Mohamed Hussam Aswad

The clinical course of essential thrombocythemia (ET) is complicated with thrombosis which significantly impacts patients’ mortality. Studies have identified JAK2^V617F mutation as an independent risk factor for thrombosis. Circulating extracellular vesicles (EVs) were evaluated in several studies regarding myeloproliferative neoplasms and thrombosis as potential biomarkers. The present study investigates the relationship between JAK2^V617F mutation and EVs levels in 119 ET patients. Our analyses revealed that JAK2^V617F-positive patients are at a significantly increased risk of thrombosis within five years before the ET diagnosis (hazard ratio [95% CI]: 11.9 [1.7–83.7], P = 0.013), and that JAK2^V617F mutation is an independent risk factor for thrombosis at ET diagnosis or during the follow-up (hazard ratio [95% CI]: 3.56 [1.47–8.62], P = 0.005). ET patients have higher levels of platelet-EVs, erythrocyte-EVs and procoagulant activity of EVs than the healthy population. Absolute and relative counts of platelet-EVs are increased in the presence of JAK2^V617F mutation ( P = 0.018, P = 0.024, respectively). In conclusion, our results support the role of JAK2^V617F mutation in the pathogenesis of thrombosis in essential thrombocythemia through enhancing platelet activation.

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 platelet- and 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 >400×10⁹/l, hematocrit >45%, or leukocytes >10×10⁹/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.