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Nitric oxide derivatives and soluble plasma selectins in patients with myeloproliferative neoplasms

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
Topic:

Stem cells in cardiovascular biology and medicine

DOI: https://doi.org/10.1160/TH09-09-0663
Issue: 2010: 104/1 (July) pp. 1-190
Pages: 151-156

Nitric oxide derivatives and soluble plasma selectins in patients with myeloproliferative neoplasms

G. Cella (1), M. Marchetti (2), F. Vianello (1), M. Panova-Noeva (2, 3), A. Vignoli (2), L. Russo (2), T. Barbui (4), A. Falanga (2)

(1) Cardiac, Thoracic and Vascular Sciences Dept, University of Padua, Padua, Italy; (2) Division of Immunohematology and Transfusion Medicine & Hemostasis and Thrombosis Center, Ospedali Riuniti, Bergamo, Italy; (3) Department of Biochemistry, Laboratory for Clinical Thrombosis and Haemostasis, Maastricht University, Netherlands; (4) Research Foundation, Ospedali Riuniti, Bergamo, Italy

Keywords

Hydroxyurea, essential thrombocythemia, polycythemia vera, nitric oxide, selectins

Summary

Essential thrombocythaemia (ET) and polycythaemia vera (PV) are characterised by a high incidence of thrombotic complications due to high-shear stress of the vessel wall, blood hyperviscosity and hypoxaemia, all factors responsible for chronic endothelial dysfunction and platelet and leukocyte activation. We evaluated the activation status of vascular cells in 18 consecutive ET and 14 PV patients by measuring the plasma levels of the nitric oxide derivatives (NOX) (i.e. nitrites and nitrates) and of soluble selectins of platelet (P-selectin), endothelial cell (P-selectin and E-selectin) and leukocyte (L-selectin) origin. The effect of hydroxyurea (HU) therapy on these parameters was also investigated. NOX were significantly (p<0.01) increased in ET patients treated with HU (11.5 ± 2.6 nM) compared to non-HU treated ET (1.41 ± 0.3 nM) and to controls (4.78 ± 2.49 nM). Multivariate analysis confirmed HU therapy as an independent predictor of higher NOX levels in ET. In addition, NOX significantly correlated with haematocrit. Plasma P-selectin was significantly elevated in ET (350 ± 40 ng/106 platelets) and PV (482 ± 53 ng/106 platelets) patients compared to controls (120 ± 8 ng/106 platelets). In PV, also E-selectin (23.8 ± 4.2 ng/ml) was significantly increased compared to controls (11.2 ± 1.1 ng/ml; p<0.01). P-selectin was significantly correlated to platelet (R=0.33; p=0.01) and leukocyte count (R=0.6; p=0.000), while E-selectin (R=0.34; p=.014) and sL-selectin (R=0.3; p=0.03) were correlated with leukocyte count only. In the multivariate analysis, NOX predicted increased levels of E-selectin in ET, but not in PV patients. Our data demonstrate that ET and PV are characterised by an altered pattern of soluble selectins and NOX. HU-mediated increase of NOX levels could represent an additional antithrombotic mechanism of this drug.

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