Abstract
Objectives
Janus kinase 2 (JAK2–V617F) mutations can cause thrombocytosis, polycythemia and hyper viscosity leading to cerebral sinus venous thrombosis (CSVT). However, data regarding the characteristics and prevalence of JAK2–V617F mutation in patients with CSVT are currently lacking. We aimed to evaluate the characteristics of CSVT patients that carry the JAK2 mutation.
Materials and methods
Data of consecutive patients with CSVT, admitted to three large academic medical centers between 2010 and 2020, were retrospectively studied. Demographics, clinical presentations, radiological and clinical outcome parameters were compared between carriers of the JAK2–V617F mutation and controls.
Results
Out of 404 patients diagnosed with CSVT, 26 patients (6.5%) were carriers of the mutation. JAK2 mutation carriers more often had thrombocytosis (54% vs. 1%, p < 0.001). Furthermore, carriers of the JAK2 mutation less often had involvement of the transverse sinus (50% vs. 68%, p = 0.021). Finally, patients with the JAK2 mutation were more prone to have intracerebral hemorrhage (ICH, 31% vs. 17%, p = 0.044), but there was no significant difference between groups in terms of mortality nor functional outcome.
Conclusions
JAK2 mutation is not uncommon in patients with CSVT and should be routinely screened for in this population. CSVT in JAK2 mutation carriers may have a tendency toward involving specific venous sinuses and is associated with a higher rate of ICH but similar overall prognosis.
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References
Bousser MG, Ferro JM (2007) Cerebral venous thrombosis: an update. Lancet Neurol 6(2):162–170
Ferro JM, Canhão P, Stam J, Bousser MG, Barinagarrementeria F (2004) Prognosis of cerebral vein and dural sinus thrombosis: results of the international study on cerebral vein and dural sinus thrombosis (ISCVT). Stroke 35(3):664–670
Shetty S, Kulkarni B, Pai N, Mukundan P, Kasatkar P, Ghosh K (2010) JAK2 mutations across a spectrum of venous thrombosis cases. Am J Clin Pathol 134(1):82–85. https://doi.org/10.1309/AJCP7VO4HAIZYATP (PMID: 20551270)
Passamonti SM, Biguzzi E, Cazzola M, Franchi F, Gianniello F, Bucciarelli P, Pietra D, Mannucci PM, Martinelli I (2012) The JAK2 V617F mutation in patients with cerebral venous thrombosis. J Thromb Haemost 10(6):998–1003. https://doi.org/10.1111/j.1538-7836.2012.04719.x (PMID: 22469236)
De Stefano V, Fiorini A, Rossi E, Za T, Farina G, Chiusolo P, Sica S, Leone G (2007) Incidence of the JAK2 V617F mutation among patients with splanchnic or cerebral venous thrombosis and without overt chronic myeloproliferative disorders. J Thromb Haemost 5(4):708–714. https://doi.org/10.1111/j.1538-7836.2007.02424.x (Epub 2007 Jan 29 PMID: 172637)
Lamy M, Palazzo P, Agius P, Chomel JC, Ciron J, Berthomet A, Cantagrel P, Prigent J, Ingrand P, Puyade M, Neau JP (2017) Should We screen for janus kinase 2 V617F mutation in cerebral venous thrombosis? Cerebrovasc Dis 44(3–4):97–104. https://doi.org/10.1159/000471891 (Epub 2017 Jun 14 PMID: 28609766)
Levraut M, Legros L, Drappier C, Béné MC, Queyrel V, Raynaud S, Martis N (2020) Low prevalence of JAK2 V617F mutation in patients with thrombosis and normal blood counts: a retrospective impact study. J Thromb Thrombolysis 50(4):995–1003. https://doi.org/10.1007/s11239-020-02100-z (PMID: 32266587)
