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ADAMTS-13/von Willebrand factor ratio: A prognostic biomarker for portal vein thrombosis in compensated cirrhosis. A prospective observational study

  • Author Footnotes
    1 These Authors contributed equally to this study
    Monica Sacco
    Footnotes
    1 These Authors contributed equally to this study
    Affiliations
    Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica S. Cuore, Facoltà di Medicina e Chirurgia “Agostino Gemelli”, Roma, Italy
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  • Author Footnotes
    1 These Authors contributed equally to this study
    Maira Tardugno
    Footnotes
    1 These Authors contributed equally to this study
    Affiliations
    Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica S. Cuore, Facoltà di Medicina e Chirurgia “Agostino Gemelli”, Roma, Italy
    Search for articles by this author
  • Stefano Lancellotti
    Affiliations
    Servizio Malattie Emorragiche e Trombotiche, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Roma, Italy
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  • Antonietta Ferretti
    Affiliations
    Servizio Malattie Emorragiche e Trombotiche, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Roma, Italy
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  • Francesca Romana Ponziani
    Affiliations
    Dipartimento di Scienze Mediche e Chirurgiche, Hepatology Service, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica S. Cuore, Roma, Italy
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  • Laura Riccardi
    Affiliations
    Dipartimento di Scienze Mediche e Chirurgiche, Hepatology Service, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica S. Cuore, Roma, Italy
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  • Maria Assunta Zocco
    Affiliations
    Dipartimento di Scienze Mediche e Chirurgiche, Hepatology Service, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica S. Cuore, Roma, Italy
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  • Author Footnotes
    3 Current affiliation: Dipartimento di Medicina d'Urgenza ed Emergenza, Università “La Sapienza”, Facoltà di Medicina e Psicologia, and Ospedale S. Andrea, Roma, Italy
    Antonio De Magistris
    Footnotes
    3 Current affiliation: Dipartimento di Medicina d'Urgenza ed Emergenza, Università “La Sapienza”, Facoltà di Medicina e Psicologia, and Ospedale S. Andrea, Roma, Italy
    Affiliations
    Dipartimento di Scienze Mediche e Chirurgiche, Hepatology Service, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica S. Cuore, Roma, Italy
    Search for articles by this author
  • Francesco Santopaolo
    Affiliations
    Dipartimento di Scienze Mediche e Chirurgiche, Hepatology Service, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica S. Cuore, Roma, Italy
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  • Author Footnotes
    2 Raimondo De Cristofaro and Maurizio Pompili are shared senior authorship
    Maurizio Pompili
    Footnotes
    2 Raimondo De Cristofaro and Maurizio Pompili are shared senior authorship
    Affiliations
    Dipartimento di Scienze Mediche e Chirurgiche, Hepatology Service, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica S. Cuore, Roma, Italy
    Search for articles by this author
  • Author Footnotes
    2 Raimondo De Cristofaro and Maurizio Pompili are shared senior authorship
    Raimondo De Cristofaro
    Correspondence
    Corresponding author at: Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica S. Cuore – Facoltà di Medicina e Chirurgia “Agostino Gemelli” – Roma Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Roma Largo A. Gemelli, 8, 00168, Roma, Italy.
    Footnotes
    2 Raimondo De Cristofaro and Maurizio Pompili are shared senior authorship
    Affiliations
    Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica S. Cuore, Facoltà di Medicina e Chirurgia “Agostino Gemelli”, Roma, Italy

    Servizio Malattie Emorragiche e Trombotiche, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Roma, Italy
    Search for articles by this author
  • Author Footnotes
    1 These Authors contributed equally to this study
    2 Raimondo De Cristofaro and Maurizio Pompili are shared senior authorship
    3 Current affiliation: Dipartimento di Medicina d'Urgenza ed Emergenza, Università “La Sapienza”, Facoltà di Medicina e Psicologia, and Ospedale S. Andrea, Roma, Italy

      Abstract

      Background and aims

      In cirrhosis, decreased portal flow velocity, thrombophilia factors, and portal hypertension are considered risk factors for portal vein thrombosis (PVT). In cirrhosis, the transformation of the stellate cells causes a progressive decrease of ADAMTS-13, while VWF multimers secretion by endothelial cells is strongly enhanced. This imbalance leads to an accumulation of ultra-large VWF multimers that in sinusoidal circulation could favor PVT both in intra- and extra-hepatic branches, mostly in decompensated cirrhosis. This prospective study was aimed at identifying possible clinical, biochemical, and hemostatic factors predictive for non-tumoral PVT in a cohort of patients with compensated cirrhosis.

      Methods

      Seventynine compensated cirrhosis patients were prospectively followed for 48 months, receiving a periodic Doppler-ultrasound liver examination associated with an extensive evaluation of clinical, biochemical, and hemostatic profile.

      Results

      Five patients developed PVT (cumulative prevalence = 6.3%), occurring 4–36 months after enrollment. In logistic regression analysis, the ADAMTS-13/VWF:GpIbR ratio < 0.4 was the only independent variable significantly associated with PVT (OR 14.6, 95% C.I.:1.36–157.2, p = 0.027). A Cox-regression-analysis confirmed this finding (HR = 7.7, p = 0.027).

      Conclusions

      The ADAMTS-13/VWF ratio < 0.4 measured in compensated cirrhosis could be a reliable predictive biomarker for PVT development, paving the way to novel therapeutic strategies to prevent and treat PVT in this clinical setting.

      Keywords

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