title: Role of the JAK2 mutation in the diagnosis of chronic myeloproliferative disorders in splanchnic vein thrombosis.
abstract: The diagnosis of an underlying chronic myeloproliferative disorder (CMPD) is often problematic in patients with primary extrahepatic portal vein obstruction (EHPVO) or Budd-Chiari syndrome (BCS); indeed, conventional clinical and hematological parameters usually yield insufficient information. To assess the diagnostic contribution of the gain-of-function mutation V617F of the JAK2 gene, 93 patients with EHPVO or BCS were investigated. JAK2 V617F was identified in 35.6% of 73 patients with EHPVO and in 40% of 20 patients with BCS. Taking the JAK2 mutation as a test with the highest positive predictive value for the diagnosis of CMPD, conventional clinical-hematological parameters had a sensitivity for CMPD lower than 48%. Bone marrow (BM) histology provided a diagnosis of CMPD in 41/74 (55.4%) patients, with a sensitivity of 93.5%. Clonality of hematopoiesis as assessed by granulocyte X-chromosome inactivation was present in 65.1% of 43 informative female patients, with a sensitivity of 86.6%. By resolving the sensitivity bias of the JAK2 mutation with the results of BM histology and clonality assay, CMPD was diagnosed in 53% of patients with EHPVO or BCS. In conclusion, CMPD is the major cause of primary EHPVO or BCS. JAK2 V617F is a very reliable and noninvasive molecular marker for CMPD and should be used as a first test for diagnosis.
authors.affiliation: Gastroenterology Unit and Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Medicine and Medical Specialties, University of Milan and IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Primignani
authors.forename: Giovanni
authors.initials: G
authors.lastname: Barosi
authors.forename: Gaetano
authors.initials: G
authors.lastname: Bergamaschi
authors.forename: Umberto
authors.initials: U
authors.lastname: Gianelli
authors.forename: Federica
authors.initials: F
authors.lastname: Fabris
authors.forename: Raffaella
authors.initials: R
authors.lastname: Reati
authors.forename: Alessandra
authors.initials: A
authors.lastname: Dell'Era
authors.forename: Paolo
authors.initials: P
authors.lastname: Bucciarelli
authors.forename: Pier Mannuccio
authors.initials: PM
authors.lastname: Mannucci
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology; D006502:Budd-Chiari Syndrome / Q000175:diagnosis*; D002648:Child; D003251:Constriction, Pathologic; D005260:Female; D006801:Humans; D006975:Hypertension, Portal / Q000175:diagnosis*; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000175:diagnosis* / Q000235:genetics; D011169:Portal Vein / Q000473:pathology; D012189:Retrospective Studies; D013152:Splanchnic Circulation; D020246:Venous Thrombosis / Q000175:diagnosis* / Q000235:genetics
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2