Next generation sequencing in the diagnosis of non-cirrhotic splanchnic vein thrombosis.

Jul 20, 2020

Contributor: Marta Magaz,Alberto Alvarez-Larrán,Dolors Colomer,Mónica López-Guerra,M Ángeles García-Criado,Gabriel Mezzano,Ernest Belmonte,Pol Olivas,Guillem Soy,Francisco Cervantes,Anna Darnell,José Ferrusquía-Acosta,Anna Baiges,Fanny Turon,Virginia Hernández-Gea,Juan Carlos García-Pagán

Next generation sequencing in the diagnosis of non-cirrhotic splanchnic vein thrombosis.

Myeloproliferative neoplasms (MPN) are the most frequent cause of non-tumoral non-cirrhotic splanchnic vein thrombosis (NC-SVT). Diagnosis of MPN is based on blood cell count alterations, bone marrow histology and detection of specific gene mutations. Next generation sequencing (NGS) allows the simultaneous evaluation of multiple genes implicated in myeloid clonal pathology. The aim of this study was to evaluate the potential role of NGS in the etiology of NC-SVT.
DNA samples from 80 patients, (75 with idiopathic or exclusively local factor (Idiop/loc-NC-SVT) and 5 with MPN and NC-SVT (SVT-MPN) negative for JAK2 (V617F and exon 12), CALR and MPL mutations by classic techniques) were analyzed by NGS. Mutations involved in myeloid disorders different from JAK2, CALR and MPL genes were categorized as High Molecular Risk (HMR)-variants or Variants of Unknown Significance (VUS).
In 2/5 triple-negative SVT-MPN cases (40%) a mutation in exon 12 of JAK2 was identified. JAK2-exon 12 mutation was also identified in 1/75 patients with idiop/loc-NC-SVT. Moreover, 28/74 (37.8%) of the remaining idiop/loc-NC-SVT had at least one HMR variant. Sixty-two patients with idiop/loc-NC-SVT were not receiving long-term anticoagulation and five of them (8.1%) had recurrent NC-SVT. This cumulative incidence was significantly higher in patients with HMR-variants than in those without.
NGS identified JAK2-exon12 mutations not previously detected by conventional techniques. In addition, NGS detected HMR-variants in approximately one third of patients with idiop/loc-NC-SVT. These patients seem to have a higher risk of splanchnic rethrombosis. NGS might be a useful diagnostic tool in NC-SVT.

Copyright © 2020. Published by Elsevier B.V.

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About The Expert

Marta Magaz

Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona. CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas). Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver).

Alberto Alvarez-Larrán

Hematology Department, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Spain.

Dolors Colomer

Hematopathology Section, Pathology Department, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERONC (Centro de Investigación Biomédica en Red en Cancer), University of Barcelona. Barcelona, Spain.

Mónica López-Guerra

Hematopathology Section, Pathology Department, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERONC (Centro de Investigación Biomédica en Red en Cancer), University of Barcelona. Barcelona, Spain.

M Ángeles García-Criado

Abdominal Radiology Section, Radiology Department, Hospital Clínic, University of Barcelona, Barcelona.

Gabriel Mezzano

Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona. CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas). Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver).

Ernest Belmonte

Abdominal Radiology Section, Radiology Department, Hospital Clínic, University of Barcelona, Barcelona.

Pol Olivas

Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona. CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas). Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver).

Guillem Soy

Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona. CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas). Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver).

Francisco Cervantes

Hematology Department, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Spain.

Anna Darnell

Abdominal Radiology Section, Radiology Department, Hospital Clínic, University of Barcelona, Barcelona.

José Ferrusquía-Acosta

Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona. CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas). Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver).

Anna Baiges

Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona. CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas). Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver).

Fanny Turon

Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona. CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas). Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver).

Virginia Hernández-Gea

Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona. CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas). Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver).

Juan Carlos García-Pagán

Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona. CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas). Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver). Electronic address: jcgarcia@clinic.cat.

References

PubMed