Arterial thrombosis is a common complication in patients with Ph- myeloproliferative neoplasms (MPN). We searched for the risk factors of stroke in MPN patients from anagrelide registry. We analyzed the potential risk factors triggering a stroke/TIA event in 249 MPN patients with previous stroke (n = 168) or Transient Ischemic Attack (TIA) (n = 140), and in 1,193 MPN control subjects (without clinical history of thrombosis). These patients were registered in a prospective manner, providing a follow-up period after Anagrelide treatment. The median age of the patients in the experimental group was of 56 years of age (ranging from 34-76) and of 53 years of age (ranging from 26-74) in the control group (p < 0.001). Using a multivariate model, we determined the following as risk factors: JAK2V617F mutation (OR 2.106, 1.458-3.043, p = 0.006), age (OR 1.017/year, 1.005-1,029, p = 0.006), male gender (OR 1.419, 1.057-1.903, p = 0.020), MPN diagnosis (OR for PMF 0.649, 0.446-0.944, p = 0.024), BMI (OR 0.687 for BMI > 25, 0.473-0.999, p = 0.05) and high TAG levels (OR 1.734, 1.162-2.586, p = 0.008), all of which were statistically significant for CMP development. Concerning the risk factors for thrombophilia, only the antiphospholipid syndrome (OR 1.994, 1.017-3.91, p = 0.048) was noteworthy in a stroke-relevant context. There was no significant difference between the blood count of the patients prior to a stroke event and the control group, both of which were under a cytoreductive treatment. We found that age, male gender, JAK2V617F mutation, previous venous thrombosis, and hypertriglyceridemia represent independent risk factors for the occurrence of a stroke in Ph- MPN patients.

1st Medical Faculty Institute of Clinical and Experimental Hematology Charles University Prague Czech Republic

Department of Clinical Hematology Faculty Hospital Brno Masaryk University Brno Czech Republic

Faculty of Medicine Institute of Biostatistics and Analyses Masaryk University Brno Czech Republic

Institute of Hematology and Blood Transfusion Prague Czech Republic

University Hospital Hradec Králové Charles University Faculty of Medicine in Hradec Králové Hradec Králové Czech Republic

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Muxi PJ, Oliver AC (2014) Jak-2 positive myeloproliferative neoplasms. Curr Treat Options Oncol 15:147–156. https://doi.org/10.1007/s11864-014-0279-3 PubMed DOI

Barbui T, Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, Rodeghiero F, Randi ML, Bertozzi I, Gisslinger H, Buxhofer-Ausch V, De Stefano V, Betti S, Rambaldi A, Vannucchi AM, Tefferi A (2012) Development and validation of an International Prognostic Score of thrombosis in World Health Organization-essential thrombocythemia (IPSET-thrombosis). Blood 120:5128–5133. https://doi.org/10.1182/blood-2012-07-444067 PubMed DOI

Schwarz J, Ovesna P, Cerna O, Kissova J, Maaloufova Soukupova J, Brychtova Y, Doubek M, Cervinek L, Cmunt E, Dulicek P, Campr V, Kren L, Penka M (2016) Thrombosis in thrombocythemic Ph PubMed DOI

Artoni A, Bucciarelli P, Martinelli I (2014) Cerebral thrombosis and myeloproliferative neoplasms. Curr Neurol Neurosci Rep 14:496. https://doi.org/10.1007/s11910-014-0496-y PubMed DOI

Harrison CN, Bareford D, Butt N, Campbell P, Conneally E, Drummond M, Erber W, Everington T, Green AR, Hall GW, Hunt BJ, Ludlam CA, Murrin R, Nelson-Piercy C, Radia DH, Reilly JT, Van der Walt J, Wilkins B, McMullin MF (2010) Guideline for investigation and management of adults and children presenting with a thrombocytosis. Br J Haematol 149:352–375. https://doi.org/10.1111/j.1365-2141.2010.08122.x PubMed DOI

Barbui T, Barosi G, Birgegard G, Cervantes F, Finazzi G, Griesshammer M, Harrison C, Hasselbalch HC, Hehlmann R, Hoffman R, Kiladjian JJ, Kroger N, Mesa R, McMullin MF, Pardanani A, Passamonti F, Vannucchi AM, Reiter A, Silver RT, Verstovsek S, Tefferi A (2011) Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol 29:761–770. https://doi.org/10.1200/JCO.2010.31.8436 PubMed DOI PMC

