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Incidence and factors predictive of recurrent thrombosis in people with non-cirrhotic portal vein thrombosis

  • Author Footnotes
    † Shared first authorship: Anna Baiges, Bogdan Procopet, and Gilberto Silva-Junior.
    Anna Baiges
    Correspondence
    Corresponding authors. Address: Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Clínic, Villarroel 170, Barcelona 08036, Spain. Tel.: +34-93-2275753.
    Footnotes
    † Shared first authorship: Anna Baiges, Bogdan Procopet, and Gilberto Silva-Junior.
    Affiliations
    Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain (Health Care Provider of the ERN-Liver)

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
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  • Author Footnotes
    † Shared first authorship: Anna Baiges, Bogdan Procopet, and Gilberto Silva-Junior.
    Bogdan Procopet
    Footnotes
    † Shared first authorship: Anna Baiges, Bogdan Procopet, and Gilberto Silva-Junior.
    Affiliations
    Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain (Health Care Provider of the ERN-Liver)

    University of Medicine and Pharmacy ‘Iuliu Hatieganu’, 3rd Medical Clinic, Regional Institute of Gastroenterology and Hepatology ‘O. Fodor’, Gastroenterology Department, Cluj-Napoca, Romania
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  • Author Footnotes
    † Shared first authorship: Anna Baiges, Bogdan Procopet, and Gilberto Silva-Junior.
    Gilberto Silva-Junior
    Footnotes
    † Shared first authorship: Anna Baiges, Bogdan Procopet, and Gilberto Silva-Junior.
    Affiliations
    Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain (Health Care Provider of the ERN-Liver)
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  • Elba Llop
    Affiliations
    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain

    Gastroenterology and Hepatology Service, Hospital Universitario de Puerta de Hierro-Majadahonda, Universidad Autónoma de Madrid, Madrid, Spain
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  • Luis Tellez
    Affiliations
    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain

    Department of Gastroenterology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria, University of Alcalá, Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
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  • Anna Darnell
    Affiliations
    Centre de Diagnostic per l’Imatge, Hospital Clínic, Barcelona, Spain
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  • Ángeles Garcia-Criado
    Affiliations
    Centre de Diagnostic per l’Imatge, Hospital Clínic, Barcelona, Spain
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  • Fanny Turon
    Affiliations
    Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain (Health Care Provider of the ERN-Liver)

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
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  • Oana Nicoara-Farcau
    Affiliations
    Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain (Health Care Provider of the ERN-Liver)

    University of Medicine and Pharmacy ‘Iuliu Hatieganu’, 3rd Medical Clinic, Regional Institute of Gastroenterology and Hepatology ‘O. Fodor’, Gastroenterology Department, Cluj-Napoca, Romania
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  • Carlos González-Alayón
    Affiliations
    Liver Unit, Hospital Universitario de Canarias (HUC), La Laguna, Spain
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  • Hélène Larrue
    Affiliations
    Service d'Hépatologie, Hôpital Rangueil, Fédération Hospitalo-Universitaire IMPACT, CHU de Toulouse, et Université Toulouse 3 – Paul Sabatier, Toulouse, France
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  • Marta Magaz
    Affiliations
    Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain (Health Care Provider of the ERN-Liver)
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  • Pol Olivas
    Affiliations
    Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain (Health Care Provider of the ERN-Liver)
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  • Valeria Perez-Campuzano
    Affiliations
    Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain (Health Care Provider of the ERN-Liver)
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  • Jose Luis Calleja
    Affiliations
    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain

    Gastroenterology and Hepatology Service, Hospital Universitario de Puerta de Hierro-Majadahonda, Universidad Autónoma de Madrid, Madrid, Spain
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  • Agustin Albillos
    Affiliations
    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain

    Department of Gastroenterology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria, University of Alcalá, Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
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  • Juan Carlos Reverter
    Affiliations
    Hemotherapy and Hemostasis Department, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
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  • Christophe Bureau
    Affiliations
    Service d'Hépatologie, Hôpital Rangueil, Fédération Hospitalo-Universitaire IMPACT, CHU de Toulouse, et Université Toulouse 3 – Paul Sabatier, Toulouse, France
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  • Jaime Bosch
    Affiliations
    Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain (Health Care Provider of the ERN-Liver)

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain

    Hepatology, University Clinic for Visceral Surgery and Medicine, Inselspital, Bern University, Bern, Switzerland
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  • Virginia Hernández-Gea
    Affiliations
    Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain (Health Care Provider of the ERN-Liver)

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
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  • Juan Carlos Garcia-Pagán
    Correspondence
    Corresponding authors. Address: Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Clínic, Villarroel 170, Barcelona 08036, Spain. Tel.: +34-93-2275753.
    Affiliations
    Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain (Health Care Provider of the ERN-Liver)

