RESUMEN
PURPOSE: We present a unique case of delayed-onset, profound eptifibatide-induced thrombocytopenia that occurred 5 days after initiation of the drug. SUMMARY: Eptifibatide is a platelet glycoprotein IIb/IIIa receptor inhibitor with indications for use in patients with acute coronary syndromes. Eptifibatide-induced thrombocytopenia is uncommon but well studied and typically occurs within 24 hours of initiation of the drug. In the case described here, a 62-year-old male with a past history of coronary artery disease (including percutaneous coronary intervention within the past 12 months) was started on eptifibatide at a dosage of 2 µg/kg per minute for management of significant thrombus burden prior to a planned cardiac revascularization procedure; heparin for anticoagulation was also initiated. About 5 days after initiation of eptifibatide, the patient developed severe thrombocytopenia, with the platelet count dropping precipitously from 249 × 103/µL on admission to less than 1 × 103/µL. After eptifibatide and heparin therapy were discontinued and the patient was switched to argatroban, the platelet count recovered to 38 × 103/µL over the next 2 days. An eptifibatide platelet antibody assay was positive for IgG-mediated reactions consistent with eptifibatide-induced thrombocytopenia. Scoring of this case with the Naranjo scale yielded a score of 4, suggesting a possible adverse reaction to eptifibatide. CONCLUSION: This is the first published case report of profound eptifibatide-induced thrombocytopenia occurring more than 24 hours after eptifibatide initiation and serves to bring awareness that a delayed reaction can occur.
Asunto(s)
Trombocitopenia , Masculino , Humanos , Persona de Mediana Edad , Eptifibatida/efectos adversos , Trombocitopenia/inducido químicamente , Trombocitopenia/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria , Recuento de Plaquetas , Heparina/efectos adversosRESUMEN
RATIONALE: Eptifibatide is an antiplatelet agent used in the medical management of acute coronary syndrome. Although multiple studies did not reveal a significant association between eptifibatide and the development of thrombocytopenia, recent case reports brought attention to this relatively rare side effect. PATIENT CONCERNS: We report a 61 years old male with acute coronary syndrome who underwent primary coronary intervention. DIAGNOSIS AND INTERVENTION: The patient developed acute profound thrombocytopenia following eptifibatide administration. Following prompt offending drug discontinuation, the platelet counts recovered, without clinical sequelae or the need for platelet transfusion. Dual antiplatelet therapy with aspirin and clopidogrel was resumed after platelet count normalization. OUTCOMES: The patient had a normal platelet count and no bleeding events on follow-up after three months upon discharge. CONCLUSION: Eptifibatide, a glycoprotein IIa/IIIb inhibitor used in the management of acute coronary syndrome, can induce acute, profound thrombocytopenia that can have significant morbidity in patients. This case highlights this relatively rare side effect and the importance of monitoring blood counts and observing for any signs of bleeding or thrombosis that might occur in such patients.
Asunto(s)
Síndrome Coronario Agudo , Trombocitopenia , Humanos , Masculino , Persona de Mediana Edad , Eptifibatida/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Clopidogrel/efectos adversos , Síndrome Coronario Agudo/tratamiento farmacológico , Trombocitopenia/diagnóstico , Aspirina/efectos adversos , Hemorragia/inducido químicamente , Glicoproteínas/efectos adversosRESUMEN
BACKGROUND: Early revascularization of the extracranial internal carotid artery in acute anterior circulation ischemic stroke (ACIS) is feasible and may improve clinical outcome. When a stent is deployed, antithrombotic agents should be administered peri-procedurally to ensure stent patency. Our institution implemented a protocol for the use of eptifibatide as a means of maintaining stent patency in the treatment of ACIS associated with cervical internal carotid artery occlusion. METHODS: Our internal database was queried for patients who received emergent endovascular therapy (ET) for ACIS with stent placement and eptifibatide administration between July 2016 and 2019. RESULTS: Twenty nine patients met the study criteria. The etiology was large artery atherosclerosis in 26 cases. Two patients had a dissection (7%), and one had a carotid occlusion related to a recent carotid endarterectomy. Mean NIHSS was 14. Sixteen patients received IVrtPA. Extracranial-intracranial tandem occlusion (TO) was present in 21 of cases. All patients received an eptifibatide bolus followed by an infusion for approximately 24 hours post stent deployment. Head CT was obtained prior to initiation of oral dual antiplatelet therapy with aspirin and clopidogrel. Successful recanalization was achieved in all patients with no evidence of downstream embolization. Symptomatic intracerebral hemorrhage occurred in one patient. Stent occlusion occurred in two patients, only one of which was symptomatic. Favorable clinical outcome with mRS ≤ 2 at 3 months was achieved in seventeen patients. CONCLUSIONS: The use of eptifibatide post procedure was associated with low risk of symptomatic intracranial hemorrhage, including in patients treated with rtPA.