Schwarz J, Pytlik R, Doubek M, Brychtova Y, Dulicek P, Campr V, Kren L, Penka M (2006) Analysis of risk factors: the rationale of the guidelines of the Czech Hematological Society for diagnosis and treatment of chronic myeloproliferative disorders with thrombocythemia. Semin Thromb Hemost 32:231–245. https://doi.org/10.1055/s-2006-939434 PubMed DOI

Cortelazzo S, Viero P, Finazzi G, D'Emilio A, Rodeghiero F, Barbui T (1990) Incidence and risk factors for thrombotic complications in a historical cohort of 100 patients with essential thrombocythemia. J Clin Oncol 8:556–562. https://doi.org/10.1200/JCO.1990.8.3.556 PubMed DOI

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. https://doi.org/10.1182/blood-2011-02-339002 PubMed DOI

Palandri F, Polverelli N, Catani L, Ottaviani E, Baccarani M, Vianelli N (2011) Impact of leukocytosis on thrombotic risk and survival in 532 patients with essential thrombocythemia: a retrospective study. Ann Hematol 90:933–938. https://doi.org/10.1007/s00277-010-1154-3 PubMed DOI

Radaelli F, Colombi M, Calori R, Zilioli VR, Bramanti S, Iurlo A, Zanella A (2007) Analysis of risk factors predicting thrombotic and/or haemorrhagic complications in 306 patients with essential thrombocythemia. Hematol Oncol 25:115–120. https://doi.org/10.1002/hon.816 PubMed DOI

Tefferi A, Thiele J, Orazi A, Kvasnicka HM, Barbui T, Hanson CA, Barosi G, Verstovsek S, Birgegard G, Mesa R, Reilly JT, Gisslinger H, Vannucchi AM, Cervantes F, Finazzi G, Hoffman R, Gilliland DG, Bloomfield CD, Vardiman JW (2007) Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood 110:1092–1097. https://doi.org/10.1182/blood-2007-04-083501 PubMed DOI

Schwarz J, Penka M, Campr V, Pospisilova D, Kren L, Novakova L, Bodzasova C, Brychtova Y, Cerna O, Dulicek P, Joniasova A, Kissova J, Koristek Z, Schutzova M, Vonke I, Walterova L (2011) Diagnosis and treatment of BCR/ABL-negative myeloproliferative diseases–principles and rationale of CZEMP recommendations. Vnitr Lek 57:189–213 PubMed

Murphy S, Peterson P, Iland H, Laszlo J (1997) Experience of the Polycythemia Vera Study Group with essential thrombocythemia: a final report on diagnostic criteria, survival, and leukemic transition by treatment. Semin Hematol 34:29–39 PubMed

Lee HS, Park LC, Lee EM, Lee SJ, Shin SH, Im H, Do KM, Kim EJ, Ye BJ, Song MK, Kim SH, Lee SM, Lee WS, Kim YS (2012) Incidence rates and risk factors for vascular events in patients with essential thrombocythemia: a multicenter study from Korea. Clin Lymphoma Myeloma Leukemia 12:70–75. https://doi.org/10.1016/j.clml.2011.10.002 DOI

Schneider AT, Pancioli AM, Khoury JC, Rademacher E, Tuchfarber A, Miller R, Woo D, Kissela B, Broderick JP (2003) Trends in community knowledge of the warning signs and risk factors for stroke. JAMA J Am Med Assoc 289:343–346 DOI

Nobel L, Mayo NE, Hanley J, Nadeau L, Daskalopoulou SS (2014) MyRisk_Stroke calculator: a personalized stroke risk assessment tool for the general population. J Clin Neurol 10:1–9. https://doi.org/10.3988/jcn.2014.10.1.1 PubMed DOI PMC

Wolf PA, D'Agostino RB, Belanger AJ, Kannel WB (1991) Probability of stroke: a risk profile from the Framingham Study. Stroke 22:312–318 DOI

