Anticoagulation in Cirrhosis and Portal Vein Thrombosis Is Safe and Improves Prognosis in Advanced Cirrhosis

  • Carlos Noronha FerreiraEmail author
  • Daniela Reis
  • Helena Cortez-Pinto
  • Rui Tato Marinho
  • Afonso Gonçalves
  • Sónia Palma
  • Inês Leite
  • Tiago Rodrigues
  • Ana Júlia Pedro
  • Paula Alexandrino
  • Fátima Serejo
  • Margarida Sobral Dias
  • Paula Ferreira
  • Mariana Vasconcelos
  • Filipe Damião
  • Leonor Xavier Brito
  • Cilenia Baldaia
  • Narcisa Fatela
  • Fernando Ramalho
  • José Velosa
Original Article



The role of portal vein thrombosis (PVT) in the natural history of cirrhosis is controversial.


We analyzed the safety and effect of anticoagulant therapy (AT) on PVT recanalization and orthotopic liver transplant (OLT)-free survival.


Eighty consecutive patients from a prospective registry of cirrhosis and non-tumoral PVT at a tertiary center were analyzed. AT effect on PVT recanalization and OLT-free survival was determined by time-dependent Cox regression analysis.


Average MELD score was 15 ± 7. Portal hypertension-related complications at PVT diagnosis were present in 65 (81.3%) patients. Isolated portal vein trunk/branch thrombosis was present in 53 (66.3%) patients. AT was started in 37 patients. AT was stopped in 17 (45.9%) patients, in 4 (10.8%) due to bleeding events. No variceal bleeding occurred while on AT. Anticoagulation was restarted in 6/17 (35.2%) patients due to rethrombosis. In 67 patients with adequate follow-up imaging, AT significantly increased the rate of PVT recanalization compared with those who did not receive anticoagulation [51.4% (18/35) vs 6/32 (18.8%), p = 0.005]. OLT-free survival after a median follow-up of 25 (1–146) months was 32 (40%). Although there was no significant effect of AT on overall OLT-free survival, OLT-free survival was higher among patients with MELD ≥ 15 receiving AT compared to those who did not (p = 0.011). Baseline MELD at PVT detection independently predicted PVT recanalization (HR 1.11, 95% CI 1.01–1.21, p = 0.027) and mortality/OLT (HR 1.12, 95% CI 1.05–1.19, p < 0.001).


Although AT did not improve overall OLT-free survival, it was associated with higher survival in advanced cirrhosis. Anticoagulation increased PVT recanalization and should be maintained after PVT recanalization to avoid rethrombosis.


Portal vein thrombosis Cirrhosis Anticoagulation Rethrombosis Orthotopic liver transplantation Prognosis 



Portal vein thrombosis




Orthotopic liver transplantation


Low molecular weight heparin


Anticoagulant therapy


Hepatocellular carcinoma


Computerized tomography


Magnetic resonance imaging


Transjugular intrahepatic portosystemic shunt




Model for End-Stage Liver Disease


Gastroesophageal varices type 1


Isolated gastric varices


Gastroesophageal varices type 2


Upper gastrointestinal bleeding



We would like to express our sincere thanks to Professors Dominique Valla and Juan Carlos García-Pagán for their constructive comments and expert advice in preparation of this manuscript, Dr. Teresa Rodrigues for her valuable support and advice regarding statistical analysis of this manuscript, and Drs. Filipe Calinas, Joana Saiote, and Mario Silva for their help in data collection in some patients.

Author’s contribution

Carlos Noronha Ferreira, MD, was involved in study design, patient inclusion, data collection, data analysis and preparation, and critical review of the manuscript. Daniela Reis, MD, performed data collection and critical review of the manuscript. Helena Cortez-Pinto, PhD, Rui Tato Marinho, PhD, Afonso Gonçalves, MD, Sónia Palma, MD, Inês Leite, MD, Tiago Rodrigues, MD, Ana Júlia Pedro, MD, Paula Alexandrino, MD, Fátima Serejo, PhD, Margarida Sobral Dias, MD, Paula Ferreira, MD, Mariana Vasconcelos, MD, Filipe Damião, MD, Leonor Xavier Brito, MD, Cilenia Baldaia, MD, Narcisa Fatela, MD, Fernando Ramalho, PhD, José Velosa, PhD, were all involved in patient inclusion and critical review of the manuscript.

Compliance with ethical standards

Conflict of interest

None of the authors have any conflicts of interest to declare related to the study.

Ethics standards

Individual formal consent was not required, and institutional ethics committee approval was obtained, and the study was conducted according to the 1964 Declaration of Helsinki, later amendments, or comparable ethics standards.

