Distinct yet complementary mechanisms of heparin and glycoprotein IIb/IIIa inhibitors on platelet activation and aggregation: implications for restenosis during percutaneous coronary intervention.

Day, J R S; Malik, I S; Weerasinghe, A; Poullis, M; Nadra, I; Haskard, D O; Taylor, K M; Landis, R C

Day, J R S; Malik, I S; Weerasinghe, A; Poullis, M; Nadra, I; Haskard, D O; Taylor, K M; Landis, R C.

Afiliación

Day JR; British Heart Foundation Cardiovascular Medicine and Cardiac Surgery Unit, National Heart and Lung Institute, Imperial College School of Medicine, Hammersmith Hospital, Du Cane road, London W12 0NN, UK. j.day@imperial.ac.uk

Heart ; 90(7): 794-9, 2004 Jul.

Article en En | MEDLINE | ID: mdl-15201252

RESUMEN

OBJECTIVE: To study the effect of unfractionated heparin (UFH) versus low molecular weight heparin (LMWH) in combination with glycoprotein (Gp) IIb/IIIa blockers on platelet activation and aggregation. METHODS: Washed platelets were stimulated with thrombin in the presence or absence of UFH (monoparin), LMWH (enoxaparin), and a Gp IIb/IIIa blocker (abciximab, eptifibatide, or tirofiban). RESULTS: Although Gp IIb/IIIa antagonists blocked the final common pathway of thrombin induced platelet aggregation, UFH and LMWH were better at blocking upstream platelet activation. UFH was significantly more effective than LMWH at inhibiting P selectin expression (p = 0.001) and platelet derived growth factor release from thrombin activated platelets (p = 0.012). CONCLUSIONS: UFH and LMWH exert complementary effects to Gp IIb/IIIa blockers by inhibiting afferent pathways of platelet activation. Coadministration of heparin with Gp IIb/IIIa blockers provides improved protection against persistent platelet activation, thereby improving outcome after percutaneous coronary intervention. Judging from these data, UFH may be more effective in this regard than LMWH, at least in vitro. The use of LMWH in preference to UFH during percutaneous coronary intervention, although initially attractive, may inadequately protect against platelet activation despite the presence of Gp IIb/IIIa blockers.

Asunto(s)

Anticoagulantes/farmacología; Hemostáticos/farmacología; Heparina/farmacología; Activación Plaquetaria/efectos de los fármacos; Inhibidores de Agregación Plaquetaria/farmacología; Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores; Trombina/farmacología; Tirosina/análogos & derivados; Abciximab; Angioplastia Coronaria con Balón; Anticuerpos Monoclonales/farmacología; Reestenosis Coronaria/sangre; Enoxaparina/administración & dosificación; Enoxaparina/farmacología; Eptifibatida; Citometría de Flujo; Heparina/administración & dosificación; Humanos; Fragmentos Fab de Inmunoglobulinas/farmacología; Péptidos/farmacología; Agregación Plaquetaria/efectos de los fármacos; Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/administración & dosificación; Glicoproteínas de Membrana Plaquetaria/antagonistas & inhibidores; Receptores Acoplados a Proteínas G/antagonistas & inhibidores; Tirofibán; Tirosina/farmacología

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tirosina / Inhibidores de Agregación Plaquetaria / Hemostáticos / Heparina / Trombina / Activación Plaquetaria / Complejo GPIIb-IIIa de Glicoproteína Plaquetaria / Anticoagulantes Límite: Humans Idioma: En Revista: Heart Asunto de la revista: CARDIOLOGIA Año: 2004 Tipo del documento: Article Pais de publicación: Reino Unido

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