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
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  • on behalf ofREHEVASC
    Author Footnotes
    ‡ REHEVASC, Registro Español de Enfermedades Hepáticas Vasculares.
  • VALDIG
    Author Footnotes
    § VALDIG, Vascular Liver Diseases Interest Group.
  • an EASL consortium
  • Author Footnotes
    † Shared first authorship: Anna Baiges, Bogdan Procopet, and Gilberto Silva-Junior.
    ‡ REHEVASC, Registro Español de Enfermedades Hepáticas Vasculares.
    § VALDIG, Vascular Liver Diseases Interest Group.
Published:September 01, 2022DOI:https://doi.org/10.1016/j.jhep.2022.08.023

      Highlights

      • Individuals with non-cirrhotic splanchnic thrombosis without thrombophilia are at risk of re-thrombosis.
      • Splanchnic re-thrombosis can be asymptomatic and requires screening for its detection.
      • Factor VIII ≥150% may help identify individuals at higher risk of re-thrombosis.

      Background & Aims

      Clinical guidelines do not recommend long-term anticoagulation in non-cirrhotic splanchnic vein thrombosis (NC-SVT) without underlying thrombophilia because it is assumed that there is a very low risk of recurrent thrombosis (RT). Our first aim was to describe the incidence of RT in people with NC-SVT without an indication for long-term anticoagulation. The second aim was to identify RT risk factors and afterwards verify them in a validation cohort.

      Methods

      This is a multicentre, retrospective observational study evaluating risk factors for RT in 64 people with NC-SVT of idiopathic/local factor aetiology. In a subgroup of 48 individuals, the potential value of additional thrombophilic parameters to predict RT was analysed. Findings were validated in 70 individuals with idiopathic/local factor NC-SVT.

      Results

      Of the 64 participants in the training cohort, 17 (26%) presented splanchnic and/or extrasplanchnic RT (overall-RT) during follow-up (cumulative incidence: 2, 10, 19, and 34% at 1, 2, 5, and 10 years, respectively). In addition, 53% of people with splanchnic RT were asymptomatic. No clinical or biochemical parameters predicted overall-RT. However, in the 48 people with an additional comprehensive thrombophilic study, factor VIII ≥150% was the only independent factor predicting overall-RT (hazard ratio 7.10, 95% CI 2.17–23.17, p <0.01). In the validation cohort, 19 individuals (27%) presented overall-RT, and it was also independently predicted by factor VIII >150% (hazard ratio 3.71, 95% CI 1.31–10.5, p <0.01). The predictive value of factor VIII was confirmed in both people with idiopathic/local factor aetiology associated NC-SVT.

      Conclusions

      People with idiopathic/local factor NC-SVT are at risk of overall-RT. Splanchnic RT can be asymptomatic and requires screening for its detection. Values of factor VIII ≥150% may help identify individuals at high risk of overall-RT who could benefit from long-term anticoagulation.

      Impact and implications

      People with idiopathic/isolated local factor non-cirrhotic portal vein thrombosis were previously thought to be at minimal risk of re-thrombosis and therefore did not receive scheduled follow-up. The results of this study are of special interest for hepatologists treating people with non-cirrhotic splanchnic thrombosis, as they show a 25% incidence of re-thrombosis and support the close follow-up of people with factor VIII >150% to ensure the early identification of new thrombotic events.

