E episodes in ET patients have been previously suggested. In moreE episodes in ET patients

E episodes in ET patients have been previously suggested. In more
E episodes in ET patients have been previously suggested. In more recent studies, a JAK2 gene dosage effect on granulocyte activation pattern was demonstrated in MPDs [49] along with, in ET, the activation of monocytes and platelet being more frequently observed in patients with a history of thrombosis [95]. In this last study, the JAK2 V617F mutation was found associated with the increased platelet activation. Clearly more information is needed regarding gene mutations and peripheral cells activation and their incidence on vasculo-occlusive complications.Hemorrhagic risk A risk of major hemorrhage of 0.33 patients/year during follow-up has been deducted from 21 previously published studies [50]. As already mentioned, severe hemorrhages were reported to be more PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28607003 common in patients with platelet count >1500 ?109/L but the risk decreases when platelet number is reduced by treatment, allowing the use of low dose aspirin associated to cytoreduction in these patients. In the ECLAP study of PV patients, a history of previous bleeding problems was also an important predictor of major hemorrhagia. Recently, a tentative categorization of the hemorrhagic risk has been proposed [56]:C/Low: in all the other cases.Risk of a clonal progression of ET ?progression or transformation into PV In ET patients, an increase of the Hb and Ht levels toward values observed in patients with primary erythrocytosis, or even a progression to a full-blown picture of PV (according to the PVSG criteria) has been observed in up to 5?.5 of large series of patients [96]. A critical revue of the criteria used at diagnosis to differentiate ET and PV may probably explain some of these apparent early progressions. The presence of EEC in BM cells, an increase level of PRV-1 mRNA in granulocytes and low circulating EPO levels in ET patients has already been proposed as an indication of a close relationship between PV and a subset of ET patients [35,38]. More recently, in a large prospective study of 806 ET patients it has been observed that progression to PV was restricted to patients with the JAK2 V617F mutation [47]. In this study, statistically higher Hb and circulating granulocytes levels, lower EPO values and hypercellular BM on biopsy material in JAK2 V617F positive-compared to JAK2 negative ET patients, suggested a continuum in mutated patients between ET and PV phenotypes. A statistically different rate of progression to a PV phenotype in JAK2 mutated ET patients was also observed in a retrospective study with a long term follow-up [92]. ?progression into myelofibrosis The risk of myelofibrotic transformation is shared by all Ph-negative MPDs diagnosed according to the PVSG criteria. Myelofibrosis itself is not a disease but rather a reaction pattern of the BM to cytokines released from the clonal proliferative cells in PV and IMF [97]. In ET (according to the PVSG criteria) myelofibrosis is a delayed event with a cumulative risk of occurrence estimated at 3 after 5 years, 8 after 10 years and 15 after 15 years [98]. No clear predictive factor of the risk in patients diagnosed according to the PVSG criteria has been published. According to the WHO classification based on BM biopsy findings, the risk of fibrotic progression has been estimated to 50 after a median follow-up of 38+/-30 GSK-AHAB chemical information months in IMF-0 or IMF-1 patients. In the description of IMF-0 and IMF-1, the degree of megakaryocyte dysplasia and the level of granulocyte hyperplasia are important features and may c.