JAK2V617F Mutation Screening as Part of the Hypercoagulable Workup in the Absence of Splanchnic Vein Thrombosis: Assessment of Value in a Series of 664 Consecutive Patients.
Authors: Pardanani Animesh , Lasho Terra L. , Hussein Kebede , Schwager Susan , Finke Christy , Pruthi Rajiv K. , Tefferi Ayalew 
Published: October 2019

Abstract
Background: JAK2V617F is a recurring mutation in patients with polycythemia vera (PV) (95%) and essential thrombocythemia (ET) (50%), diseases that are frequently complicated by arterial and/or venous thrombosis. JAK2V617F is also frequently identified in patients with splanchnic vein thrombosis, including in those with occult myeloproliferative disorder (MPD). We previously reported a low prevalence of JAK2V617F in thrombosis patients - only 2% of 210 patients with non-splanchnic vein thrombosis (Leukemia, 2007 Aug;21(8):1828–9), and <1% of 136 patients with arterial stroke (J Thromb Haemost. 2007 Aug;5(8):1784–5). Here, we expanded the analysis to 664 thrombosis patients to describe:
JAK2V617F prevalence, and clinical course of patients harboring this mutation.
Methods: In Phase I, we screened 439 consecutive patients who underwent thrombophilia testing at our institution in early 2005 - patients with splanchnic vein thrombosis or overt MPD were excluded. In Phase II, we identified 228 additional patients considered to be at high risk for harboring JAK2V617F, who were seen at our institution from 2004 to 2006. JAK2V617F screening (assay sensitivity <1%) was performed as described in the aforementioned references.
Results: In the initial cohort of 439 patients (median age=56 years; range 17–93 years; 222 female), 136 (31%) presented with stroke, 114 (26%) with deep venous thrombosis (DVT), 95 (22%) with pulmonary embolism (PE), 50 (11%) with DVT and PE, 10 (2%) with central retinal vein occlusion (CRVO), 7 (2%) with cerebral vein thrombosis, and the remaining 27 (6%) with other thromboses. Five patients (MC1-MC5; median age=78 years) were found to harbor JAK2V617F (prevalence=1%) - none had overt clinical features of MPD and all harbored a low level of JAK2V617F in peripheral blood (median=5–2%; range=2.2–7.5%) (Table). One patient (MC2) carried the Prothrombin G20210A mutation In the subsequent cohort, we studied 197 patients (median age=39 years; range=16–84 years) with recurrent DVT and/or PE, and 28 patients (median age=27 years; range=31–49 years) with acute myocardial infarction at a young age (<50 years). One patient (MC6) who presented with recurrent idiopathic DVT was found to harbor JAK2V617F (prevalence <0.5%) (Table) - this patient had no features of underlying MPD and the mutation burden was low (9%). After a median follow up of 27 months (range=4–66 months), none of the 6 patients harboring JAK2V617F has developed overt MPD.
Conclusions: In patients with thrombosis, JAK2V617F is infrequently detected in the absence of overt MPD and/or involvement of splanchnic veins. Thus, JAK2V617F screening cannot be recommended as part of the hypercoagulable workup in routine clinical practice in this setting. The risk of developing overt MPD may be quite low for patients harboring a low JAK2V617F burden at the time of thrombosis although longer follow up is needed in this regard.
Furthermore, the thrombosis risk may be well controlled with standard warfarin therapy, and the role of myelosuppressive agents (eg. hydroxyurea) is unclear in these patients.
Characteristics of patients harboring JAK2V617F Patient Age Sex Thrombosis JAK2V617F allele burden MPD Follow up (months) Status MC1 84 M PE, DVT 5.3% No 66 Alive MC2 82 F PE, cerebral vein 5% No 38 Alive MC3 74 F PE 2.2% No 4 Dead MC4 78 F Central retinal vein 5.2% No 22 Alive MC5 63 M Stroke 7.5% No 30 Alive MC6 69 M Recurrent DVT No No 24 Alive