Michiels JJ, Berneman Z, Van Bockstaele D, van der Planken M, De Raeve H, Schroyens W (2006) Clinical and laboratory features, pathobiology of platelet-mediated thrombosis and bleeding complications, and the molecular etiology of essential thrombocythemia and polycythemia vera: therapeutic implications. Semin Thromb Hemost 32:174–207. https://doi.org/10.1055/s-2006-939431 (PMID: 16673274)
Bellucci S, Michiels JJ (2006) The role of JAK2 V617F mutation, spontaneous erythropoiesis and megakaryocytopoiesis, hypersensitive platelets, activated leukocytes, and endothelial cells in the etiology of thrombotic manifestations in polycythemia vera and essential thrombocythemia. Semin Thromb Hemost 32(4 Pt 2):381–398. https://doi.org/10.1055/s-2006-942759 (PMID: 16810614)
Marchetti M, Falanga A (2008) Leukocytosis, JAK2V617F mutation, and hemostasis in myeloproliferative disorders. Pathophysiol Haemost Thromb 36(3–4):148–159. https://doi.org/10.1159/000175153 (Epub 2009 Jan 27 PMID: 19176988)
Trifan G, Shafi N, Testai FD (2018) Implications of janus kinase 2 mutation in embolic stroke of unknown source. J Stroke Cerebrovasc Dis 27(10):2572–2578. https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.05.052 (Epub 2018 Jul 26 PMID: 30056970)
Afifi K, Bellanger G, Buyck PJ, Zuurbier SM, Esperon CG, Barboza MA, Costa P, Escudero I, Renard D, Lemmens R, Hinteregger N, Fazekas F, Conde JJ, Giralt-Steinhauer E, Hiltunen S, Arauz A, Pezzini A, Montaner J, Putaala J, Weimar C, Schlamann M, Gattringer T, Tatlisumak T, Coutinho JM, Demaerel P, Thijs V (2020) Features of intracranial hemorrhage in cerebral venous thrombosis. J Neurol 267(11):3292–3298. https://doi.org/10.1007/s00415-020-10008-0 (Epub 2020 Jun 22. Erratum in: J Neurol. 2020 Aug 12. PMID: 32572620)
Pongmoragot J, Saposnik G (2012) Intracerebral hemorrhage from cerebral venous thrombosis. Curr Atheroscler Rep 14(4):382–389. https://doi.org/10.1007/s11883-012-0260-1 (PMID: 22664979)
**e J, Geng L, Yuan B, Guo Y, Zhang Z (2020) Complex intracranial vascular complications caused by essential thrombocythemia: a critical case report. BMC Neurol 20(1):407. https://doi.org/10.1186/s12883-020-01986-9
Jiao L, Huang X, Fan C et al (2021) Clinical characteristics and management of cerebral venous sinus thrombosis in patients with essential thrombocythemia. Neuropsychiatr Dis Treat 17:1195–1206. https://doi.org/10.2147/NDT.S294712 (Published 2021 Apr 22)
Duman T, Uluduz D, Midi I et al (2017) A multicenter study of 1144 patients with cerebral venous thrombosis: the VENOST study. J Stroke Cerebrovasc Dis 26(8):1848–1857. https://doi.org/10.1016/j.jstrokecerebrovasdis.2017.04.020
Saposnik G, Barinagarrementeria F, Brown RD Jr et al (2011) Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 42:1158–1192. https://doi.org/10.1161/STR.0b013e31820a8364 (PMID: 21293023)
Geyer HL, Mesa RA (2014) Therapy for myeloproliferative neoplasms: when, which agent, and how? Blood 124:3529–3537. https://doi.org/10.1182/blood-2014-05-577635 (PMID: 25472969)
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Simaan, N., Molad, J., Honig, A. et al. Characteristics of patients with cerebral sinus venous thrombosis and JAK2 V617F mutation. Acta Neurol Belg 123, 1855–1859 (2023). https://doi.org/10.1007/s13760-022-02077-x
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DOI: https://doi.org/10.1007/s13760-022-02077-x