JAK2V617F Mutation and Thrombosis History Are Determinants of Mean Platelet Volume (MPV) in Essential Thrombocythemia Patients
Authors: Marchetti Marina , Verzeroli Cristina , Giaccherini Cinzia , Gamba Sara , Vignoli Alfonso , Russo Laura , Finazzi Guido , Rambaldi Alessandro , Falanga Anna 
Published: October 2019

Abstract
Introduction and aim: Persistently enhanced platelet activation has been described in patients with myeloproliferative neoplasms, i.e. essential thrombocythemia (ET) and polycythemia vera (PV), which carry a high thrombotic risk. Different studies suggest that mean platelet volume (MPV) and immature platelet fraction (IPF) can serve as useful markers of platelet activation and increased thrombosis rate in various diseases. In a previous study of ET and PV patients, we demonstrated that JAK2V617F mutation and hydroxyurea (HU) treatment determine the IPF parameters (Panova-Noeva et al, Blood 2011). In this study of ET patients, we aimed to investigate on whether MPV values are influenced by pathogenic factors, such as JAK2V617F mutation, previous thrombotic events, HU treatment, and features of platelet activation.
Methods: Eighty-nine consecutive patients with ET (56F/33M; median age 60 yrs) were recruited after written informed consent. Venous blood samples were collected at enrollment and clinical data recorded. Ninety healthy subjects acted as a control group. The mutational status was as follows: 46 patients (51.6%) were JAK2V617F+, 23 (25.8%) CALR+, and 3 (3.4%) MPL+. Thirty eight patients were receiving HU cytoreductive therapy plus ASA, 6 patients HU alone, and 20 patients none of these drugs. Fifteen patients (16.8%) had a positive history of thrombosis. MPV was measured by an automated hematology analyzer (CELL-DYN Ruby System). Platelet surface P-selectin was measured by flow cytometry. Plasma levels of platelet-released proteins, i.e. soluble (s)P-selectin, sGPV, PF4, βTG, were measured by commercial ELISA (Stagò, France).
Results: The study shows that in ET patients, the MPV values were inversely related to platelet count (p=0.005, by a multivariate analysis). The analysis according to mutational status indicates that MPV was greater in JAK2V617F+ carriers compared to JAK2 wild type (p<0.05) or other mutation carriers. In addition, MPV was greater in subjects with a positive history of thrombosis versusthose without (p<0.05) and results remained significant after multivariate analysis (p<0.05). Differently, HU treatment did not correlate with MPV values. Also, the platelet activation parameters, including the levels of platelet surface P-selectin and the plasma circulating markers, i.e. sP-selectin, sGPV, PF4, βTG, showed no relation with MPV.
Conclusions: Our data provide evidence that the presence of JAK2V617F mutation or of a positive history of thrombosis are linked to MPV values in ET patients, which might contribute to the prothrombotic phenotype in these patients. In view of the increasing importance of MPV as a marker of platelet reactivity, prospective studies are warranted to evaluate the usefulness of MPV as a cellular marker to predict thrombosis in MPN patients.
Project funded by "AIRC-IG2013" grant Nr. 14505 from the "Italian Association for Cancer Research" (A.I.R.C.).

Disclosures
Falanga: Pfizer: Speakers Bureau; Aspen: Speakers Bureau; Janssen: Speakers Bureau.