Abstract
Arterial (AT) and venous (VT) thrombotic events are the most common complications in patients with polycythemia vera (PV) and are the leading causes of morbidity and mortality. In this regard, the impact of JAK2V617F variant allele frequency (VAF) is still debated. The purpose of the current study was to analyze the impact of JAK2V617F VAF in the context of other established risk factors for thrombosis in a total of 865 2016 WHO-defined PV patients utilizing two independent cohorts: University of Florence (n = 576) as a training cohort and Policlinico Gemelli, Catholic University, Rome (n = 289) as a validation cohort. In the training cohort VT free-survival was significantly shorter in the presence of a JAK2V617F VAF > 50% (HR 4; p < 0.0001), whereas no difference was found for AT (HR 0.9; p = 0.8). Multivariable analysis identified JAK2V617F VAF > 50% (HR 3.8, p = 0.001) and previous VT (HR 2.2; p = 0.04) as independent risk factors for future VT whereas diabetes (HR 2.4; p = 0.02), hyperlipidemia (HR 2.3; p = 0.01) and previous AT (HR 2; p = 0.04) were independent risk factors for future AT. Similarly, JAK2V617F VAF > 50% (HR 2.4; p = 0.01) and previous VT (HR 2.8; p = 0.005) were confirmed as independent predictors of future VT in the validation cohort. Impact of JAK2V617F VAF > 50% on VT was particularly significant in conventional low-risk patients, both in Florence (HR 10.6, p = 0.005) and Rome cohort (HR 4; p = 0.02). In conclusion, we identified JAK2V617F VAF > 50% as an independent strong predictor of VT, supporting that AT and VT are different entities which might require distinct management.
Highlights
Polycythemia Vera (PV) is a Philadelphia-negative chronic myeloproliferative neoplasm (MPN) along with essential thrombocythemia, overt myelofibrosis (MF) and pre-fibrotic MF
The aim of the current study was to evaluate the impact of JAK2V617F variant allele frequency (VAF) at diagnosis on rate of arterial and venous thrombosis, in the context of other established risk factors, in 2016 WHO-defined PV patients belong to a training cohort collected from Center of Research and Innovation in Myeloproliferative Neoplasms (CRIMM), University of Florence, Italy and a validation cohort from Policlinico Gemelli, Catholic University, Rome, Italy
Considering the patients included in the Florence cohort we found that JAK2V617F VAF as a continuous variable was correlated with the risk of venous thrombosis after diagnosis (p = 0.003; HR 1; 95% CI 1–1.1) but not with arterial thrombosis (p = 0.8; HR 1; 95% CI 0.9–1)
Summary
Polycythemia Vera (PV) is a Philadelphia-negative chronic myeloproliferative neoplasm (MPN) along with essential thrombocythemia, overt myelofibrosis (MF) and pre-fibrotic MF. It is mainly characterized by clonal erythrocytosis associated with an increased risk of thrombo-hemorrhagic complications, progression to MF and, to lesser extent, transformation to acute myeloid leukemia (AML). Current management of PV relies on a two-tiered model that identifies patients at high-risk (age ≥ 60 years and/or history of cardiovascular events (CV)) and low-risk (absence of both risk factors) of thrombosis. The International Working Group on Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) identified prior arterial events and hypertension as risk factors for arterial thrombosis whereas prior venous events and age ≥65 years were identified as risk factors for venous thrombosis [4], pointing to arterial and venous thrombosis as two biologically different processes with distinct disease risk factors. Other studies focused on additional risk factors for thrombosis in PV including generic CV risk factors and leukocytosis [5, 6]
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