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Specific mechanisms of subarachnoid hemorrhage accompanied by ischemic stroke in essential thrombocythemia: two case reports and a literature review

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JAK2 V617F mutation increases the risk of thrombosis, and both ischemic and hemorrhagic strokes can occur in essential thrombocythemia (ET). The mechanisms underlying ischemic stroke in ET are diverse, and hemorrhagic stroke has rarely been reported in ET.


Among 627 stroke patients, those identified as having ET were investigated retrospectively. A comprehensive systemic literature search of the PubMed database was also conducted.


Two cases were extracted with the diagnosis of ET who developed SAH and then ischemic stroke. In Case 1, a 47-year-old woman developed SAH in the left high convexity. Eleven hours later, acute cerebellar infarction suddenly developed due to right vertebral artery dissection. In Case 2, a 70-year-old woman developed SAH in the right high convexity. Magnetic resonance angiography showed multifocal stenotic changes in intracranial arteries. Three days later, she developed acute brain infarcts in the right middle cerebral artery territory. Eight weeks later, multifocal stenotic lesions improved. The literature review revealed 5 patients with hemorrhagic stroke and 40 patients with ischemic stroke associated with ET. Age at onset varied, female gender predominated, and the frequency of JAK2 V617F mutation was high. Atherosclerotic vascular risk factors were more common in ischemic stroke, but not in hemorrhagic stroke.


The current study describes rare cases of SAH accompanied by ischemic stroke secondary to ET along with a review of the current literature, implying specific mechanisms for cerebral artery disorders associated with JAK2 V617F mutation.

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  1. Tefferi A (2013) Polycythemia vera and essential thrombocythemia: 2013 update on diagnosis, risk-stratification, and management. Am J Hematol 88:507–516

    Article  CAS  PubMed  Google Scholar 

  2. Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, Tichelli A, Cazzola M, Skoda RC (2005) A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 352:1779–1790

    Article  CAS  PubMed  Google Scholar 

  3. Fabris F, Randi ML (2009) Essential thrombocythemia: past and present. Intern Emerg Med 4:381–388

    Article  PubMed  Google Scholar 

  4. Lussana F, Caberlon S, Pagani C, Kamphuisen PW, Buller HR, Cattaneo M (2009) Association of V617F Jak2 mutation with the risk of thrombosis among patients with essential thrombocythaemia or idiopathic myelofibrosis: a systematic review. Thromb Res 124:409–417

    Article  CAS  PubMed  Google Scholar 

  5. Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, Rodeghiero F, Randi ML, Bertozzi I, Vannucchi AM, Antonioli E, Gisslinger H, Buxhofer-Ausch V, Finazzi G, Gangat N, Tefferi A, Barbui T (2011) Risk factors for arterial and venous thrombosis in WHO-defined essential thrombocythemia: an international study of 891 patients. Blood 117:5857–5859

    Article  CAS  PubMed  Google Scholar 

  6. Richard S, Perrin J, Baillot PA, Lacour JC, Ducrocq X (2011) Ischaemic stroke and essential thrombocythemia: a series of 14 cases. Eur J Neurol 18:995–998

    Article  CAS  PubMed  Google Scholar 

  7. Kato Y, Hayashi T, Sehara Y, Deguchi I, Fukuoka T, Maruyama H, Horiuchi Y, Nagamine Y, Sano H, Tanahashi N (2015) Ischemic stroke with essential thrombocythemia: a case series. J Stroke Cerebrovasc Dis 24:890–893

    Article  PubMed  Google Scholar 

  8. Adam R, Priglinger M, Harrington T, Gottlieb D, Krause M (2014) An unusual cause of cerebellar hemorrhage in a young patient: essential thrombocythemia. J Stroke Cerebrovasc Dis 23:e373–e374

    Article  PubMed  Google Scholar 

  9. Freilinger T, Saam T, Duering M, Dichgans M, Peters N (2011) Internal carotid artery dissection and ischemic cerebral infarction in the setting of essential thrombocythemia. Clin Appl Thromb Hemost 17:E138–E140

    Article  CAS  PubMed  Google Scholar 

  10. D’Ambrosio D, Della-Morte D, Gargiulo G, Rossetti M, Rundek T, Rengo F, Abete P (2008) Intrapetrous internal carotid artery dissection and essential thrombocythemia: what relationship? A case report. Cases J 1:354

    PubMed  Google Scholar 

  11. Miller TD, Farquharson MH (2010) Essential thrombocythaemia and its neurological complications. Pract Neurol 10:195–201

    Article  PubMed  Google Scholar 

  12. Bogousslavsky J, Van Melle G, Regli F (1988) The Lausanne Stroke Registry: analysis of 1,000 consecutive patients with first stroke. Stroke 19:1083–1092

    Article  CAS  Google Scholar 

  13. Choi KD, Jo JW, Park KP, Kim JS, Lee TH, Kim HJ, Jung DS (2007) Diffusion-weighted imaging of intramural hematoma in vertebral artery dissection. J Neurol Sci 253:81–84

    Article  PubMed  Google Scholar 

  14. Kato A, Shinohara Y, Yamashita E, Fujii S, Miyoshi F, Kuya K, Ogawa T (2015) Usefulness of R2* maps generated by iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantitation sequence for cerebral artery dissection. Neuroradiology 57:909–915