Asunto(s)
Isquemia Encefálica/terapia , Estenosis Carotídea/terapia , Procedimientos Endovasculares/instrumentación , Eptifibatida/administración & dosificación , Fibrinolíticos/administración & dosificación , Inhibidores de Agregación Plaquetaria/administración & dosificación , Stents , Accidente Cerebrovascular/terapia , Anciano , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/etiología , Estenosis Carotídea/complicaciones , Estenosis Carotídea/diagnóstico por imagen , Bases de Datos Factuales , Urgencias Médicas , Procedimientos Endovasculares/efectos adversos , Eptifibatida/efectos adversos , Femenino , Fibrinolíticos/efectos adversos , Humanos , Hemorragias Intracraneales/inducido químicamente , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/etiología , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Antígenos de Plaqueta Humana/inmunología , Autoanticuerpos/inmunología , Eptifibatida/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Púrpura Trombocitopénica Idiopática/etiología , Infarto del Miocardio con Elevación del ST/sangre , Trombosis/etiología , Arginina/análogos & derivados , Arginina/uso terapéutico , Aspirina/uso terapéutico , Terapia Combinada , Trombosis Coronaria/etiología , Trombosis Coronaria/cirugía , Sustitución de Medicamentos , Quimioterapia Combinada , Eptifibatida/inmunología , Eptifibatida/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea , Ácidos Pipecólicos/uso terapéutico , Inhibidores de Agregación Plaquetaria/inmunología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/inmunología , Transfusión de Plaquetas , Púrpura Trombocitopénica Idiopática/inmunología , Púrpura Trombocitopénica Idiopática/terapia , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/terapia , Choque Cardiogénico/etiología , Stents/efectos adversos , Sulfonamidas/uso terapéutico , Trombectomía , Terapia Trombolítica , Trombosis/tratamiento farmacológico , Ticagrelor/uso terapéutico , Warfarina/uso terapéuticoRESUMEN
The present study aimed to evaluate the pharmacokinetic properties and antiplatelet aggregation activity of eptifibatide in healthy Chinese subjects. Eptifibatide (180 µg/kg) was administrated by 2 bolus injections 10 minutes apart, followed by a 2.0 µg/kg/min infusion for 24 hours. The eptifibatide pharmacokinetic and antiplatelet aggregation activities were evaluated using nonlinear mixed-effects modeling and noncompartmental analysis. Safety assessments included adverse events, hematology, and biochemistry tests. Twelve Chinese healthy subjects were enrolled and completed the study. Steady-state concentrations were achieved at 0.5 to 24 hours after dosing. The median time to maximum concentration was 13 minutes, and the mean terminal elimination half-life was 148.19 minutes. The effective inhibition of platelet aggregation (<20% platelet aggregation) occurred by 3 minutes after starting dosing to 4 hours after termination of the infusion. Eptifibatide concentrations were fitted with a 3-compartment model, and the typical value of clearance was 0.11 L/min, with no significant covariates found. Three mild adverse events were detected in the study. Eptifibatide displays high sensitivity and excellent tolerability in healthy Chinese subjects. The dosage of eptifibatide recommended on the label for whites can effectively inhibit platelet aggregation.
Asunto(s)
Eptifibatida/farmacocinética , Inhibidores de Agregación Plaquetaria/farmacocinética , Agregación Plaquetaria/efectos de los fármacos , Pruebas de Función Plaquetaria/métodos , Pueblo Asiatico/etnología , Índice de Masa Corporal , Eptifibatida/administración & dosificación , Eptifibatida/efectos adversos , Femenino , Semivida , Voluntarios Sanos , Humanos , Infusiones Intravenosas , Masculino , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Seguridad , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Monitoring anticoagulation with activated clotting time (ACT) has been proposed to reduce ischemic or bleeding events. However, the value of using ACT to improve outcomes is uncertain. This study sought to determine the relationship between ACT and outcomes during percutaneous coronary intervention in patients with non-ST-segment-elevation acute coronary syndrome (NSTE-ACS) treated by unfractionated heparin with GPIs (glycoprotein IIb/IIIa inhibitors). METHODS AND RESULTS: From the randomized TAO trial (Treatment of Acute Coronary Syndromes With Otamixaban), we analyzed the value of ACT to predict ischemic and bleeding outcomes in the 3275 patients receiving unfractionated heparin plus eptifibatide. Ischemic and safety outcomes were analyzed according to ACT to determine the best threshold. Median peak ACT was 225 s. There was no correlation (r=-0.02; P=0.24) between the unfractionated heparin dose received and the ACT value before percutaneous coronary intervention. There was no evidence of a nonlinear association between ACT and either ischemic or bleeding events (P=0.66; P=0.07). No threshold was found to predict ischemic complications. Conversely, increased bleeding was observed with ACT >230 s with an optimal threshold of ACTs ≥250 s (4.53% versus 6.17%; odds ratio, 1.46; 95% confidence interval, 1.04-2.06; P=0.028). This optimal threshold varied according to access site: ≥250 s (6.86% versus 10.18%; odds ratio, 1.57; 95% confidence interval, 1.00-2.45; P=0.047) by femoral approach and ≥290 s (2.86% versus 5.43%; odds ratio, 2.24; 95% confidence interval, 1.05-4.44; P=0.027) by radial approach. CONCLUSIONS: In the TAO trial, peak procedural ACT ≥250 s was associated with increased bleeding risk in non-ST-segment-elevation acute coronary syndrome patients treated with unfractionated heparin plus GPIs. This threshold was increased to 290 s when performing radial approach. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01076764.