RESUMEN
BACKGROUND: High levels of glycoprotein (GP) IIb/IIIa receptor inhibition are required to prevent arterial thrombosis following percutaneous coronary intervention. Ex-vivo turbidometric platelet aggregation in citrate anticoagulated blood samples has been the primary method previously utilized to derive dose regimens for administering platelet GP IIb/IIIa inhibitors. Enhanced GP IIb/IIIa binding and inhibition of platelet aggregation for eptifibatide secondary to citrate induced reduction of ionized plasma calcium concentrations has been reported. METHODS/RESULTS: We evaluated the differential effects of citrate versus PPACK anticoagulation on turbidometric platelet inhibition in normal volunteers by eptifibatide, tirofiban or abciximab. The decrease in ionized calcium afforded by citrate was associated with enhanced in vitro platelet inhibition for all three GP IIb/IIIa inhibitors, including abciximab. The magnitude of citrate effect was greatest for eptifibatide. Both tirofiban and abciximab have similar citrate calcium chelation associated enhancement of measured platelet inhibition. CONCLUSION: Accurate assessment and comparison of platelet inhibition by GP IIb/IIIa inhibitors may require avoidance of calcium chelating anticoagulants.
Asunto(s)
Clorometilcetonas de Aminoácidos/farmacología , Antitrombinas/farmacología , Quelantes/farmacología , Ácido Cítrico/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Agregación Plaquetaria/efectos de los fármacos , Tirosina/análogos & derivados , Abciximab , Anticuerpos Monoclonales/farmacología , Anticoagulantes/farmacología , Recolección de Muestras de Sangre/métodos , Recolección de Muestras de Sangre/normas , Calcio/farmacología , Interacciones Farmacológicas , Monitoreo de Drogas/métodos , Monitoreo de Drogas/normas , Eptifibatida , Humanos , Fragmentos Fab de Inmunoglobulinas/farmacología , Péptidos/farmacología , Pruebas de Función Plaquetaria/normas , Tirofibán , Tirosina/farmacologíaRESUMEN
BACKGROUND: Plaque disruption with resultant platelet activation and leukocyte-platelet aggregation is a pathophysiologic process common to both acute coronary syndromes and percutaneous coronary interventions. Unfractionated heparin is a standard antithrombotic therapy in patients with both acute coronary syndromes and in those undergoing percutaneous coronary interventions. Low-molecular-weight heparins have been reported to cause less platelet activation than unfractionated heparin. METHODS: Monocyte-platelet aggregates, neutrophil-platelet aggregates, platelet surface P-selectin, and platelet surface glycoprotein (GP) IIIa were measured serially by whole blood flow cytometry in 40 patients with unstable angina (randomly assigned to either unfractionated heparin 70 U/kg or the low-molecular-weight heparin dalteparin 60 IU/kg) undergoing coronary intervention with planned abciximab administration (in 2, one-half-dose boluses). Assays were performed at baseline, 5 minutes after administration of either type of heparin, 10 minutes after the first bolus of abciximab, 10 minutes after second bolus of abciximab, and 8 to 10 and 16 to 24 hours after administration of either heparin. RESULTS: No significant differences in clinical outcomes were observed between patients receiving either unfractionated heparin or dalteparin. The number of circulating P-selectin-positive platelets was increased by unfractionated heparin but not dalteparin, and abciximab reversed this increase. The number of circulating P-selectin-positive platelets was reduced below baseline levels in both treatment groups 8 to 10 and 16 to 24 hours after study drug administration. At 8 to 10 and 16 to 24 hours after administration of study drug, platelet degranulation in response to iso-thrombin receptor agonist peptide 1.5 mmol/L was significantly reduced by almost 50% (compared with immediately after study drug administration). Both unfractionated heparin and dalteparin significantly increased the numbers of circulating monocyte-platelet and neutrophil-platelet aggregates, which were subsequently reduced to baseline levels after administration of the second abciximab bolus and to below baseline at both 8 to 10 and 16 to 24 hours in all patients. After both unfractionated heparin and dalteparin administration, platelet surface GP IIIa expression was significantly increased compared with baseline at both 8 to 10 and 16 to 24 hours. CONCLUSIONS: Dalteparin in combination with abciximab in patients with unstable angina undergoing coronary intervention appears to be safe. Unfractionated heparin, but not dalteparin, degranulates platelets in patients with unstable angina. Both heparins increase the number of circulating monocyte-platelet and neutrophil-platelet aggregates. Abciximab therapy during coronary interventions rapidly reduces the number of degranulated platelets and leukocyte-platelet aggregates.
Asunto(s)
Anticuerpos Monoclonales/farmacología , Antígenos CD/efectos de los fármacos , Enfermedad Coronaria/tratamiento farmacológico , Enfermedad Coronaria/cirugía , Dalteparina/farmacología , Dalteparina/uso terapéutico , Fibrinolíticos/uso terapéutico , Heparina/uso terapéutico , Fragmentos Fab de Inmunoglobulinas/farmacología , Leucocitos/química , Selectina-P/efectos de los fármacos , Agregación Plaquetaria/efectos de los fármacos , Glicoproteínas de Membrana Plaquetaria/efectos de los fármacos , Abciximab , Angioplastia Coronaria con Balón , Anticuerpos Monoclonales/uso terapéutico , Aterectomía , Fibrinolíticos/farmacología , Heparina/farmacología , Humanos , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Integrina beta3 , Leucocitos/efectos de los fármacos , Leucocitos/metabolismoRESUMEN
We encountered a case of systemic mast cell disease associated with rheumatoid factor; to our knowledge, this has not been reported in the literature. Rheumatoid arthritis as an unrelated second disease cannot be excluded, but there is support for a relation between joint symptoms, rheumatoid factor, and the mast cell disease.