11 The rationale of these criteria was to create an interface bet

11 The rationale of these criteria was to create an interface between clinical and laboratory findings with morphological features and molecular/genetic (JAK2 V617F and other mutations) data with the aim to increase diagnostic sensitivity and specificity and to obtain readily applicable algorithms for routine clinical practice. Standard and uniform diagnostic criteria for Ph-negative classical MPN are essential for clinical research, case reporting, and clinical practice.

Currently, recommendations for management learn more of these MPN are adapted to the risk of arterial and venous thrombosis and are largely based on consensus of experts. 12 Despite the neoplastic nature of MPN, it is advisable to distinguish these disorders from leukemia, with this especially applying to PV and ET, associated with a life expectancy not substantially different MLN0128 from that of the general population. The concern regarding the possibility that MPN can be heritable should be clarified by reporting that the vast majority of MPN cases are sporadic and that the genetic mutation of JAK2 occurring in germ line cell has been reported in a single kindred with hereditary thrombocytosis.13 These are likely to be rare families but suggest that other germline JAK2 mutations will be detected. Patients should know that occasionally other members of the family may present these disorders, 14 indicating a predisposition

likely sustained by a genetic background revealed by haplotype 46/1 of the JAK2 gene. 15 Patients should know that both PV and ET are marked by thrombo-hemorrhagic

complications and a propensity to transform into myelofibrosis and acute leukemia and that the aim of therapy to prevent these complications needs to be balanced against the risks associated with the use of cytotoxic drugs. Moreover, other practical aspects, such as how to proceed in pregnancy or surgery, could also be discussed whenever applicable. 12 Because the current therapy in PV and ET is aimed at lowering Farnesyltransferase the risk of thrombosis, the risk classification system in these disorders is shaped according to thrombosis risk. Thrombosis is the most frequent clinical complication in ET and PV. In two randomized clinical trials in ET, the cumulative rates for major vascular complications during follow-up were 2.7 and 6.2 per 100 persons per year, respectively.[16] and [17] In the prospective European Collaboration on Low-dose Aspirin in Polycythemia (ECLAP) study, cardiovascular mortality accounted for 1.5 deaths per 100 persons per year and the cumulative rate of non-fatal thrombosis was 3.8 events per 100 persons per year.18 The most frequent types of major thrombosis include stroke, transient ischemic attack, myocardial infarction, peripheral arterial thrombosis and deep venous thrombosis often occurring in unusual sites, such as hepatic, portal and mesenteric veins.

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