    Article  PubMed  Google Scholar 

  15. Ducros A (2012) Reversible cerebral vasoconstriction syndrome. Lancet Neurol 11:906–917

    Article  PubMed  Google Scholar 

  16. Ducros A, Boukobza M, Porcher R, Sarov M, Valade D, Bousser MG (2007) The clinical and radiological spectrum of reversible cerebral vasoconstriction syndrome. A prospective series of 67 patients. Brain 130:3091–3101

    Article  PubMed  Google Scholar 

  17. Arboix A, Besses C, Acin P, Massons JB, Florensa L, Oliveres M, Sans-Sabrafen J (1995) Ischemic stroke as first manifestation of essential thrombocythemia. Report of six cases. Stroke 26:1463–1466

    CAS  PubMed  Google Scholar 

  18. Verdure P, Lefaucheur R, Guegan-Massardier E, Triquenot-Bagan A, Gerardin E, Maltete D (2012) Bilateral vertebral artery dissection and essential thrombocythemia with JAK2 mutation. Rev Neurol (Paris) 168:543–544

    Article  CAS  Google Scholar 

  19. Posfai E, Marton I, Szoke A, Borbenyi Z, Vecsei L, Csomor A, Sas K (2014) Stroke in essential thrombocythemia. J Neurol Sci 336:260–262

    Article  PubMed  Google Scholar 

  20. Trifan G, Shafi N, Testai FD (2018) Implications of Janus Kinase 2 Mutation in Embolic Stroke of Unknown Source. J Stroke Cerebrovasc Dis 27:2572–2578

    Article  PubMed  Google Scholar 

  21. Charles M, Fontoura R, Sugalski G (2016) Early recognition of intraventricular hemorrhage in the setting of thrombocytosis in the emergency department. Open Access Emerg Med 8:29–33

    Article  PubMed  PubMed Central  Google Scholar 

  22. Baek JW, Kim YD (2014) Cerebral dissecting aneurysms in patients with essential thrombocythemia. J Korean Neurosurg Soc 56:257–260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kondlapudi J, O’Connor RJ, Mawer S (2009) Cerebral haemorrhage as the presenting feature of myeloproliferative disorder. BMJ Case Rep 2009

  24. Michiels JJ, Berneman Z, Schroyens W, Finazzi G, Budde U, van Vliet HH (2006) The paradox of platelet activation and impaired function: platelet-von Willebrand factor interactions, and the etiology of thrombotic and hemorrhagic manifestations in essential thrombocythemia and polycythemia vera. Semin Thromb Hemost 32:589–604

    Article  CAS  PubMed  Google Scholar 

  25. Schievink WI (2001) Spontaneous dissection of the carotid and vertebral arteries. N Engl J Med 344:898–906

    Article  CAS  Google Scholar 

  26. Arellano-Rodrigo E, Alvarez-Larran A, Reverter JC, Villamor N, Colomer D, Cervantes F (2006) Increased platelet and leukocyte activation as contributing mechanisms for thrombosis in essential thrombocythemia and correlation with the JAK2 mutational status. Haematologica 91:169–175

    CAS  PubMed  Google Scholar 

  27. Falanga A, Marchetti M, Evangelista V, Vignoli A, Licini M, Balicco M, Manarini S, Finazzi G, Cerletti C, Barbui T (2000) Polymorphonuclear leukocyte activation and hemostasis in patients with essential thrombocythemia and polycythemia vera. Blood 96:4261–4266

    CAS  PubMed  Google Scholar 

  28. Etheridge SL, Roh ME, Cosgrove ME, Sangkhae V, Fox NE, Chen J, Lopez JA, Kaushansky K, Hitchcock IS (2014) JAK2V617F-positive endothelial cells contribute to clotting abnormalities in myeloproliferative neoplasms. Proc Natl Acad Sci U S A 111:2295–2300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Solberg LA Jr, Tefferi A, Oles KJ, Tarach JS, Petitt RM, Forstrom LA, Silverstein MN (1997) The effects of anagrelide on human megakaryocytopoiesis. Br J Haematol 99:174–180

    Article  CAS  PubMed  Google Scholar 

  30. Gisslinger H, Gotic M, Holowiecki J, Penka M, Thiele J, Kvasnicka HM, Kralovics R, Petrides PE, Group AS (2013) Anagrelide compared with hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET Study, a randomized controlled trial. Blood 121:1720–1728

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Storen EC, Tefferi A (2001) Long-term use of anagrelide in young patients with essential thrombocythemia. Blood 97:863–866

    Article  CAS  PubMed  Google Scholar 

  32. Alvarez-Larran A, Cervantes F, Pereira A, Arellano-Rodrigo E, Perez-Andreu V, Hernandez-Boluda JC, Ayats R, Salvador C, Muntanola A, Bellosillo B, Vicente V, Hernandez-Nieto L, Burgaleta C, Xicoy B, Besses C (2010) Observation versus antiplatelet therapy as primary prophylaxis for thrombosis in low-risk essential thrombocythemia. Blood 116:1205–1210 (quiz 1387)

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Yuji Ueno.

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Authors declare that they have no conflicts of interest.

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This study was conducted in accordance with the Declaration of Helsinki. The independent ethics committee at Juntendo University Hospital approved this study (19-034).

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We obtained written informed consent from all patients before enrollment in the study.

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Sugiyama, M., Ueno, Y., Kamo, H. et al. Specific mechanisms of subarachnoid hemorrhage accompanied by ischemic stroke in essential thrombocythemia: two case reports and a literature review. J Neurol 266, 1869–1878 (2019).

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