterioration despite anticoagulant therapy. Because specific treatment for splanchnic vein thrombosis was not mandatory in most studies, the choice of anticoagulant agent and intensity of anticoagulation have been highly heterogeneous. LMWH either alone or in combination with VKAs was evaluated in observational studies that were often small, retrospective, and with a high risk of bias.2.Valeriani E. Riva N. Di Nisio M. Ageno W. Splanchnic vein thrombosis: current perspectives.Vasc Health Risk Manag. 2019; 15: 449-461Crossref PubMed Scopus (40) Google Scholar, 30.Ageno W. Riva N. Schulman S. et al.Antithrombotic treatment of splanchnic vein thrombosis: results of an international registry.Semin Thromb Hemost. 2014; 40: 99-105PubMed Google Scholar The evidence on oral anticoagulants directly inhibiting thrombin (dabigatran) or activated factor X (rivaroxaban, apixaban, and edoxaban) is very limited. Direct oral anticoagulants (DOACs) have shown similar efficacy and better safety compared with VKAs in patients with usual site acute VTE and are the current recommended first line treatment. A similarly favorable risk‐benefit profile of DOACs may be expected in patients with splanchnic vein thrombosis. In contrast with LMWH or VKAs, DOACs may have a pronounced first‐pass effect that could result in high concentrations of these agents at site of splanchnic vein thrombosis with standard concentrations in the periphery. The potential for DOACs malabsorption needs to be considered in cases complicated by bowel ischemia. The type and dose of anticoagulant treatment may need frequent adjustments according to a number of patient comorbidities such as low platelet count, and liver and renal impairment.2.Valeriani E. Riva N. Di Nisio M. Ageno W. Splanchnic vein thrombosis: current perspectives.Vasc Health Risk Manag. 2019; 15: 449-461Crossref PubMed Scopus (40) Google Scholar LMWH alone may be preferable in patients with moderate to severe impairment of liver function as the latter may negatively affect the quality of anticoagulation with VKAs. The use of DOACs is contraindicated in case of moderate (rivaroxaban) or severe (all DOACs) liver dysfunction. In most countries, the use of DOACs remains off‐label in patients with splanchnic vein thrombosis regardless of the presence of cirrhosis. Another advantage of LMWH is the possibility to adapt doses in patients with thrombocytopenia or recent bleeding. LMWH has shown better efficacy and similar safety compared with VKAs in patients with cancer and VTE, and their use may be considered in cases of splanchnic vein thrombosis and underlying malignancy.31.Key N.S. Khorana A.A. Kuderer N.M. et al.Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO Clinical Practice Guideline Update.J Clin Oncol. 2019; 38: 496-520Crossref PubMed Scopus (651) Google Scholar In patients with gastrointestinal cancer, the use of DOACs (edoxaban and rivaroxaban) was associated with increased risk of gastrointestinal bleeding compared with LMWH. The Scientific and Standardization Committee (SSC) guidance of the International Society on Thrombosis and Haemostasis (ISTH) suggests treatment with LMWH in cancer patients with VTE who have luminal gastrointestinal malignancy, active gastrointestinal mucosal abnormalities, genitourinary cancer at high risk of bleeding, or are receiving systemic therapy with potential drug‐drug interactions with DOACs.32.Khorana A.A. Noble S. Lee A.Y.Y. et al.Role of direct oral anticoagulants in the treatment of cancer‐associated venous thromboembolism: guidance from the SSC of the ISTH.J Thromb Haemost. 2018; 16: 1891-1894Crossref PubMed Scopus (245) Google Scholar The optimal duration of anticoagulant treatment for splanchnic vein thrombosis remains unclear. Most studies have provided anticoagulation for 6 months or longer.7.Ageno W. Riva N. Schulman S. et al.Long‐term clinical outcomes of splanchnic vein thrombosis: results of an international registry.JAMA Intern Med. 2015; 175: 1474-1480Crossref PubMed Scopus (132) Google Scholar, 10.Delgado M.G. Seijo S. Yepes I. et al.Efficacy and safety of anticoagulation on patients with cirrhosis and portal vein thrombosis.Clin Gastroenterol Hepatol. 2012; 10: 776-783Abstract Full Text Full Text PDF PubMed Scopus (250) Google Scholar, 12.Cui S.B. Shu R.H. Yan S.P. et al.Efficacy and safety of anticoagulation therapy with different doses of enoxaparin for portal vein thrombosis in cirrhotic patients with hepatitis B.Eur J Gastroenterol Hepatol. 2015; 27: 914-919Crossref PubMed Scopus (61) Google Scholar, 14.Senzolo M. Sartori M.T. Rossetto V. et al.Prospective evaluation of anticoagulation and transjugular intrahepatic portosystemic shunt for the management of portal vein thrombosis in cirrhosis.Liver Int. 2012; 32: 919-927Crossref PubMed Scopus (228) Google Scholar, 18.Kwon J. Koh Y. Yu S.J. Yoon J.H. Low‐molecular‐weight heparin treatment for portal vein thrombosis in liver cirrhosis: efficacy and the risk of hemorrhagic complications.Thromb Res. 2018; 163: 71-76Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 19.Hanafy A.S. Abd‐Elsalam S. Dawoud M.M. Randomized controlled trial of rivaroxaban versus warfarin in the management of acute non‐neoplastic portal vein thrombosis.Vascul Pharmacol. 