title: Profound inhibition of platelet aggregation with monoclonal antibody 7E3 Fab after thrombolytic therapy. Results of the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) 8 Pilot Study.
abstract: OBJECTIVE
  This study was undertaken to establish evidence for physiologic activity and to study the safety of murine-derived monoclonal antibody 7E3 Fab (m7E3 Fab) in patients receiving recombinant tissue-type plasminogen activator (rt-PA).
  
  
  BACKGROUND
  Platelet aggregation is believed to be a significant factor in the failure of pharmacologic reperfusion. By binding to the glycoprotein IIb/IIIa receptor, m7E3 Fab inhibits platelet aggregation and has been shown experimentally to decrease the time required for lysis and to prevent reocclusion. However, the safety of profound platelet inhibition after thrombolysis for acute myocardial infarction has not been tested in humans.
  
  
  METHODS
  Sixty patients receiving rt-PA, aspirin and heparin for acute myocardial infarction received m7E3 Fab bolus injections in ascending doses at 3, 6 and 15 h after initiation of the thrombolytic infusion. Ten patients treated with rt-PA but not m7E3 Fab were studied as control subjects.
  
  
  RESULTS
  Receptor site blockade and inhibition of platelet aggregation to 20 mumol/liter adenosine diphosphate were maximal at a dose of 0.25 mg/kg body weight of m7E3 Fab. Fifteen (25%) m7E3 Fab-treated patients and five (50%) control patients had major bleeding; eight of these events in seven m7E3 Fab-treated patients and one in a control patient occurred at the time of aortocoronary bypass surgery. Recurrent ischemia occurred in eight (13%) m7E3 Fab-treated patients and two (20%) control subjects. Coronary angiography was performed in 43 patients; the infarct-related coronary artery was patent in 5 of 9 (56%) control patients and 34 (92%) of 37 patients receiving m7E3 Fab.
  
  
  CONCLUSIONS
  Profound inhibition of platelet aggregation after thrombolysis was associated with bleeding rates comparable to those in control patients and a low rate of recurrent ischemia. The combination of m7E3 Fab and rt-PA, heparin and aspirin appears to be a promising and safe combination that should be evaluated in further studies of patients with acute myocardial infarction.
authors.affiliation: Section of Cardiology, Baylor College of Medicine, Methodist Hospital, Houston, Texas 77030.
authors.forename: N S
authors.initials: NS
authors.lastname: Kleiman
authors.forename: E M
authors.initials: EM
authors.lastname: Ohman
authors.forename: R M
authors.initials: RM
authors.lastname: Califf
authors.forename: B S
authors.initials: BS
authors.lastname: George
authors.forename: D
authors.initials: D
authors.lastname: Kereiakes
authors.forename: F V
authors.initials: FV
authors.lastname: Aguirre
authors.forename: H
authors.initials: H
authors.lastname: Weisman
authors.forename: T
authors.initials: T
authors.lastname: Schaible
authors.forename: E J
authors.initials: EJ
authors.lastname: Topol
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy*; D010865:Pilot Projects; D010974:Platelet Aggregation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects / Q000276:immunology*; D012008:Recurrence; D013921:Thrombocytopenia / Q000139:chemically induced; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010980:Platelet Membrane Glycoproteins; D010959:Tissue Plasminogen Activator