Supplementary material

10620_2019_5572_MOESM1_ESM.docx (242 kb)
Supplementary material 1 (DOCX 241 kb)


  1. 1.
    Tsochatzis EA, Senzolo M, Germani G, Gatt A, Burroughs AK. Systematic review: portal vein thrombosis in cirrhosis. Aliment Pharmacol Ther. 2010;31:366–374.CrossRefGoogle Scholar
  2. 2.
    Francoz C, Valla D, Durand F. Portal vein thrombosis, cirrhosis, and liver transplantation. J Hepatol. 2012;57:203–212.CrossRefGoogle Scholar
  3. 3.
    Nery F, Chevret S, Condat B, et al. Causes and consequences of portal vein thrombosis in 1243 patients with cirrhosis: results of a longitudinal study. Hepatology. 2015;61:660–667.CrossRefGoogle Scholar
  4. 4.
    Dumortier J, Czyglik O, Poncet G, et al. Eversion thrombectomy for portal vein thrombosis during liver transplantation. Am J Transpl. 2002;2:934–938.CrossRefGoogle Scholar
  5. 5.
    Lendoire J, Raffin G, Cejas N, et al. Liver transplantation in adult patients with portal vein thrombosis: risk factors, management and outcome. HPB (Oxford). 2007;9:352–356.CrossRefGoogle Scholar
  6. 6.
    Francoz C, Belghiti J, Vilgrain V, et al. Splanchnic vein thrombosis in candidates for liver transplantation: usefulness of screening and anticoagulation. Gut. 2005;54:691–697.CrossRefGoogle Scholar
  7. 7.
    Englesbe MJ, Kubus J, Muhammad W, et al. Portal vein thrombosis and survival in patients with cirrhosis. Liver Transpl. 2010;16:83–90.CrossRefGoogle Scholar
  8. 8.
    Villa E, Cammà C, Marietta M, et al. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis. Gastroenterology. 2012;143:1253–1260.e1-4.CrossRefGoogle Scholar
  9. 9.
    La Mura V, Braham S, Tosetti G, et al. Harmful and beneficial effects of anti-coagulants in patients with cirrhosis and portal vein thrombosis. Clin Gastroenterol Hepatol. 2018;16:1146–1152.CrossRefGoogle Scholar
  10. 10.
    Loffredo L, Pastori D, Farcomeni A, Violi F. Effects of anticoagulants in patients with cirrhosis and portal vein thrombosis: a systematic review and meta-analysis. Gastroenterology. 2017;45:1105–1110.Google Scholar
  11. 11.
    Pettinari I, Vukotic R, Stefanescu H, et al. Clinical impact and safety of anticoagulants for portal vein thrombosis in cirrhosis. Am J Gastroenterol. 2019;114:258–266.CrossRefGoogle Scholar
  12. 12.
    Tublin ME, Dodd GD, Baron RL. Benign and malignant portal vein thrombosis: differentiation by CT characteristics. AJR. 1997;168:719–723.CrossRefGoogle Scholar
  13. 13.
    Ageno W, Riva N, Schulman S, et al. Long-term clinical outcomes of splanchnic vein thrombosis. JAMA Intern Med. 2015;175:1474.CrossRefGoogle Scholar
  14. 14.
    Ha NB, Regal RE. Anticoagulation in patients with cirrhosis: caught between a rock-liver and a hard place. Ann Pharmacother. 2016;50:402–409.CrossRefGoogle Scholar
  15. 15.
    Englesbe MJ, Schaubel DE, Cai S, Guidinger MKMR. Portal vein thrombosis and liver transplant survival benefit. Liver Transpl. 2010;16:999–1005.CrossRefGoogle Scholar
  16. 16.
    Amitrano L, Guardascione MA, 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;44:448–451.Google Scholar
  17. 17.
    Ghabril M, Agarwal S, Lacerda M, Chalasani N, Kwo P, Joseph Tector A. Portal vein thrombosis is a risk factor for poor early outcomes after liver transplantation: analysis of risk factors and outcomes for portal vein thrombosis in waitlisted patients. Transplantation. 2016;100:126–133.CrossRefGoogle Scholar
  18. 18.
    de Franchis R. 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.CrossRefGoogle Scholar
  19. 19.
    EASL Clinical Practical Guidelines. Vascular diseases of the liver. J Hepatol. 2016;64:179–202.CrossRefGoogle Scholar
  20. 20.
    Delgado MG, Seijo S, Yepes I, et al. Efficacy and safety of anticoagulation on patients with cirrhosis and portal vein thrombosis. Clin Gastroenterol Hepatol. 2012;10:776–783.CrossRefGoogle Scholar
  21. 21.
    Ageno W, Riva N, Schulman S, et al. Antithrombotic treatment of splanchnic vein thrombosis: results of an international registry. Semin Thromb Hemost. 2014;40:99–105.Google Scholar
