Abstract Number: PB0452
Meeting: ISTH 2020 Congress
Background: ET is a myeloproliferative neoplasm characterized by a high rate of thrombotic complications. Our group has previously demonstrated that, in ET patients, TG-potential is increased, and neutrophils circulate in an activated status. Recent studies suggest that NETs can promote thrombus formation by several mechanisms, including TG induction.
Aims: In ET patients, we aimed to measure circulating levels of NETs and evaluate the influence on these levels of somatic mutations [i.e. JAK2V617F, Calreticulin (CalR)], and concomitant therapies. Furthermore, we aimed to assess whether a correlation may exist between plasma NETs levels and TG-potential.
Methods: Sixty-four ET patients (M/F: 27/37; median-age: 60 years) were analyzed: 35 JAK2V617F-positive and 19 CalR-positive; 26 on hydroxyurea+aspirin (HU+ASA), 5 on HU, and 20 on ASA therapy. Citrullinated Histone-DNA complexes were measured by an ELISA: results are expressed as ODx1000=mOD. TG was evaluated by the calibrated-automated-thrombogram (CAT) assay.
Results: ET patients displayed significantly higher NETs values compared to healthy controls (1,106±678 vs 635±423 mOD, p< 0.05). NETs inversely correlated with age: in ET patients, this correlation remained significant (p< 0.05) after correction for gender and therapies. ET CalR-positive patients (1,261±819 mOD; p< 0.05) showed significantly higher NETs levels compared to other subjects (JAK2V617F= 1,004±537 mOD; no mutations= 1,114±784 OD). After multivariate analyses corrected for gender, age and therapy, CalR mutation was still independently associated with elevated NETs. Significantly higher TG-potential was found in ET vs controls. High NETs levels were significantly (p< 0.05) associated with shorter time-to-peak and higher peak, also after correction for age, gender and HU therapy.
Conclusions: ET patients are characterized by elevated NETs and higher TG-potential, particularly in CalR-mutated subjects. We also demonstrate that NETs may significantly contribute to the ex-vivo increase of TG-potential in ET. Further studies are needed to assess the correlation between NETs levels and thrombotic risk.
To cite this abstract in AMA style:Gamba S, Tartari CJ, Herre M, Marchetti M, Russo L, Verzeroli C, Giaccherini C, Vignoli A, Olsson AK, Falanga A. Neutrophils Extracellular Traps (NETs) Contribute to Thrombin Generation (TG) Potential in Patients with Essential Thrombocythemia (ET) [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/neutrophils-extracellular-traps-nets-contribute-to-thrombin-generation-tg-potential-in-patients-with-essential-thrombocythemia-et/. Accessed September 24, 2023.
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