Regular Article Outcome of patients with splanchnic venous thrombosis presenting without overt MPN: A role for the JAK2 V617F mutation re-evaluation Donatella Colaizzo a , Lucio Amitrano b , Maria Anna Guardascione b , Giovanni Luca Tiscia a , Giovanna D'Andrea c , Vittoria A.C. Longo c , Elvira Grandone a , Maurizio Margaglione c, ⁎ a Unita' di Aterosclerosi e Trombosi, I.R.C.C.S. "Casa Sollievo della Sofferenza", S. Giovanni Rotondo, Italy b Divisione di Gastroenterologia, Ospedale “A. Cardarelli”, Napoli, Italy c Genetica Medica, Università di Foggia, Italy abstract article info Article history: Received 10 June 2013 Received in revised form 11 July 2013 Accepted 12 July 2013 Available online 1 August 2013 Keywords: Mutation Myeloproliferative disease Risk factors Splanchnic circulation Venous thrombosis Introduction: Although investigation for JAK2 V617F mutation is recommended in patients presenting with splanchnic venous thrombosis (SVT), no specific clinical advice is given to SVT patients presenting without myeloproliferative neoplasms (MPN) and JAK2 V617F mutation. In MPN-free SVT patients, to investigate the clinical outcome, the clinical impact of re-evaluation for the JAK2 V617F mutation, and relationships with the occurrence and time to diagnosis of MPN. Materials and Methods: A cohort of non-cirrhotic SVT patients, enrolled at a single centre and prospec- tively analyzed. Results: In 121 SVT patients prospectively followed from 1994 to 2012, a MPN was present in 28 (23.1%). Additional 13 patients (10.7%) showed only the JAK2 V617F mutation. During the follow-up, the JAK2 V617F mutation and/or MPN were identified in 8 patients (median time of development: 21 months, range 6-120), whereas 72 remained (MPN and JAK2 V617F)-free until the end of the observation. The mortality rate was higher among patients presenting with MPN and/or the JAK2 V617F mutation than in patients who developed later or remained disease-free (p = 0.032). The thrombosis-free survival was lower in patients with (p = 0.04) or developing later MPN and the JAK2 V617F mutation (p = 0.005) than in patients (MPN and JAK2 V617F)-free. The incidence of bleeding was similar among groups. Conclusions: MPN with or without circulating positive clones for JAK2 V617F mutation can occur long after a SVT, identifying at risk patients for new thrombotic events. If confirmed in other studies, re-evaluation for JAK2 V617F mutation may be of help in early MPN detection and clinical management of SVT patients. © 2013 Elsevier Ltd. All rights reserved. Introduction Myeloproliferative neoplasms (MPN) represent a main factor for thrombosis in the portal, mesenteric, or hepatic area [1–4]. On the other hand, splanchnic venous thrombosis (SVT) significantly affects morbidity and mortality of patients with MPN and are associated with severe organ damage and a high mortality [5], being the main predictor of death in both Polycytemia Vera (PV) and Essential Thrombocythemia (ET). In some cases these complications are the first presentations of the disease [6]. The JAK2 V617F mutation, an event occurring in 95% of patients with PV and in about half of the patients with ET or Myelofibrosis (MF) [7,8], has been found in most patients with non-cirrhotic SVT [9,10], a heterogeneous group of disorders [11], and a few of them do not suffer from MPN. Available results indicate that the prevalence of the JAK2 V617F mu- tation is high in SVT patients but not in patients with venous thrombosis at other sites, fostering the search for MPN in patients with these clinical phenotypes [9,12]. Actually, the mutation causes a JAK2 constitutive ac- tivation [13], and the specific association between this mutation and the unusual site of thrombosis could also be explained by the effects in the splanchnic system, possibly affecting leukocyte activation and endothe- lium functions [14,15]. On the other hand, it has been suggested that screening for the V617F JAK2 mutation is relevant in patients with SVT, a positive finding being a strong predictor of a subsequent diagno- sis of a MPN, but not of a specific subtype [9,10,12,16,17]. Thus, current management recommendations emphasise the importance of prognos- tic stratification, especially with regard to the thrombotic risk, in deter- mining the start and nature of therapy [18]. Although investigation for these risk factors is recommended, also because concurrence of ac- quired and inherited prothrombotic disorders is common, no specific clinical advice is given to SVT patients without MPN or JAK2 V617F mu- tation. Although available information suggests the occurrence of MPN after SVT [19], very few information does exist on the clinical course Thrombosis Research 132 (2013) e99–e104 ⁎ Corresponding author at: Medical Genetics, Dipt. of Clinical and Experimental Medicine, University of Foggia, viale Pinto, Foggia 71100 – Italy. Tel/fax.: +39 0881 736082. E-mail address: m.margaglione@unifg.it (M. Margaglione). 0049-3848/$ – see front matter © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.thromres.2013.07.014 Contents lists available at ScienceDirect Thrombosis Research journal homepage: www.elsevier.com/locate/thromres