title: Potential mechanism of acute stent thrombosis with bivalirudin following percutaneous coronary intervention in acute coronary syndromes.
abstract: BACKGROUND
  Clinical trials have demonstrated an excess of acute stent thrombosis (AST) in acute coronary syndromes patients (ACS) undergoing percutaneous coronary intervention (PCI) with bivalirudin compared to heparin. We aimed to investigate the potential mechanisms responsible for thrombus formation under bivalirudin.
  
  
  METHODS
  We compared heparin and bivalirudin during PCI for ACS in a prospective monocentre randomized study. Twenty patients were included after coronary angiography and received a loading dose (LD) of 180mg of ticagrelor at the time of PCI. They were randomly assigned to heparin (70UI/kg) intra-venous (IV) bolus or bivalirudin IV bolus of 0.75mg/kg followed by an infusion of 1.75mg/kg/h until the end of the PCI. The VASP index and thrombin generation test were used to assess the course of platelet reactivity (PR) and thrombin generation.
  
  
  RESULTS
  Thrombin generation and PR were identical in both groups at baseline. There was no difference in the course of PR following the LD over time. An optimal PR inhibition was reached 4h after the LD of ticagrelor. Heparin and bivalirudin infusion effectively inhibited thrombin generation during PCI. However, 4h after the end of bivalirudin infusion, thrombin generation had returned to its baseline value whereas in the heparin group it remained significantly inhibited compared to baseline and to the bivalirudin group 4h after the end of the infusion (p<0.01 and p<0.02 respectively).
  
  
  CONCLUSIONS
  The present study suggests that the short half-life of bivalirudin and the quick restoration of thrombin activity at a time when optimal PR is not reached may be responsible for acute stent thrombosis. Clinicaltrial.gov: NCT02428725.
authors.affiliation: Service de cardiologie, Centre hospitalo-universitaire, Aix-Marseille université, Assistance-Publique Hôpitaux de Marseille, Marseille, France; MARS cardio, Mediterranean Association for Research and Studies in Cardiology, Hôpital Nord, Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Laine
authors.affiliation: Aix-Marseille Université, INSERM UMR-S 1076, Vascular Research Center of Marseille, Marseille, France; Service d'hématologie Biologique, Centre hospitalo-universitaire Timone, Assistance-Publique Hôpitaux de Marseille, Marseille, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Frere
authors.affiliation: Département de cardiologie, Centre hospitalo-universitaire Timone, Assistance-Publique Hôpitaux de Marseille, Marseille, France; Aix-Marseille Université, INSERM UMR1062, INRA UMR1260, Nutrition, Obesity and Risk of Thrombosis, Marseille, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Cuisset
authors.affiliation: Service de cardiologie, Centre hospitalo-universitaire, Aix-Marseille université, Assistance-Publique Hôpitaux de Marseille, Marseille, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Paganelli
authors.affiliation: Service d'hématologie Biologique, Centre hospitalo-universitaire Timone, Assistance-Publique Hôpitaux de Marseille, Marseille, France; Aix-Marseille Université, INSERM UMR1062, INRA UMR1260, Nutrition, Obesity and Risk of Thrombosis, Marseille, France.
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Morange
authors.affiliation: Aix-Marseille Université, INSERM UMR-S 1076, Vascular Research Center of Marseille, Marseille, France; Service d'hématologie Biologique, Centre hospitalo-universitaire Timone, Assistance-Publique Hôpitaux de Marseille, Marseille, France.
authors.forename: Francoise
authors.initials: F
authors.lastname: Dignat-George
authors.affiliation: Aix-Marseille Université, Department of Biostatistics, Marseille, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Berbis
authors.affiliation: Service d'hématologie Biologique, Centre hospitalo-universitaire Timone, Assistance-Publique Hôpitaux de Marseille, Marseille, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Camoin-Jau
authors.affiliation: Service de cardiologie, Centre hospitalo-universitaire, Aix-Marseille université, Assistance-Publique Hôpitaux de Marseille, Marseille, France; MARS cardio, Mediterranean Association for Research and Studies in Cardiology, Hôpital Nord, Marseille, France; Service d'hématologie Biologique, Centre hospitalo-universitaire Timone, Assistance-Publique Hôpitaux de Marseille, Marseille, France. Electronic address: laurentbonello@yahoo.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bonello
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000000981:diagnostic imaging / Q000628:therapy*; D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000991:Antithrombins / Q000008:administration & dosage; D054855:Drug-Eluting Stents / Q000009:adverse effects* / Q000639:trends; D005260:Female; D005500:Follow-Up Studies; D006493:Heparin / Q000008:administration & dosage; D006629:Hirudins / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage*; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects* / Q000639:trends; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage; D013927:Thrombosis / Q000097:blood* / Q000000981:diagnostic imaging / Q000209:etiology
chemical_list: D000991:Antithrombins; D006629:Hirudins; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D006493:Heparin; C074619:bivalirudin
keywords: Acute myocardial infarction; Platelet aggregation; Stent thrombosis; Thrombin