Is the JAK2 V617F Mutation a Hallmark for Different Forms of Thrombosis?

Abstract

Background/Aims: The association between venous thrombosis outside the splanchnic area as well arterial thromboembolism and the JAK2 V617F mutation, an important marker for chronic myeloproliferative neoplasms (MPN), is not completely clear. Methods: Four hundred forty-four patients with venous thrombosis of the lower/upper limbs and/or pulmonary embolism and 60 patients with ischemic stroke were screened for the JAK2 V617F mutation, factor V Leiden, and factor II G20210A. Results: The JAK2 V617F mutation was detected in 1.4% of patients with venous thrombosis and in 3.3% of patients with ischemic stroke. Because 6 out of 2,430 control individuals with no medical history of venous thrombosis, stroke, or MPN were positive for the JAK2 V617F mutation, a significant association was observed (OR 5.53, CI 1.77–17.2, p = 0.0053 for venous thrombosis; OR 13.9, CI 2.75–70.5, p = 0.0145 for stroke). Conclusion: We provide evidence of the association between the JAK2 V617F mutation and different forms of thrombosis. This association is comparable with the association between inherited risk factors (factor V Leiden and factor II G20210A) and thrombotic events, but with a much lower prevalence of the mutation. Finally, the JAK2 V617F mutation is not absent from the general population despite being considered somatic and an acquired genetic variation.

JAK2V617Fmutation is highly prevalent in patients with ischemic stroke: a case-control study

“…Several other studies have assessed the prevalence of the JAK2V617F mutation in patients with ischemic stroke 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ( Table 5 ), yet they differ from our study in 3 important ways. First, most previous studies only included patients with ischemic stroke who were referred for thrombophilia testing.…”

JAK2V617FMutation Is Not Associated with Thrombosis in Behcet Syndrome

“…Interestingly, Zerjavic et al asserted having found a significant association between ischemic stroke and JAK2 V617F mutation in patients without MPNs. 47 Arterial thrombosis including CVEs was diagnosed in 20 (11%) of our patients with MPN. Recently, 3 large meta-analyses showed evidence for increased risk of arterial thrombosis in patients with JAK2 V617F -positive ET (OR, 1.68-2.09).…”

Recurrent ischaemic cerebrovascular events as presenting manifestations of myeloproliferative neoplasms

“…Furthermore, one patient presented with a fulminant cerebral venous sinus thrombosis, resulting in cerebral ischaemia with hemorrhagic transformation. This case indicates – besides the enhanced arterial thrombotic risk – the predisposition for venous thrombosis (including Budd–Chiari syndrome, portal/mesenteric venous thrombosis and pulmonary embolism) that MPN patients harbor .…”

“…Additionally, assessment of inflammation markers, iron stores, mean corpuscular volume, lactate dehydrogenase and differential blood tests should follow. Although JAK2 gene mutation screening should not be routinely performed in stroke patients when a manifest or latent MPN is not suspected , upon MPN suspicion, screening for JAK2 V617F mutation is mandatory . If JAK2 V617F mutation screening remains negative, screening for further specific molecular markers (e.g.…”