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Thromb Haemost 2010; 104(01): 151-156
DOI: 10.1160/TH09-09-0663
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

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

Giuseppe Cella
1   Cardiac, Thoracic and Vascular Sciences Dept, University of Padua, Padua, Italy
,
Marina Marchetti
2   Division of Immunohematology and Transfusion Medicine & Hemostasis and Thrombosis Center, Ospedali Riuniti, Bergamo, Italy
,
Fabrizio Vianello
1   Cardiac, Thoracic and Vascular Sciences Dept, University of Padua, Padua, Italy
,
Marina Panova-Noeva
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
,
Alfonso Vignoli
2   Division of Immunohematology and Transfusion Medicine & Hemostasis and Thrombosis Center, Ospedali Riuniti, Bergamo, Italy
,
Laura Russo
2   Division of Immunohematology and Transfusion Medicine & Hemostasis and Thrombosis Center, Ospedali Riuniti, Bergamo, Italy
,
Tiziano Barbui
4   Research Foundation, Ospedali Riuniti, Bergamo, Italy
,
Anna Falanga
2   Division of Immunohematology and Transfusion Medicine & Hemostasis and Thrombosis Center, Ospedali Riuniti, Bergamo, Italy
› Author Affiliations Financial support: This study was supported in part by grants from the “Associazione Italiana per la Ricerca sul Cancro (AIRC)”, and from the NIH Myeloproliferative Disorders Research Consortium, to A.F.
Further Information

Publication History

Received: 24 September 2009

Accepted after major revision: 26 February 2010

Publication Date:
23 November 2017 (online)

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Summary

Essential thrombocythaemia (ET) and polycythaemia vera (PV) are characterised by a high incidence of thrombotic complications due to highshear 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 NOMX levels could represent an additional antithrombotic mechanism of this drug.

Keywords

Nitric oxide - selectins - essential thrombocythemia - polycythemia vera - Hydroxyurea
 

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