10 Questions To Ask Concerning NVP-BGJ398

2012a; Passamonti et al. 2012]. Other risk score models include this variable, however. The reasonable conclusion may be that there probably is a weak correlation, however not dominating. CV risk factors have been included in multivariate analysis and have been found to correlate with a GNAT2 higher incidence of thrombosis in several studies [Barbui et al. 2012a; Passamonti et al. 2012]. They are therefore included in some risk score models, but not all. Several risk score models have been published recently that all seem to differ reasonably well between patient groups with high, medium and low risk. However, they do not use the same variables, but different sets of criteria hold up in multivariate analysis in different studies [Passamonti et al. 2012; Tefferi and Barbui, 2013; Fu et al. 2014; Montanaro et al. 2014]. Results are sometimes quite confusing. In a large recent study, 8 studies with >300 patients each (range 311�C1220) were compared with regard to the result of multivariate analysis. Variables like WBC >11?��?109/l and JAK2 positivity/allele burden were very inconsistent as predictors, whereas age, previous thrombosis and CV risk factors were more consistent [Montanaro et al. 2014]. Hemostasis and cell interaction Relatively few groups have previously worked in this area compared with other risk factors for thrombosis, but it has been known for a long time that MPN patients have important dysfunctions in the hemostatic system. Platelets as well as leukocytes are activated, and their interaction disturbed [Falanga et al. 2005]. Furthermore, recent studies have shown high levels of membrane bound as well as plasma soluble P-, E- and L-selectins, indicating that activated platelets and endothelial cells may promote thrombus formation [Karakantza et al. 2004]. JAK2V617F+ endothelial cells have been found to contribute to clot formation in mice [Etheridge et al. 2014]. A high level of activated protein C resistance was recently found in ET patients with previous thrombosis [Brinkman et al. 2005]. Furthermore, an elevated level of circulating microparticles has been found in ET patients [Trappenburg et al. 2009]. All these findings indicate that the whole intravascular milieu of MPN patients presents a hypercoagulation state that needs to be further explored. On top of these ET-related disturbances, there are inherited factors with special importance in ET that are independent risk factors for thrombosis such as thrombophilic single nucleotide polymorphisms (SNPs) in genes of Factor VII [Buxhofer-Ausch et al. 2014]. As patients on aspirin still get thrombosis, it has been challenged whether the thromboxane inhibition produced by low dose aspirin is sufficient, and data supporting this view have been repor-ted [Dragani et al. 2010; Pascale et al. 2012].