  22. 22.
    Cerini F, Gonzalez JM, Torres F, et al. Impact of anticoagulation on upper-gastrointestinal bleeding in cirrhosis. A retrospective multicenter study. Hepatology. 2015;62:575–583.CrossRefGoogle Scholar
  23. 23.
    Qi X, De Stefano V, Li H, Dai J, Guo X, Fan D. Anticoagulation for the treatment of portal vein thrombosis in liver cirrhosis: a systematic review and meta-analysis of observational studies. Eur J Intern Med. 2015;26:23–29.CrossRefGoogle Scholar
  24. 24.
    Kwon J, Koh Y, Jong YS, Yoon JH. Low-molecular-weight heparin treatment for portal vein thrombosis in liver cirrhosis: efficacy and the risk of hemorrhagic complications. Thromb Res. 2018;163:71–76.CrossRefGoogle Scholar
  25. 25.
    Werner KT, Sando S, Carey EJ, et al. Portal vein thrombosis in patients with end stage liver disease awaiting liver transplantation: outcome of anticoagulation. Dig Dis Sci. 2013;58:1776–1780. Scholar
  26. 26.
    De Gottardi A, Trebicka J, Klinger C, et al. Antithrombotic treatment with direct-acting oral anticoagulants in patients with splanchnic vein thrombosis and cirrhosis. Liver Int. 2017;37:694–699.CrossRefGoogle Scholar
  27. 27.
    Chen H, Liu L, Qi X, et al. Efficacy and safety of anticoagulation on more advanced portal vein thrombosis in patients with liver cirrhosis. Eur J Gastroenterol Hepatol. 2016;28:82–89.CrossRefGoogle Scholar
  28. 28.
    Maruyama H, Okugawa H, Takahashi M, Yokosuka O. De novo portal vein thrombosis in virus-related cirrhosis: predictive factors and long-term outcomes. Am J Gastroenterol. 2013;108:568–574.CrossRefGoogle Scholar
  29. 29.
    Berry K, Taylor J, Liou IW, Ioannou GN. Portal vein thrombosis is not associated with increased mortality among patients with cirrhosis. Clin Gastroenterol Hepatol. 2015;13:585–593.CrossRefGoogle Scholar
  30. 30.
    Karvellas CJ, Cardoso FS, Wells MM, et al. Clinical impact of portal vein thrombosis prior to liver transplantation: a retrospective cohort study. Ann Hepatol. 2017;16:236–436.CrossRefGoogle Scholar
  31. 31.
    Andriulli A, Tripodi A, Angeli P, et al. Hemostatic balance in patients with liver cirrhosis: report of a consensus conference. Dig Liver Dis. 2016;48:455–467.CrossRefGoogle Scholar
  32. 32.
    Anstee QM, Goldin RD, Wright M, Martinelli A, Cox R, Thursz MR. Coagulation status modulates murine hepatic fibrogenesis: implications for the development of novel therapies. J Thromb Haemost. 2008;6:1336–1343.CrossRefGoogle Scholar
  33. 33.
    Anstee QM, Wright M, Goldin R, Thursz MR. Parenchymal extinction: coagulation and hepatic fibrogenesis. Clin Liver Dis. 2009;13:117–126.CrossRefGoogle Scholar
  34. 34.
    Northup PG, Sundaram V, Fallon MB, et al. Hypercoagulation and thrombophilia in liver disease. J Thromb Haemost. 2008;6:2–9.Google Scholar
  35. 35.
    Wanless IR, Wong F, Blendis LM, Greig P, Heathcote EJ, Levy G. Hepatic and portal vein thrombosis in cirrhosis: possible role in development of parenchymal extinction and portal hypertension. Hepatology. 1995;21:1238–1247.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Carlos Noronha Ferreira
    • 1
    Email author
  • Daniela Reis
    • 1
  • Helena Cortez-Pinto
    • 1
  • Rui Tato Marinho
    • 1
  • Afonso Gonçalves
    • 2
  • Sónia Palma
    • 2
  • Inês Leite
    • 2
  • Tiago Rodrigues
    • 2
  • Ana Júlia Pedro
    • 3
  • Paula Alexandrino
    • 1
  • Fátima Serejo
    • 1
  • Margarida Sobral Dias
    • 1
  • Paula Ferreira
    • 1
  • Mariana Vasconcelos
    • 1
  • Filipe Damião
    • 1
  • Leonor Xavier Brito
    • 1
  • Cilenia Baldaia
    • 1
  • Narcisa Fatela
    • 1
  • Fernando Ramalho
    • 1
  • José Velosa
    • 1
  1. 1.Serviço De Gastrenterologia e HepatologiaHospital de Santa Maria – Centro Hospitalar Universitário Lisboa NorteLisbonPortugal
  2. 2.Serviço De ImagiologiaHospital de Santa Maria – Centro Hospitalar Universitário Lisboa NorteLisbonPortugal
  3. 3.Serviço De Medicina IIHospital De Santa Maria - Centro Hospitalar LisboaLisbonPortugal

Personalised recommendations