Details

Autor(en) / Beteiligte

• Dragani, Alfredo
• Pascale, Silvia
• Recchiuti, Antonio
• Mattoscio, Domenico
• Lattanzio, Stefano
• Petrucci, Giovanna
• Mucci, Luciana
• Ferrante, Elisabetta
• Habib, Aida
• Ranelletti, Franco O.
• Ciabattoni, Giovanni
• Davì, Giovanni
• Patrono, Carlo
• Rocca, Bianca

Titel

The contribution of cyclooxygenase-1 and -2 to persistent thromboxane biosynthesis in aspirin-treated essential thrombocythemia: implications for antiplatelet therapy

Ist Teil von

• Blood, 2010-02, Vol.115 (5), p.1054-1061

Ort / Verlag

Washington, DC: Elsevier Inc

Erscheinungsjahr

2010

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• 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.