LETTER TO THE EDITOR JAK2 V617F, hemostatic polymorphisms, and clinical features as risk factors for arterial thrombotic events in essential thrombocythemia María J. Moreno & María L. Lozano & V. Roldán & B. Bellosillo & N. García-Barberá & J. Rivera & L. Navarro-Núñez & C. Besses & V. Vicente & C. Martínez Received: 27 November 2007 / Accepted: 26 February 2008 / Published online: 26 March 2008 # Springer-Verlag 2008 Dear Editor, A recent mutation located in the JAK2 gene, JAK2 V617F, has been shown to play a transcendental role in the constitutive activation of its tyrosine kinase activity in an important number of cases of Philadelphia negative myeloproliferative disorders (Ph-MPDs). This mutation is a useful tool for diagnosing this diseases because different studies show that this mutation is highly frequent in patients with polycythemia vera (PV) and is present in around 50% of the patients with essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF) [1]. Among the clinical features and phenotypes that characterize Ph-MPD patients, thrombotic and hemorrhagic episodes have been shown to be frequent in these patients. Range values for thrombosis at diagnosis fluctuate between 34% to 39% for PV and 10% to 29% for ET [2]. For hemorrhage, the values are much more variable [3]. The mechanisms accounting for the increased risk of thrombosis and hemorrhage in Ph-MPD patients are not well understood. It has been accepted that the occurrence of previous venous thrombotic events and age increase the risk of thrombosis [4, 5]. The contribution of cardiovascular disease risk factors in the development of thrombosis in Ph-MPD patients is still unclear. Risk factors for hemor- rhage are more elusive and few have been described [2, 4]. Studies are limited concerning the impact of hereditary thrombophilia in the development of thrombotic episodes in Ph-MPD patients [6, 7]. In addition, the effect of the JAK2 F617 allele in the development of thrombotic events is still controversial [2, 8, 9]. Thus, we aimed to ascertain the role of JAK2 V617F and other genetic risk factors in the development of thrombosis in patients diagnosed with Ph-MPD. For this purpose, we evaluated the prevalence of JAK2 V617F mutation and nine additional genetic alterations [FV Leiden, PT G20210A, and ZPI R67Stop are polymorphisms associated with venous thrombosis; HPA-1 located in the αIIbβ3 integrin, HPA-2 located in von Willebrand factor receptor GIb/IX/V, GPIa C807T, and PSGL-1 are polymorphisms associated with arterial thrombosis; FVII -323 Del/Ins and TUBB1 Q43P located in the megakaryocyte-specific tubulin β1 are two polymorphisms that increase the risk of hemorrhage] in 212 patients [74 PV, 128 ET, and ten IMF] (94 males, 118 females, median age 60.5±16.1, range 21–85 years) followed during a 4-year period in Hospital Morales Meseguer (Murcia) and Hospital del Mar (Barce- lona). Thrombotic complications included venous (N =13) and major arterial thromboses (N =42) as well as microvas- cular alterations such as erythromelalgia (N =17). Several patients had two episodes of vascular events: five patients had both venous and major arterial thromboses and two patients with erythromelalgia developed an episode of arterial thrombosis. Fifteen patients had hemorrhage. We considered asymptomatic patients those with no thrombotic or hemorrhagic episodes. The analysis of the role of genetic Ann Hematol (2008) 87:763–765 DOI 10.1007/s00277-008-0474-z This study was supported, in part, by research grants SAF 2004-07535 (MEC) and 03116/PI/05 (Fundación Séneca). L. N-N. is a fellow from Ministerio de Educación y Ciencia (BES-2005-7496). C. M. is Ramón y Cajal investigator from the University of Murcia. M. J. Moreno : M. L. Lozano : V. Roldán : N. García-Barberá : J. Rivera : L. Navarro-Núñez : V. Vicente : C. Martínez (*) University of Murcia, Centro Regional de Hemodonación, C/ Ronda de Garay S/N, Murcia 30003, Spain e-mail: constant@um.es B. Bellosillo : C. Besses Hospital del Mar, IMAS, Passeig Maritim 25-29, 08003 Barcelona, Spain