title: High levels of platelet inhibition with abciximab despite heightened platelet activation and aggregation during thrombolysis for acute myocardial infarction: results from TIMI (thrombolysis in myocardial infarction) 14.
abstract: BACKGROUND
  We evaluated platelet activation and aggregation in patients with acute myocardial infarction (AMI) treated with thrombolytic therapy alone or with reduced-dose thrombolysis and concomitant abciximab.
  
  
  RESULTS
  The study was performed in 20 control subjects and 51 patients with AMI before and after reperfusion with either alteplase or reteplase or reduced doses of these agents with concomitant abciximab. Platelet activation was assayed by platelet surface expression of P-selectin. Turbidometric platelet aggregation in response to ADP was measured in patients before thrombolytic therapy and 90 minutes and 24 hours after the beginning of thrombolytic therapy. P-selectin expression was greater at baseline in patients than normal control subjects (30.4% versus 9. 8%, P<0.0001) but was identical between the 2 groups after stimulation with ADP (64.4% versus 69.3%, P=0.37). However, at 24 hours, basal P-selectin expression declined in patients (P=0.0025 versus baseline), whereas ADP-stimulated P-selectin expression was lower in patients than in control subjects (48% versus 69%, P=0. 0004). When combined with reduced doses of either alteplase or reteplase, abciximab achieved 91% and 83% inhibition of 5 and 20 micromol/L ADP-induced platelet aggregation, which decreased to 46% and 40%, respectively, at 24 hours. No appreciable difference in the platelet inhibition profile of abciximab was observed between the 2 thrombolytics.
  
  
  CONCLUSIONS
  Platelet activation and aggregation are heightened in the setting of thrombolysis for AMI. Despite this enhanced level of platelet activation, abciximab, combined with a reduced-dose thrombolytic, inhibited platelet aggregation similarly to the level reported in elective settings.
authors.affiliation: Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Coulter
authors.forename: C P
authors.initials: CP
authors.lastname: Cannon
authors.forename: K A
authors.initials: KA
authors.lastname: Ault
authors.forename: E M
authors.initials: EM
authors.lastname: Antman
authors.forename: F
authors.initials: F
authors.lastname: Van de Werf
authors.forename: A A
authors.initials: AA
authors.lastname: Adgey
authors.forename: C M
authors.initials: CM
authors.lastname: Gibson
authors.forename: R P
authors.initials: RP
authors.lastname: Giugliano
authors.forename: M A
authors.initials: MA
authors.lastname: Mascelli
authors.forename: J
authors.initials: J
authors.lastname: Scherer
authors.forename: E S
authors.initials: ES
authors.lastname: Barnathan
authors.forename: E
authors.initials: E
authors.lastname: Braunwald
authors.forename: N S
authors.initials: NS
authors.lastname: Kleiman
mesh_terms: D000077284:Abciximab; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D017023:Coronary Angiography; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D019007:P-Selectin / Q000096:biosynthesis; D010960:Plasminogen Activators / Q000008:administration & dosage*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D005343:Fibrinolytic Agents; D007140:Immunoglobulin Fab Fragments; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; C087896:reteplase; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D000077284:Abciximab