Flow cytometry reveals activated GP IIb-IIIa complexes on platelets from patients undergoing thrombolytic therapy after acute myocardial infarction.
We report the detection of activated GP IIb-IIIa complexes on platelets of patients undergoing thrombolytic therapy after acute myocardial infarction. Protocols were established for the monoclonal antibodies (mAbs): VH10, anti-P-selectin, a marker of platelet secretion; 9F9 and F26, two anti-RIBS (receptor-induced binding sites) mAbs specific for fibrinogen (Fg) bound to the GP IIb-IIIa receptor. Of ten patients studied: two were treated with streptokinase, four with APSAC (anisoylated plasminogen-streptokinase activator complex), and three with rt-PA. Platelets were tested on at least five occasions in the week following therapy. The percentage of platelets positive with 9F9 was often high, and reached a maximum within three days. By this time, plasma Fg levels, which fell during fibrinolysis, had begun to return to normal. Levels of activated platelets had fallen to baseline after 7 days. PAC-1, a mAb which binds directly to the activated GP IIb-IIIa complex, confirmed the results with 9F9, but F26 was a less sensitive probe. Binding of the anti-P-selectin mAb (VH10) was low, showing that little secretion had occurred. A concentration-dependent inhibition of 9F9 binding by RGDW peptide, a competitive inhibitor for Fg on GP IIb-IIIa, confirmed that Fg (or epitope-containing degradation products) were being located by the antibody. The activation of GP IIb-IIIa occurred despite the patients receiving aspirin and heparin. Thus platelets of some fibrinolytic patients have an increased tendency for surface activation within the first 72 h after treatment, a finding which would be compatible with an increased thrombotic tendency.
Bihour
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C
Unité de Recherche Associée 1464 Centre National de la Recherche Scientifique, Institut Fédératif de Recherche Coeur-Vaisseaux-Thrombose, Hôpital Cardiologique, Pessac, France.
Durrieu-Jaïs
C
C
Besse
P
P
Nurden
P
P
Nurden
A T
AT
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D016255:Anistreplase / Q000627:therapeutic use; D000911:Antibodies, Monoclonal; D001792:Blood Platelets / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000097:blood* / Q000188:drug therapy*; D015539:