Circulating endothelial progenitor cells and residual in vivo thromboxane biosynthesis in low-dose aspirin-treated polycythemia vera patients

• Published in: Blood Vol. 112; no. 4; pp. 1085 - 1090
• Main Authors: Santilli, Francesca, Romano, Mario, Recchiuti, Antonio, Dragani, Alfredo, Falco, Angela, Lessiani, Gianfranco, Fioritoni, Francesca, Lattanzio, Stefano, Mattoscio, Domenico, De Cristofaro, Raimondo, Rocca, Bianca, Davì, Giovanni
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.08.2008; The Americain Society of Hematology
• Subjects: Adult; Aged; Aged, 80 and over; Arginine - analogs & derivatives; Arginine - blood; Aspirin - administration & dosage; Aspirin - pharmacology; Biological and medical sciences; Blood; Case-Control Studies; Colony-Forming Units Assay; Diseases of red blood cells; Endothelial Cells - drug effects; Endothelial Cells - pathology; Female; Hematologic and hematopoietic diseases; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Polycythemia Vera - blood; Polycythemia Vera - drug therapy; Polycythemias; Stem Cells - drug effects; Stem Cells - pathology; Thromboxane A2 - blood; Thromboxane B2 - blood; Thromboxanes - biosynthesis; Human; Prostaglandin-endoperoxide synthase; Endothelial cell; Hematology; Enzyme; Arachidonic acid derivatives; Stem cell; Low dose; Enzyme inhibitor; Polycythemia vera; Hemopathy; Biosynthesis; Acetylsalicylic acid; Antiplatelet agent; Myeloproliferative syndrome; In vivo; Treatment; Eicosanoid; Oxidoreductases; Salicylates; Thromboxane
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2007-11-123091

Polycythemia vera (PV) is associated with high morbidity and mortality for thrombosis. We hypothesized that in PV altered sensitivity to aspirin might be related to dysfunction of the endothelial repair and/or of the nitric oxide (NO) system. Urinary thromboxane (TX) A2 metabolite (TXM), endothelial colony-forming cells (ECFCs), plasma asymmetric dimethylarginine (ADMA) and von Willebrand factor (VWF) were measured in 37 PV patients on low-dose aspirin and 12 healthy controls. Patients showed an approximately 2-fold increase in median TXM and plasma ADMA levels (P < .001), while ECFC numbers were reduced by approximately 7-fold (P < .001) as compared with nonaspirinated control. These differences were more pronounced in patients with previous thrombosis. An 8-week course of aspirin did not affect ECFCs in 6 controls. VWF and TXM correlated directly with ADMA, and inversely with ECFCs. By multiple regression analysis, lower ECFC quartiles (beta = −0.39; SE = 0.17; P = .028) and higher VWF levels (beta = 0.338, SE = 0.002, P = .034) were independent predictors of higher TXM quartiles (R2 = 0.39). Serum TXB2, measured in 22 patients, was approximat-ly 10-fold higher than aspirin-treated controls. PV patients appear to have an unbalanced ECFC/NO axis, and an apparent altered sensitivity of platelet TXA2 production, all potentially contributing to aspirin-insensitive TXM formation. Thus, additional antithrombotic strategies may be beneficial in PV.