2019; 113: 86-91Crossref PubMed Scopus (99) Google Scholar, 20.Riva N. Ageno W. Poli D. et al.Safety of vitamin K antagonist treatment for splanchnic vein thrombosis: a multicenter cohort study.J Thromb Haemost. 2015; 13: 1019-1027Crossref PubMed Scopus (24) Google Scholar Extended treatment duration beyond 6 months may be beneficial in subgroups at high risk such as those awaiting liver transplantation with the aim of lowering the risk of vein thrombosis recurrence or progression.10.Delgado M.G. Seijo S. Yepes I. et al.Efficacy and safety of anticoagulation on patients with cirrhosis and portal vein thrombosis.Clin Gastroenterol Hepatol. 2012; 10: 776-783Abstract Full Text Full Text PDF PubMed Scopus (250) Google Scholar, 18.Kwon J. Koh Y. Yu S.J. Yoon J.H. Low‐molecular‐weight heparin treatment for portal vein thrombosis in liver cirrhosis: efficacy and the risk of hemorrhagic complications.Thromb Res. 2018; 163: 71-76Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 20.Riva N. Ageno W. Poli D. et al.Safety of vitamin K antagonist treatment for splanchnic vein thrombosis: a multicenter cohort study.J Thromb Haemost. 2015; 13: 1019-1027Crossref PubMed Scopus (24) Google Scholar, 33.Amitrano L. Guardascione M.A. Menchise A. et al.Safety and efficacy of anticoagulation therapy with low molecular weight heparin for portal vein thrombosis in patients with liver cirrhosis.J Clin Gastroenterol. 2010; 44: 448-451Crossref PubMed Scopus (238) Google Scholar Other patient groups who may benefit from longer anticoagulation include those with history of intestinal ischemia; thrombosis extending beyond the portal vein; thrombosis recurrence or progression after treatment discontinuation; unprovoked thrombosis; or thrombosis associated with a persistent risk factor, such as severe inherited thrombophilia or myeloproliferative neoplasms.7.Ageno W. Riva N. Schulman S. et al.Long‐term clinical outcomes of splanchnic vein thrombosis: results of an international registry.JAMA Intern Med. 2015; 175: 1474-1480Crossref PubMed Scopus (132) Google Scholar, 10.Delgado M.G. Seijo S. Yepes I. et al.Efficacy and safety of anticoagulation on patients with cirrhosis and portal vein thrombosis.Clin Gastroenterol Hepatol. 2012; 10: 776-783Abstract Full Text Full Text PDF PubMed Scopus (250) Google Scholar, 16.Plessier A. Darwish‐Murad S. Hernandez‐Guerra M. et al.Acute portal vein thrombosis unrelated to cirrhosis: a prospective multicenter follow‐up study.Hepatology. 2010; 51: 210-218Crossref PubMed Scopus (349) Google Scholar, 18.Kwon J. Koh Y. Yu S.J. Yoon J.H. Low‐molecular‐weight heparin treatment for portal vein thrombosis in liver cirrhosis: efficacy and the risk of hemorrhagic complications.Thromb Res. 2018; 163: 71-76Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 19.Hanafy A.S. Abd‐Elsalam S. Dawoud M.M. Randomized controlled trial of rivaroxaban versus warfarin in the management of acute non‐neoplastic portal vein thrombosis.Vascul Pharmacol. 2019; 113: 86-91Crossref PubMed Scopus (99) Google Scholar, 34.Amitrano L. Guardascione M.A. Scaglione M. et al.Splanchnic vein thrombosis and variceal rebleeding in patients with cirrhosis.Eur J Gastroenterol Hepatol. 2012; 24: 1381-1385Crossref PubMed Scopus (31) Google Scholar In this latter case, cytoreduction appeared not to reduce recurrent thrombosis.35.Sant'Antonio E. Guglielmelli P. Pieri L. et al.Splanchnic vein thromboses associated with myeloproliferative neoplasms: an international, retrospective study on 518 cases.Am J Hematol. 2020; 95: 156-166Crossref PubMed Scopus (31) Google Scholar The evidence to guide anticoagulant treatment duration based on the rate of vein recanalization remains limited.14.Senzolo M. Sartori M.T. Rossetto V. et al.Prospective evaluation of anticoagulation and transjugular intrahepatic portosystemic shunt for the management of portal vein thrombosis in cirrhosis.Liver Int. 2012; 32: 919-927Crossref PubMed Scopus (228) Google Scholar, 18.Kwon J. Koh Y. Yu S.J. Yoon J.H. Low‐molecular‐weight heparin treatment for portal vein thrombosis in liver cirrhosis: efficacy and the risk of hemorrhagic complications.Thromb Res. 2018; 163: 71-76Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 19.Hanafy A.S. Abd‐Elsalam S. Dawoud M.M. Randomized controlled trial of rivaroxaban versus warfarin in the management of acute non‐neoplastic portal vein thrombosis.Vascul Pharmacol. 2019; 113: 86-91Crossref PubMed Scopus (99) Google Scholar Chronic splanchnic vein thrombosis is generally defined by the presence of signs of long‐standing thrombosis such as extensive intra‐abdominal venous collaterals or cavernous transformation of the portal vein.2.Valeriani E. Riva N. Di Nisio M. Ageno W. Splanchnic vein thrombosis: current perspectives.Vasc Health Risk Manag. 2019; 15: 449-461Crossref PubMed Scopus (40) Google Scholar The age of the thrombus can only be approximated by the clinical course of symptoms or the time interval between the first imaging procedure demonstrating splanchnic vein thrombosis and previous radiological imaging with no signs of thrombosis, if available.14.Senzolo M. Sartori M.T. Rossetto V. et al.Prospective evaluation of anticoagulation and transjugular intrahepatic portosystemic shunt for the management of portal vein thrombosis in cirrh