The contribution of cyclooxygenase-1 and -2 to persistent thromboxane biosynthesis in aspirin-treated essential thrombocythemia: implications for antiplatelet therapy.
Blood
; 115(5): 1054-61, 2010 Feb 04.
Article
em En
| MEDLINE
| ID: mdl-19887674
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piridinas
/
Sulfonas
/
Tromboxanos
/
Aspirina
/
Ciclo-Oxigenase 1
/
Ciclo-Oxigenase 2
/
Trombocitemia Essencial
Tipo de estudo:
Clinical_trials
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Blood
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Itália