The JAK2^V617F tyrosine kinase mutation identifies clinically latent myeloproliferative disorders in patients presenting with hepatic or portal vein thrombosis

Abstract

Clinically latent myeloproliferative disorders (MPDs) are important causes of what would otherwise be considered idiopathic hepatic (HVT) or portal vein thrombosis (PVT). They may be difficult to diagnose initially because the peripheral blood count may be normal at the time of thrombosis. A strong association between an activating mutation of the gene encoding one of the Janus kinase family of tyrosine kinases (JAK2(V617F)) and the Philadelphia chromosome-negative MPDs has been identified. We have studied 19 patients with unexplained HVT or PVT and tested for JAK2(V617F). Fourteen (74%) of the 19 patients were heterozygous for JAK2(V617F) but did not meet diagnostic criteria for a MPD at the time of presentation with thrombosis. Prolonged follow-up established the presence of an overt MPD in 13 of the 14 patients after a median duration of 38 months. We recommend testing for JAK2(V617F) in all patients with unexplained HVT or PVT, to identify latent MPDs and prevent potential complications.

JAK2V617F mutation for the early diagnosis of Ph− myeloproliferative neoplasms in patients with venous thromboembolism: a meta-analysis

“…Twenty-four studies were therefore included in this systematic review. 10,21,23,25,27,30,33,37,[40][41][42][43][44][45][46][47][48][49]51,52 Interobserver agreement for study selection was excellent ( ϭ 0.96).…”

“…Studies ranged in size from 11 to 560 patients; a total of 3508 patients were included. Six case-control studies 10,23,25,27,35,40 and 18 retrospective cohort studies 21,24,30,31,34,36,37,[41][42][43][44][45][46][47][48][49]51,52 were included in our systematic review. Five studies enrolled patients consecutively.…”

“…35,42,44,46,51 A few studies differentiated between patients with homozygote and heterozygote JAK2V617F mutation, 24,34,35,41,43,44,49 and 2 studies provided data on patients with homozygote mutation JAK2V617F. [24][25][26][27][28][29][30][31][32][33][34][35] Sixteen studies, 10,21,[23][24][25]30,[35][36][37]40,43,44,46,47,49,53 including a total 831 patients, assessed the prevalence of JAK2V617F mutation in patients with SVT. Eight studies, 21,27,34,37,[40][41][42]47 …”

JAK 2V617F Mutation: Frequency and Relation to Clinical and Laboratory Features of BCR-ABL Negative Myeloproliferative Diseases

“…21 JAK2 V617F was seen in 38-43% of splancnic vein thrombosis with normal or low blood counts and in 18-37% of portal vein thrombosis. 22 In another study, JAK2 mutation was found in 74% of 19 idiopathic portal or hepatic vein thrombosis and JAK2 mutation was reported as a valuable genetic marker in latent MPD diagnosis. 23 In a study, ET patients with JAK2 V617F mutation were found to have higher Hb, neutrophile levels than patients without the mutation.…”

JAK2 (V617F) Positive Latent Myeloproliferative Neoplasm Presenting with Splanchnic Vein Thrombosis

“…It has been reported that JAK2 (V617F) mutation is present in 50-79.3 % all cases of diagnosed MPN with SVT. On the other hand, in patients with latent MPN with SVT, the incidence of JAK2 (V617F) mutation varies from 11 to 74 % [13][14][15][16][17][18][19][20][21][22][23]. Only one retrospective study reported a low prevalence rate of 9.3 % [24].…”