Role of calreticulin mutations in the aetiological diagnosis of splanchnic vein thrombosis

J Hepatol. 2015 Jan;62(1):72-4. doi: 10.1016/j.jhep.2014.08.032. Epub 2014 Aug 27.

Abstract

Background & aims: Myeloproliferative neoplasms are the most common aetiological cause of splanchnic vein thrombosis (SVT). In these patients, the JAK2V617F mutation has facilitated the diagnosis of an underlying myeloproliferative neoplasm (MPN). Recently, somatic mutations of the calreticulin (CALR) gene have been identified in MPN patients lacking the JAK2 mutation. The aim of the present study was to ascertain whether CALR mutations could also play a role in the diagnosis of masked MPN in SVT.

Methods: We included 209 patients with SVT (140 with PVT and 69 with Budd-Chiari syndrome) who had a complete aetiological diagnostic work-out. They were investigated for CALR mutations.

Results: CALR mutations were found in 4 of the 209 patients (1.9%). They represented 5.4% of patients with an underlying MPN of whom all had already been diagnosed with a MPN using conventional criteria including bone marrow biopsy findings.

Conclusions: In the screening of underlying MPNs in patients with SVT, given its high frequency in these disorders, the JAK2 mutation must be evaluated first and, if negative, CALR mutations should also be investigated. This approach would increase the diagnostic yield of masked MPNs by reducing the need for additional studies.

Keywords: Calreticulin mutations; JAK2 mutations; Myeloproliferative neoplasms; Splanchnic vein thrombosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Calreticulin / genetics*
  • Calreticulin / metabolism
  • DNA / genetics*
  • DNA Mutational Analysis
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Mesenteric Vascular Occlusion / diagnosis
  • Mesenteric Vascular Occlusion / genetics*
  • Mesenteric Vascular Occlusion / metabolism
  • Mesenteric Veins
  • Middle Aged
  • Mutation*
  • Polymerase Chain Reaction
  • Retrospective Studies
  • Ultrasonography, Doppler, Color
  • Venous Thrombosis / diagnosis
  • Venous Thrombosis / genetics*
  • Venous Thrombosis / metabolism

Substances

  • CALR protein, human
  • Calreticulin
  • DNA