Platelet anaesthesia during extracorporeal circulation: differential effects of GP IIb/IIIa blockers on platelet activation marker P-selectin expression at hypothermia.
Thromb Res
; 122(3): 383-9, 2008.
Article
em En
| MEDLINE
| ID: mdl-18304613
ABSTRACT
INTRODUCTION:
Blood contact with artificial surfaces of extracorporeal circulation (ECC) and hypothermia as applied in cardiac surgery cause platelet dysfunction possibly followed by bleeding complications. "Platelet anaesthesia" is a pharmacological strategy to protect platelets against ECC-induced damage using a GP IIb/IIIa blocker, which should be short acting to achieve maximal therapy control thereby avoiding post-ECC haemorrhage. However, GP IIb/IIIa blockers can paradoxically induce platelet activation, which may limit their efficiency as anti-platelet drugs. This in-vitro study investigated potentially platelet-activating effects of short-acting GP IIb/IIIa blockers during normothermic and hypothermic ECC. MATERIALS ANDMETHODS:
Control (untreated) and treated (using either FK633 [half-life 0.52 h], tirofiban [half-life 1.5-2 h], or eptifibatide [half-life 1.5 h]) heparinized blood was circulated in an ECC-model at normothermia (37 degrees C) and hypothermia (18 degrees C). Percentages of platelet aggregates and P-selectin-expressing (activated) platelets, platelet-counts and Thrombin-Antithrombin (TAT) complex formation were determined before (baseline) and after ECC. Statistical analysis was performed using multifactorial ANOVA after log-transforming the data.RESULTS:
GP IIb/IIIa blockade inhibited ECC-induced platelet aggregation and platelet loss and decreased P-selectin expression at normothermia. During hypothermic ECC P-selectin was decreased by tirofiban but augmented by FK633 and eptifibatide. TAT formation was only decreased by FK633.CONCLUSIONS:
Especially regarding its ultra-short half-life FK633 has the best properties for platelet protection during normothermic ECC. However, at hypothermia FK633 and eptifibatide induce platelet activation. In relation with "platelet anaesthesia" possible hypothermia-associated prothrombotic side effects of GP IIb/IIIa blockers should be considered.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plaquetas
/
Ativação Plaquetária
/
Complexo Glicoproteico GPIIb-IIIa de Plaquetas
/
Selectina-P
/
Dipeptídeos
/
Circulação Extracorpórea
/
Hipotermia Induzida
Tipo de estudo:
Prognostic_studies
Limite:
Humans
/
Male
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article