RESUMEN
BACKGROUND: Optimal anti-thrombotic therapy for acute coronary syndromes (ACS) should suppress pro-thrombotic activity at the site of plaque rupture. We sought to determine whether platelet reactivity is increased in blood in the immediate vicinity of a ruptured plaque and is apparent even when blood is obtained by sampling from a catheter placed proximal to the lesion. METHODS: Blood was obtained from a catheter placed in the aorta and from the same catheter after engaging the culprit coronary artery. Platelet reactivity was determined with the use of flow cytometry by surface expression of P-selectin. RESULTS: In preliminary studies we demonstrated that a marker of thrombin activity, fibrinopeptide A, was similarly increased in blood taken from the coronary sinus and coronary arterial ostium of patients with ACS. Subsequently blood was obtained from the aorta and coronary arterial ostium through a coronary guide catheter for assessment of platelet reactivity in 23 subjects with ACS and 22 subjects with stable angina. The percentage of platelets expressing P-selectin in response to 0.2 microM adenosine diphosphate (ADP) was greater in coronary arterial samples from patients with ACS (aorta=6.1+/-1%, coronary artery=8.8+/-1.6%, p=0.02) compared with that in patients with stable symptoms (aorta=6.9+/-1.2, coronary artery=6.5+/-1.4, p=NS). CONCLUSIONS: Coronary arterial blood obtained from the ostium through a coronary guide catheter can be used to determine whether thrombin activity and platelet reactivity are increased in the immediate vicinity of a ruptured atherosclerotic plaque. The simplicity of the approach developed should facilitate its use in future studies designed to determine the impact of optimal suppression of platelet reactivity and the pro-thrombotic state before coronary interventions on short- and long-term clinical outcomes.
Asunto(s)
Enfermedad de la Arteria Coronaria/complicaciones , Circulación Coronaria , Activación Plaquetaria , Rotura Espontánea/sangre , Enfermedad Aguda , Anciano , Aorta , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/patología , Vasos Coronarios , Fibrinolíticos/administración & dosificación , Fibrinopéptido A/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Selectina-P/sangre , Activación Plaquetaria/efectos de los fármacos , Rotura Espontánea/etiología , Trombofilia/sangre , Trombofilia/etiologíaRESUMEN
BACKGROUND: Platelet activation is pivotal in the pathogenesis of complications after percutaneous coronary interventions (PCI). We previously reported substantial interindividual variability in activation of glycoprotein (GP) IIb/IIIa in response to a low concentration of ADP. We assessed GP IIb/IIIa activation prospectively to determine whether this could differentiate patients at low risk from those at high risk for complications early and late after PCI. Methods and Results-- A total of 112 patients undergoing PCI were studied. Platelet reactivity was determined with the use of flow cytometry. Patients were classified into high and low platelet reactivity groups on the basis of extent of activation of GP IIb/IIIa in response to 0.2 micromol/L ADP. The median value was used for differentiation. The incidence during 90-day follow-up interval of a composite end point (myocardial infarction, urgent revascularization, or repeat revascularization) was determined in each group. Follow up was completed in all 112 patients. The 2 groups were similar with respect to diverse clinical characteristics. Nevertheless, the incidence of the composite end point occurred in 26.8% of the high and 7.1% in the low platelet reactivity group (P=0.01). The difference in the composite end point was most striking during the 30- to 90-day interval after PCI (16.7% versus 1.9%; P=0.02). Repeat revascularization was more frequent in those with increased platelet reactivity (17.9% versus with 3.6%, P=0.029). CONCLUSIONS: Prospective assessment of platelet GP IIb/IIIa activation permits stratification of patients into low- and high-risk groups with respect to adverse events after PCI.