title: Nitric oxide derivatives and soluble plasma selectins in patients with myeloproliferative neoplasms.
abstract: 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/10(6) platelets) and PV (482 +/- 53 ng/10(6) platelets) patients compared to controls (120 +/- 8 ng/10(6) 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.
authors.affiliation: Division of Immunohematology and Transfusion Medicine & Hemostasis and Thrombosis Center, Ospedali Riuniti, Bergamo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cella
authors.forename: Marina
authors.initials: M
authors.lastname: Marchetti
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Vianello
authors.forename: Marina
authors.initials: M
authors.lastname: Panova-Noeva
authors.forename: Alfonso
authors.initials: A
authors.lastname: Vignoli
authors.forename: Laura
authors.initials: L
authors.lastname: Russo
authors.forename: Tiziano
authors.initials: T
authors.lastname: Barbui
authors.forename: Anna
authors.initials: A
authors.lastname: Falanga
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000494:pharmacology; D004252:DNA Mutational Analysis; D019040:E-Selectin / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009569:Nitric Oxide / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D019007:P-Selectin / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D011087:Polycythemia Vera / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013920:Thrombocythemia, Essential / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D000925:Anticoagulants; D019040:E-Selectin; D019007:P-Selectin; D009569:Nitric Oxide; D053614:Janus Kinase 2; D006918:Hydroxyurea