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

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1054-1061
Number of pages8
JournalBlood
Volume115
Issue number5
DOIs
Publication statusPublished - Feb 4 2010

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Fingerprint Dive into the research topics of 'The contribution of cyclooxygenase-1 and -2 to persistent thromboxane biosynthesis in aspirin-treated essential thrombocythemia: Implications for antiplatelet therapy'. Together they form a unique fingerprint.

Cite this