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Publications

Journal Article Ahead of print

PubMed: 41990577 DOI: 10.1016/j.jhepr.2026.101772

Prognostic value of factor VIII, D-dimer and high molecular risk variants assessing re-thrombosis risk in non-cirrhotic portal vein thrombosis.

JHEP Rep 8(5):101772

Authors: Anna Baiges, Bogdan Procopet, Luis Téllez, Elba Llop, Anna Darnell, Ángeles García-Criado, Fanny Turon, Oana Nicoara-Farcau, Hélène Larrue, Valeria Perez-Campuzano, Meritxell Nomdedeu, Joan Carles Reverter, Alberto Álvarez-Larrán, Dolors Colomer, Marta Garrote, Mónica López-Guerra, Sonia Torres, Sarah Shalaby, Asunción Ojeda, Lara Orts, Isabel Requejo, José Luis Calleja Panero, Christophe Bureau, Agustín Albillos, Virginia Hernández-Gea, Juan Carlos García-Pagán

Affiliations

  • Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic de Barcelona, FRCB - IDIBAPS, Universitat de Barcelona, ERN-Rare Liver (Health Care Provider of the European Reference Network on Rare Liver Disorders), CSUR (Centro de Referencia del Sistema Nacional de Salud en Enfermedad Hepática Vascular Compleja en adultos), CIBEREHD, Barcelona, Spain.
  • 3(rd) Medical Clinic, University of Medicine and Pharmacy "Iuliu Hatieganu" and Liver Unit, Regional Institute of Gastroenterology and Hepatology "Octavian Fodor", Cluj-Napoca, Romania, Cluj-Napoca, Romania.
  • Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramon y Cajal, IRCYS, Universidad de Alcalá, CIBEREHD, Madrid, Spain.
  • Gastroenterología y Hepatología, Hospital Puerta de Hierro, Majadahonda, IDIPHISA, CIBEREHD, Madrid, Spain.
  • Servei de Radiologia, Hospital Clínic de Barcelona, Barcelona, Spain.
  • Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic de Barcelona, FRCB - IDIBAPS, Universitat de Barcelona, ERN-Rare Liver (Health Care Provider of the European Reference Network on Rare Liver Disorders), CSUR (Centro de Referencia del Sistema Nacional de Salud en Enfermedad Hepática Vascular Compleja en adultos), CIBEREHD, Barcelona, Spain.
  • Hepatology department, Rangueil Hospital Toulouse, and Toulouse University, France.
  • Servei d'Hemoteràpia i Hemostàsia, Hospital Clínic de Barcelona, Barcelona, Spain.
  • Servei d'Hematologia, Hospital Clínic de Barcelona, Barcelona, Spain.
  • Secció Hematopatologia, Servei d' Anatomia Patològica, CDB, Hospital Clinic de Barcelona, IDIBAPS, Universitat de Barcelona, Spain; CIBERONC, Barcelona, Spain.
  • Secció Hematopatologia, Servei d' Anatomia Patològica, CDB, Hospital Clinic de Barcelona, IDIBAPS, Universitat de Barcelona, Spain.
  • Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic de Barcelona, FRCB - IDIBAPS, Universitat de Barcelona, ERN-Rare Liver (Health Care Provider of the European Reference Network on Rare Liver Disorders), CSUR (Centro de Referencia del Sistema Nacional de Salud en Enfermedad Hepática Vascular Compleja en adultos), CIBEREHD, Barcelona, Spain.

Abstract

BACKGROUND & AIMS

Patients with non-cirrhotic non-tumoral portal venous system thrombosis (NCNT-PVT) require long-term anticoagulation to prevent rethrombosis (either splanchnic or at any site, referred to as overall rethrombosis - oRT) when there is an underlying high-risk thrombophilic disorder or history of previous thrombotic episodes. However, up to 25% of patients without such indications still develop oRT. Elevated factor VIII (≥150%), D-dimer (≥500 ng/ml) or the presence of high molecular risk (HMR) variants have been proposed as risk predictors for oRT in these patients. This study aimed to compare the prognostic value of these three biomarkers in a cohort of patients with NCNT-PVT.

METHODS

We performed a multicenter, retrospective, observational study including 123 patients with NCNT-PVT without an indication for long-term anticoagulation.

RESULTS

During a median follow-up of 89.3 months (IQR 36-129), 33 patients (27%) developed venous oRT, with a cumulative incidence of 7%, 17% and 26% at 1, 5 and 10 years. Factor VIII ≥150% and HMR were associated with oRT risk (hazard ratio 5.92, 95% CI 2.67-13.15, p <0.01; and hazard ratio 2.07, 95% CI 1.01-4.24, p = 0.04, respectively) while D-dimer ≥500 ng/ml showed a non-significant trend. Multivariate analysis confirmed factor VIII and HMR as independent predictors.

CONCLUSIONS

Patients with unprovoked or local factor-associated PVT have a clinically relevant long-term risk of recurrence, with a 25% cumulative incidence of oRT at 10 years. Elevated factor VIII (≥150%) identifies a subgroup at particularly increased risk, and its combination with HMR variants may further refine risk stratification.

IMPACT AND IMPLICATIONS

This study addresses an important clinical gap by evaluating whether prothrombotic and genetic biomarkers can help identify patients with non-cirrhotic, non-tumoral portal vein thrombosis who remain at risk of recurrent thrombosis despite the absence of classical thrombophilia. Our results show that persistently elevated factor VIII levels, alone or combined with high molecular risk variants, are strong predictors of rethrombosis in this population. These findings may help refine recurrence-risk stratification in patients traditionally considered low risk and could support more individualized decisions regarding long-term anticoagulation and follow-up intensity.

MeSH

Factor Viii, Incidence, Portal Vein, Biomarkers, Thrombosis, Veins