Pastuszak Z, Kozniewska E, Stepien A, Piusinska-Macoch A, Czernicki Z, Koszewski W (2018) Importance rating of risk factors of ischemic stroke in patients over 85 years old in the polish population. Neurol Neurochir Pol 52:88–93. https://doi.org/10.1016/j.pjnns.2017.11.007 PubMed DOI

Kjeldsen SE (2017) Hypertension and cardiovascular risk: general aspects. Pharmacol Res. https://doi.org/10.1016/j.phrs.2017.11.003 PubMed DOI

Sanchez-Inigo L, Navarro-Gonzalez D, Fernandez-Montero A, Pastrana-Delgado J, Martinez JA (2017) Risk of incident ischemic stroke according to the metabolic health and obesity states in the Vascular-Metabolic CUN cohort. Int J Stroke 12:187–191. https://doi.org/10.1177/1747493016672083 PubMed DOI

de Lau LM, Leebeek FW, de Maat MP, Koudstaal PJ, Dippel DW (2010) Screening for coagulation disorders in patients with ischemic stroke. Expert Rev Neurotherapeutics 10:1321–1329. https://doi.org/10.1586/ern.10.104 DOI

Kenet G, Lutkhoff LK, Albisetti M, Bernard T, Bonduel M, Brandao L, Chabrier S, Chan A, deVeber G, Fiedler B, Fullerton HJ, Goldenberg NA, Grabowski E, Gunther G, Heller C, Holzhauer S, Iorio A, Journeycake J, Junker R, Kirkham FJ, Kurnik K, Lynch JK, Male C, Manco-Johnson M, Mesters R, Monagle P, van Ommen CH, Raffini L, Rostasy K, Simioni P, Strater RD, Young G, Nowak-Gottl U (2010) Impact of thrombophilia on risk of arterial ischemic stroke or cerebral sinovenous thrombosis in neonates and children: a systematic review and meta-analysis of observational studies. Circulation 121:1838–1847. https://doi.org/10.1161/CIRCULATIONAHA.109.913673 PubMed DOI

Montanaro VV, Freitas DD, Ruiz MC, Cavalcanti EB, Marinho PB, Freitas MC, Oliveira EM (2017) Ischemic stroke in young adults: profile of SARAH Hospital Brasilia from 2008 to 2012. Neurologist 22:61–63. https://doi.org/10.1097/NRL.0000000000000110 PubMed DOI

Dulicek P, Ivanova E, Kostal M, Sadilek P, Beranek M, Zak P, Hirmerova J (2017) Analysis of risk factors of stroke and venous thromboembolism in females with oral contraceptives use. Clin Appl Thromb. https://doi.org/10.1177/1076029617727857 DOI

Cervera R (2017) Antiphospholipid syndrome. Thromb Res 151(1):S43–S47. https://doi.org/10.1016/S0049-3848(17)30066-X PubMed DOI

Okuma H, Kitagawa Y (2013) Diagnosis and potential treatment of antiphospholipid syndrome-related mainly on ischemic stroke. Brain Nerve 65:1319–1332 PubMed

Rahemtullah A, Van Cott EM (2007) Hypercoagulation testing in ischemic stroke. Arch Pathol Lab Med 131:890–901. https://doi.org/10.1043/1543-2165(2007)131[890:HTIIS]2.0.CO;2 PubMed DOI

Buxhofer-Ausch V, Steurer M, Sormann S, Schloegl E, Schimetta W, Gisslinger B, Ruckser R, Gastl G, Gisslinger H (2016) Influence of platelet and white blood cell counts on major thrombosis-analysis from a patient registry in essential thrombocythemia. Eur J Haematol 97:511–516. https://doi.org/10.1111/ejh.12759 PubMed DOI

Carobbio A, Finazzi G, Antonioli E, Guglielmelli P, Vannucchi AM, Delaini F, Guerini V, Ruggeri M, Rodeghiero F, Rambaldi A, Barbui T (2008) Thrombocytosis and leukocytosis interaction in vascular complications of essential thrombocythemia. Blood 112:3135–3137. https://doi.org/10.1182/blood-2008-04-153783 PubMed DOI PMC

van Genderen PJ, Leenknegt H, Michiels JJ, Budde U (1996) Acquired von Willebrand disease in myeloproliferative disorders. Leuk Lymphoma 22(1):79–82. https://doi.org/10.3109/10428199609074364 PubMed DOI