The contribution of cyclooxygenase-1 and -2 to persistent thromboxane biosynthesis in aspirin-treated essential thrombocythemia: implications for antiplatelet therapy
In: Blood, Jg. 115 (2010-02-04), S. 1054-1061
Online
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Zugriff:
We tested whether cyclooxygenase 2 (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 thiazole orange–positive platelets (r = 0.71, P < .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 compared with 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 the first visit. Serum TXB2 was consistently reduced by approximately 30% by adding NS398 in vitro, while it was completely suppressed with 50μM aspirin. Accelerated platelet regeneration in most 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 in reassessing the optimal antiplatelet strategy in ET.
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The contribution of cyclooxygenase-1 and -2 to persistent thromboxane biosynthesis in aspirin-treated essential thrombocythemia: implications for antiplatelet therapy
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Autor/in / Beteiligte Person: | Pascale, Silvia ; Ciabattoni, Giovanni ; Dragani, Alfredo ; Mucci, Luciana ; Habib, Aida ; Recchiuti, Antonio ; Ranelletti, Franco O. ; Mattoscio, Domenico ; Ferrante, Elisabetta ; Lattanzio, Stefano ; Patrono, Carlo ; Rocca, Bianca ; Davì, Giovanni ; Petrucci, Giovanna |
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Zeitschrift: | Blood, Jg. 115 (2010-02-04), S. 1054-1061 |
Veröffentlichung: | American Society of Hematology, 2010 |
Medientyp: | unknown |
ISSN: | 1528-0020 (print) ; 0006-4971 (print) |
DOI: | 10.1182/blood-2009-08-236679 |
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