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• W2045625049 abstract "Polycythemia vera (PV) and essential thrombocythemia (ET), the two most common Philadelphia-negative myeloproliferative diseases (MPD), are frequently complicated by arterial or venous thrombosis [1]. Large vessel arterial thrombosis is the predominant cause of morbidity and mortality in these patients and includes ischemic stroke, myocardial infarction, splanchnic and peripheral arterial occlusion. JAK2V617F is a recurrent mutation in MPD with an allelic frequency estimated at 95% for PV and at 50% for ET [2]. The presence of the JAK2V617F mutation has been associated with an increased risk of thrombosis in patients with MPD [3]. In particular, a high prevalence of the JAK2V617F mutation has been reported in patients with splanchnic vein thrombosis (SVT), and the detection of such a mutation in this patient population seems to be associated with an increased risk of diagnosis of occult MPD. Consequently, routine screening of the JAK2V617F mutation appears to be indicated in patients presenting with SVT [3]. In contrast, limited data are available regarding the prevalence of the JAK2V617F mutation in patients who present with arterial thrombosis without distinct features of MPD, and whether the screening for the JAK2V617F mutation in these patients is justified, in particular in the absence of major cardiovascular risk factors, remains unclear. The aim of this study was to review the literature and to assess the prevalence of the JAK2V617F mutation in patients with arterial thrombosis. We searched studies using the MEDLINE (1966 to October 2008, Week 4) and EMBASE (1980 to October 2008, Week 4) electronic databases. The search strategy was developed without any language restriction, and used the following key search words: JAK2V617F mutation, thrombosis and myeloproliferative disease. Research was supplemented by manually reviewing abstracts books from the Congress of the International Society on Thrombosis and Haemostasis (ISTH), and American Society of Haematology (ASH) (2004–2008) and the reference lists of all retrieved articles. Only studies with at least 10 patients were included. Furthermore, only adult patients (18 years or older) were considered. The following data were extracted – study characteristics (year of publication, study type) and both patient and control characteristics (i.e. number of subjects studied, median age, variation in age, gender and JAK2 genotype). Study identification, study selection and data extraction were performed independently in duplicate by two reviewers. Where there was a discrepancy between the reviewers this was resolved by discussion or by the opinion of a third reviewer, as necessary. The agreement between the reviewers was calculated using the kappa (k) statistic [4]. Weighted mean proportion of the prevalence of the JAK2V617F mutation was calculated using the random effect model. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated when studies compared the prevalence of the JAK2V617F mutation in patients with arterial thrombosis and in controls. Statistical heterogeneity was evaluated using the I2 statistic [5]. A total of 986 (295 MEDLINE, 691 EMBASE) citations and 50 abstracts from the ISTH and ASH congresses were identified by our systematic search. Of these, 220 studies were duplicated. After screening of the title and abstract using the predefined inclusion and exclusion criteria, seven studies were retrieved for more detailed evaluation [6-12]. One article was excluded because it contained duplicated data [12] and therefore six studies were included in our systematic review [6-11]. The inter-observer agreement for the study selection was total (k = 1). Baseline characteristics of the included studies are summarized in Table 1. Two studies were case controls and four were retrospective cohorts of patients. All studies were written in English. A total of 585 patients were included in our analysis: 535 patients with arterial thrombosis (345 with ischemic stroke) and 50 controls without thrombosis. Study size ranged from 14 to 178 patients. The JAK2V617F mutation was found in five patients with arterial thrombosis, with a mean prevalence of 1.1% (95% CI 0.40, 2.29%; I = 22.5%). Meta-analysis of the two case–control studies failed to demonstrate a significant increased risk of arterial thrombosis in patients with the JAK2V617F mutation as compared with controls (OR 2.18; 95% CI 0.15, 30.64; I2 32.2). The results of this systematic review suggest that the prevalence of the JAK2V617F mutation is low in patients presenting with arterial thrombosis, similar to the prevalence of this mutation reported in the general population [13]. Furthermore, the meta-analysis of the two case–control studies failed to demonstrate a significant association between the JAK2V617F mutation and arterial thrombosis in an unselected population. Taken together, these results suggest that, in general, patients with arterial thrombosis should not be screened for the presence of the JAK2V617F mutation. This is probably as a result of the fact that several other risk factors might cause arterial thrombosis, and that the JAK2V617F mutation may have only a small role, if any, in the pathogenesis of this disease. Our results should be interpreted with caution as only six studies for a total of 535 patients were included in our systematic review. However, the prevalence of the JAK2V617 mutation in these patients remained low even if we consider the upper limit of the CIs, thus strengthening the validity of our results. Furthermore, more than half of included patients had an ischemic stroke, whereas patients with myocardial infarction, intestinal ischemia and peripheral artery disease were less represented in our systematic review. However, heterogeneity among studies, calculated using the I2 statistic, was extremely low suggesting that our results could be extrapolated to all patients with arterial thrombosis. Finally, data are insufficient to draw any conclusion on the role of the JAK2V617F mutation in patients with arterial thrombosis in whom major and more frequent cardiovascular risk factors have been excluded. In conclusion, our results suggest that the JAK2V617F mutation per se is not a risk factor for arterial thrombosis and that testing for this mutation should not be included in the evaluation of these patients whereas recent studies recommended the systematic appraisal of the mutation in the diagnostic approach to splanchnic vein thrombosis. However, future studies including larger cohorts of patients will be necessary to confirm these preliminary results. The authors state they have no conflict of interest." @default.
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• W2045625049 date "2009-04-01" @default.
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• W2045625049 title "JAK2V617F mutation in patients with arterial thrombosis in the absence of overt myeloproliferative disease" @default.
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• W2045625049 doi "https://doi.org/10.1111/j.1538-7836.2009.03303.x" @default.
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