SEARCH:   Advanced

Blood First Edition Paper, prepublished online November 3, 2009; DOI 10.1182/blood-2009-08-236679. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Dragani, A. Articles by Rocca, B. PubMed PubMed Citation Articles by Dragani, A. Articles by Rocca, B. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 5, 2009; accepted October 2, 2009. The contribution of cyclooxygenase-1 and -2 to persistent thromboxane biosynthesis in aspirin-treated essential thrombocythemia: implications for antiplatelet therapy Alfredo Dragani1, Silvia Pascale1, Antonio Recchiuti2, Domenico Mattoscio3, Stefano Lattanzio2, Giovanna Petrucci4, Luciana Mucci4, Elisabetta Ferrante2, Aida Habib5, Franco O. Ranelletti6, Giovanni Ciabattoni7, Giovanni Davi2, Carlo Patrono4 and Bianca Rocca4,7 1 Department of Hematology, 'Spirito Santo' Hospital, Pescara, Italy; 2 Center of Excellence on Aging, "G. D'Annunzio" University Foundation, Chieti, Italy; 3 Department of Biomedical Sciences, University "G. D'Annunzio", Chieti, Italy; 4 Department of Pharmacology, Catholic University School of Medicine, Rome, Italy; 5 Department of Biochemistry, American University of Beirut, Beirut, Lebanon; 6 Department of Pathology, Catholic University School of Medicine, Rome, Italy; 7 Department of Drug Sciences, School of Pharmacy, University "G. D'Annunzio", Chieti, Italy * Corresponding author; email: b.rocca{at}tiscali.it Abstract We tested whether cyclooxygenase (COX)-2 expression and unacetylated COX-1 in newly-formed platelets, might contribute to persistent thromboxane (TX) biosynthesis in aspirin-treated essential thrombocythemia (ET). Forty-one patients on chronic aspirin (100 mg/day) and 24 healthy subjects were studied. Platelet COX-2 expression was significantly increased in patients and correlated with tiazole orange-positive platelets (r=0.71, p<0.001). The rate of TXA2 biosynthesis in vivo, as reflected by urinary 11-dehydro TXB2 (TXM) excretion, and the maximal biosynthetic capacity of platelets, as reflected by serum TXB2 were higher in patients as compared to aspirin-treated healthy volunteers. Serum TXB2 was significantly reduced by the selective COX-2 inhibitor, NS-398, added in vitro. Patients were randomized to adding the selective COX-2 inhibitor, etoricoxib, or continuing aspirin for 7 days. Etoricoxib significantly reduced by approximately 25% TXM excretion and serum TXB2. Fourteen of the 41 patients were studied again 21±7 months after first visit. Serum TXB2 was consistently reduced by approximately 30% by adding NS398 in vitro, while it was completely suppressed 50µM aspirin. Accelerated platelet regeneration in the majority of aspirin-treated ET patients may explain aspirin-persistent TXA2 biosynthesis through enhanced COX-2 activity and faster renewal of unacetylated COX-1. These findings may help reassessing the optimal antiplatelet strategy in ET. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020