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

Giovanna Petrucci, Bianca Rocca, Luciana Mucci, Carlo Patrono, A Dragani, S Pascale, A Recchiuti, D Mattoscio, S Lattanzio, E Ferrante, A Habib, Fo Ranelletti, G Ciabattoni, G Davì

Risultato della ricerca: Contributo in rivistaArticolo in rivista

84 Citazioni (Scopus)

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 TXA(2) biosynthesis in vivo, as reflected by urinary 11-dehydro-TXB(2) (TXM) excretion, and the maximal biosynthetic capacity of platelets, as reflected by serum TXB(2), were higher in patients compared with aspirin-treated healthy volunteers. Serum TXB(2) 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 TXB(2). Fourteen of the 41 patients were studied again 21 (+/- 7) months after the first visit. Serum TXB(2) was consistently reduced by approximately 30% by adding NS398 in vitro, while it was completely suppressed with 50 microM aspirin. Accelerated platelet regeneration in most aspirin-treated ET patients may explain aspirin-persistent TXA(2) 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.
Lingua originaleEnglish
pagine (da-a)1054-1061
Numero di pagine8
RivistaBlood
Volume115
DOI
Stato di pubblicazionePubblicato - 2010

Keywords

  • Adult
  • Aspirin
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Cyclooxygenase Inhibitors
  • Drug Therapy, Combination
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors
  • Pyridines
  • Sulfones
  • Thrombocythemia, Essential
  • Thromboxane A2
  • Thromboxane B2
  • Thromboxanes
  • Treatment Outcome

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