      Graphical abstract

      Keywords

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      References

        • Garcia-Pagán J.C.
        • Hernández-Guerra M.
        • Bosch J.
        Extrahepatic portal vein thrombosis.
        Semin Liver Dis. 2008; 1: 282-292
        • Baiges A.
        • Morena-Barrio M.E.
        • Turon F.
        • Miñano A.
        • Alberto Ferrusquía J.
        • Magaz M.
        • et al.
        Congenital antithrombin deficiency in patients with splanchnic vein thrombosis.
        Liver Int. 2020; 40: 1168-1177
        • Turon F.
        • Cervantes F.
        • Colomer D.
        • Baiges A.
        • Hernández-Gea V.
        • Garcia-Pagán J.C.
        Role of calreticulin mutations in the aetiological diagnosis of splanchnic vein thrombosis.
        J Hepatol. 2015; 62: 72-74
        • Magaz M.
        • Alvarez-Larrán A.
        • Colomer D.
        • López-Guerra M.
        • García-Criado M.Á.
        • Mezzano G.
        • et al.
        Next-generation sequencing in the diagnosis of non-cirrhotic splanchnic vein thrombosis.
        J Hepatol. 2021; 74: 89-95
        • Amitrano L.
        • Guardascione M.A.
        • Scaglione M.
        • Pezzullo L.
        • Sangiuliano N.
        • Armellino M.F.
        • et al.
        Prognostic factors in noncirrhotic patients with splanchnic vein thromboses.
        Am J Gastroenterol. 2007; 102: 2464-2470
        • Condat B.
        • Pessione F.
        • Hillaire S.
        • Denninger M.H.
        • Guillin M.C.
        • Poliquin M.
        • et al.
        Current outcome of portal vein thrombosis in adults: risk and benefit of anticoagulant therapy.
        Gastroenterology. 2001; 120: 490-497
        • Spaander M.C.W.
        • Hoekstra J.
        • Hansen B.E.
        • Van Buuren H.R.
        • Leebeek F.W.G.
        • Janssen H.L.A.
        Anticoagulant therapy in patients with non-cirrhotic portal vein thrombosis: effect on new thrombotic events and gastrointestinal bleeding.
        J Thromb Haemost. 2013; 11: 452-459
        • Garcia-Pagán J.C.
        • Buscarini E.
        • Janssen H.L.A.
        • Leebeek F.W.G.
        • Plessier A.
        • Rubbia-Brandt L.
        • et al.
        EASL Clinical Practice Guidelines: vascular diseases of the liver.
        J Hepatol. 2016; 64: 179-202
        • de Franchis R.
        • on behalf of the Baveno VI Faculty
        Expanding consensus in portal hypertension. Report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension.
        J Hepatol. 2015; 63: 743-752
        • de Franchis R.
        • Bosch J.
        • Garcia-Tsao G.
        • Reiberger T.
        • Ripoll C.
        • Baveno VII Faculty
        Baveno VII – renewing consensus in portal hypertension.
        J Hepatol. 2022; 76: 959-974
        • Raffa S.
        • Reverter J.C.
        • Seijo S.
        • Tassies D.
        • Abraldes J.G.
        • Bosch J.
        • et al.
        Hypercoagulability in patients with chronic noncirrhotic portal vein thrombosis.
        Clin Gastroenterol Hepatol. 2012; 10: 72-78
        • de Raucourt E.
        • Kuadjovi C.
        • Rautou P.E.
        • Ajzenberg N.
        • Boudaoud L.
        • Valla D.
        • et al.
        Thrombin generation in patients with non-cirrhotic vascular liver diseases treated or not treated with vitamin K antagonist.
        Thromb Res. 2017; 155: 28-30
        • Martinelli I.
        • Primignani M.
        • Aghemo A.
        • Reati R.
        • Bucciarelli P.
        • Fabris F.
        • et al.
        High levels of factor VIII and risk of extra-hepatic portal vein obstruction.
        J Hepatol. 2009; 50: 916-922
        • Kyrle P.A.
        • Minar E.
        • Hirschl M.
        • Bialonczyk C.
        • Stain M.
        • Schneider B.
        • et al.
        High plasma levels of factor VIII and the risk of recurrent venous thromboembolism.
        N Engl J Med. 2000; 343: 457-462
        • Timp J.F.
        • Lijfering W.M.
        • Flinterman L.E.
        • van Hylckama Vlieg A.
        • le Cessie S.
        • Rosendaal F.R.
        • et al.
        Predictive value of factor VIII levels for recurrent venous thrombosis: results from the MEGA follow-up study.
        J Thromb Haemost. 2015; 13: 1823-1832
        • Martinelli I.
        von Willebrand factor and factor VIII as risk factors for arterial and venous thrombosis.
        Semin Hematol. 2005; 42: 49-55
        • Koster T.
        • Blann A.D.
        • Briët E.
        • Vandenbroucke J.P.
        • Rosendaal F.R.
        Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis.
        Lancet. 1995; 345: 152-155
        • De Stefano V.
        • Ruggeri M.
        • Cervantes F.
        • Alvarez-Larrán A.
        • Iurlo A.
        • Randi M.L.
        • et al.
        High rate of recurrent venous thromboembolism in patients with myeloproliferative neoplasms and effect of prophylaxis with vitamin K antagonists.
        Leukemia. 2016; 30: 2032-2038
        • Plessier A.
        • Goria O.
        • Al E.
        Prophylaxis of recurrent thrombosis by rivaroxaban in patients with non-cirrhotic portal vein thrombosis a multicentre randomized controlled study testing rivaroxaban vs no anticoagulation.
        J Hepatol. 2021; 75: S191-S865
        • Kraaijenhagen R.A.
        • in’t Anker P.S.
        • Koopman M.M.
        • Reitsma P.H.
        • Prins M.H.
        • van den Ende A.
        • et al.
        High plasma concentration of factor VIIIc is a major risk factor for venous thromboembolism.
        Thromb Haemost. 2000; 83: 5-9
        • Cosmi B.
        • Legnani C.
        • Cini M.
        • Favaretto E.
        • Palareti G.
        D-dimer and factor VIII are independent risk factors for recurrence after anticoagulation withdrawal for a first idiopathic deep vein thrombosis.
        Thromb Res. 2008; 122: 610-617
        • Cristina L.
        • Benilde C.
        • Michela C.
        • Mirella F.
        • Giuliana G.
        • Gualtiero P.
        High plasma levels of factor VIII and risk of recurrence of venous thromboembolism.
        Br J Haematol. 2004; 124: 504-510
        • Hoekstra J.
        • Bresser E.L.
        • Smalberg J.H.
        • Spaander M.C.W.
        • Leebeek F.W.G.
        • Janssen H.L.A.
        Long-term follow-up of patients with portal vein thrombosis and myeloproliferative neoplasms.
        J Thromb Haemost. 2011; 9: 2208-2214