The Clinical Significance of Circulating Microparticles Concerning Thrombosis in BCR/ABL1-negative Myeloproliferative Neoplasms

Abstract

Background/Aim: This work aimed to prospectively evaluate the clinical significance of circulating microparticles (MPs) in relation to thrombotic risk factors and thrombotic complications in patients with BCR/ABL1-negative myeloproliferative neoplasms (MPN). Patients and Methods: In a cohort of 206 patients with MPN, MPs' procoagulant activity was measured by the Zymuphen functional assay in 429 samples, while plateletand erythrocyte-MPs were enumerated by flow cytometry in 558 samples. Results: MPN patients had higher MP levels than the control group. The levels of MPs were higher in male patients, smokers, and those who were older than 60 years, and in the presence of JAK2 V617F mutation, history of thrombosis, platelets >400×10 9 /l, hematocrit >45%, or leukocytes >10×10 9 /l. Cytoreductive treatment reduced MP levels, with anagrelide being associated with lower MP levels than hydroxyurea. Conclusion: The relationship with thrombotic risk factors indicates a possible role of MPs in the complex thrombotic mechanism, though cytoreductive treatment seems to affect this role through reducing MP levels.Circulating microparticles (MPs) are cell-derived vesicles ranging in size between 0.1 and 1 μm; are non-nucleated, have no synthetic capability, and contain a membrane skeleton with antigens indicating their cellular origin (1). Most commonly, MPs originate from platelets and megakaryocytes but also erythrocytes, leukocytes, endothelial cells, and tumor cells during activation or apoptosis (1, 2). MPs enhance coagulation by exposing the procoagulant anionic phosphatidylserine (PS) on their surface and/or expressing functional tissue factor (TF) (3). A higher level of MPs was detected in many pathological conditions, including autoimmune, hematological, cardiovascular, infectious, nephrological, and oncological disorders (1). BCR-ABL1 negative myeloproliferative neoplasms (MPN) belong to oncological disorders that have been linked to elevated levels of MPs (4-8).MPN are clonal myeloid disorders, including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Patients with MPN show excessive proliferation of hematopoietic precursors in the bone marrow leading to abundant levels of mature blood cells being released into the circulation (9). Thrombosis is a common complication of MPN that significantly impacts patients' mortality, accounting for the death of 33% of PV, 16% of ET, and 2% of PMF patients (10-12). Thrombosis may occur at venous, arterial, or microcirculatory sites and can be the first sign of MPN. Management of MPN is based on predicting the risk of thrombosis and starting treatment to prevent complications in vulnerable patients (13). Thus, identifying prognostic factors is the initial step in MPN patients. Thrombosis in MPN has been linked to higher MPs levels, and utilization of MPs as a surrogate biomarker of thrombosis has been suggested (6,8,14). Patients and Methods Patients. Analyses of MPs were conducted in a cohort of 206 patients diagnosed with BCR/ABL1-negativ...

Extracellular Vesicles in Haematological Disorders: A Friend or a Foe?

“…Significantly increased levels of EVs were noted in the plasma of patients compared to healthy individuals. Moreover, the increased EV levels were positively correlated with the presence of thrombotic risk factors, whereas a decrease both in the EV levels and the thrombotic events was noticed with the application of cytoreductive therapy, implying an association between the two [ 73 ]. However, the source of EVs was not defined, and neither was the presence of other contributing procoagulant factors.…”