title: Relevance of the JAK2V617F mutation in patients with deep vein thrombosis of the leg.
abstract: Venous thromboembolism (VTE) can be the first presenting symptom in myeloproliferative neoplasms (MPN). Studies have demonstrated a high prevalence of the JAK2V617F mutation in patients with splanchnic vein thrombosis. Fewer studies have been done in patients with thrombosis outside the splanchnic area, showing a lower prevalence although the clinical relevance of the mutation in these patients, e.g., progression to overt MPN, remains unknown. The objective of this study was to determine the effect size of JAK2V617F in prospectively collected DNA samples of patients objectively diagnosed with deep vein thrombosis (DVT) of the leg and controls without DVT, with follow-up on JAK2V617F-positive patients to assess clinical relevance. Presence of JAK2V617F was determined in DNA samples from 187 patients with DVT and 201 controls, using quantitative RT-PCR. Hematological parameters were also analyzed. All initially JAK2V617F-positive patients were reassessed. Of 187 patients with DVT, 178 were analyzed for JAK2V617F, and in four (2.3%; 95% CI 0.1-4.4), JAK2V617F was present. Of 201 controls, 198 were analyzed; one was JAK2V617F positive (0.5%; 95% CI -0.5-1.5, OR 4.5; 95% CI 0.5-40.9). None had MPN features, nor upon reassessment after a median follow-up of 68.5 months. Four JAK2V617F-positive patients with DVT and one control without DVT did not develop overt MPN after a median follow-up of nearly 6 years. Thus, in patients with non-splanchnic venous thrombosis, JAK2V617F appears not to be clinically relevant.
authors.affiliation: Department of Hematology, Academic Medical Center, F4-224, 1100 DD Amsterdam, The Netherlands.
authors.forename: Mandy N
authors.initials: MN
authors.lastname: Lauw
authors.forename: Erik W N
authors.initials: EW
authors.lastname: Bus
authors.forename: Alexander F Y
authors.initials: AF
authors.lastname: van Wulfften Palthe
authors.forename: Michiel
authors.initials: M
authors.lastname: Coppens
authors.forename: Christa H
authors.initials: CH
authors.lastname: Homburg
authors.forename: Saskia
authors.initials: S
authors.lastname: Middeldorp
authors.forename: C Ellen
authors.initials: CE
authors.lastname: van der Schoot
authors.forename: Harry R
authors.initials: HR
authors.lastname: Koene
authors.forename: Bart J
authors.initials: BJ
authors.lastname: Biemond
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D007866:Leg / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011446:Prospective Studies; D012307:Risk Factors; D013152:Splanchnic Circulation; D054556:Venous Thromboembolism / Q000235:genetics*; D020246:Venous Thrombosis / Q000235:genetics*
chemical_list: D053614:Janus Kinase 2