Should We Screen for Janus Kinase 2 V617F Mutation in Cerebral Venous Thrombosis?

Abstract

Background: The presence of Janus Kinase 2 (JAK2) V617F mutation represents a major diagnostic criterion for detecting myeloproliferative neoplasms (MPN) and even in the absence of overt MPN, JAK2 V617F mutation is associated with splanchnic vein thrombosis. However, the actual prevalence and diagnostic value of the JAK2 V617F mutation in patients with cerebral venous thrombosis (CVT) are not known. The aims of this study were to assess the prevalence of JAK2 V617F mutation in a large group of consecutive CVT patients, to detect clinical, biological, and radiological features associated with the mutation, and to determine the long-term venous thrombosis recurrence rate in CVT patients with JAK2 mutation but without overt MPN in order to recommend the best preventive treatment. Methods: This was a prospective study conducted on consecutive patients with a first-ever radiologically confirmed CVT. JAK2 V617F mutation analysis was assessed in all the study subjects. JAK2 V617F-positive patients were followed up to detect new venous thrombotic events. Results: Of the 125 included subjects, 7 were found to have JAK2 V617F mutation (5.6%; 95% CI 2.3-11.2). Older age (p = 0.039) and higher platelet count (p = 0.004) were independently associated with JAK2 V617F positivity in patients without overt MPN. During a mean follow-up period of 59 (SD 46) months, 2 JAK2 V617F-positive patients presented with 4 new venous thromboembolic events. Conclusions: Screening for the JAK2 V617F mutation in CVT patients seems to be useful even in the absence of overt MPN and/or in the presence of other risk factors for CVT because of its relatively high prevalence and the risk of thrombosis recurrence.

Jak2 mutation expands the thrombophilic panel in children

“…It is noteworthy to mention that in adult patients not exhibiting hematologic criteria for MPN, venous thrombotic complications (especially splanchnic and cerebral thrombosis) may be the only symptom of the disease. In fact, the reported incidence of positivity to the JAK2 V617F mutation in those patients ranges from 12% to 74% in the presence of splanchnic vein thrombosis; it is estimated to be around 4% in presence of CSVT 5 . Most important, the finding of the JAK2 V617F mutation in patients with CSVT was associated with a recurrence risk of about 30%, supporting the need for a systematic screening 5 …”

“…The JAK2 V617F mutation (c.1849G>T, p.Val617Phe) is a somatic gain‐of‐function mutation 7 . Its presence is a major diagnostic criterion for Philadelphia chromosome‐negative MPN 5 . This disorder is characterized by extensive proliferation of multipotent myeloid progenitor cells, including chronic myelomonocytic leukemia, polycythemia vera, essential thrombocythemia, and primary myelofibrosis 7 .…”

“…The occurrence of hyperhomocysteinemia and dehydration, resulting from vomiting and liquid restriction with weight loss, were not considered sufficient to explain the pathogenesis of the thrombosis. Because of the recent report of the Janus Kinase 2 (JAK2) V617F mutation found in adult patients affected by CSVT in the absence of diagnostic criteria for myeloproliferative neoplasms (MPNs), we screened for this pathogenic variant as well 5‐7 . The genetic analysis of JAK2 on our 15‐year‐old patient revealed the presence of the pathogenic mutation V617F (Mut Janus Kinase2 ex14 [V617F] 31.12%, POS > 0.093).…”

Prefibrotic Myelofibrosis Presenting with Multiple Cerebral Embolic Infarcts and the Rare MPL W515S Mutation

“…High 2 Case Reports in Hematology clinical awareness is warranted to identify an underlying MPN in order that a prompt treatment is initiated (e.g., antiplatelet, cytoreductive, and phlebotomy) [24,25]. While some studies have suggested routine screening for JAK2 V617F in patients presenting with stroke and/or cerebral venous thrombosis (CVT) [26], given the lower risk of thrombosis in CALR-and MPL-mutated MPN patients and the near absence of these mutations in CVT cohorts [27,28], wider evaluation of mutation status might be reserved for those patients with sustained abnormal blood count findings. Detection of MPN-associated mutations is achieved by a number of technological approaches including Sanger sequencing, allele-specific PCR, melt curve analysis, capillary electrophoresis, pyrosequencing, digital PCR, and nextgeneration sequencing [29].…”

Pathogenetic mechanisms of thrombosis in patients with myeloproliferative neoplasm

“…[8][9][10][11][12] Testing for JAK2 mutation is also required in patients with recurrent thrombosis receiving anti-vitamin K. 13 A significant prevalence of the presence of this mutation in patients with deep vein thrombosis has not been established.…”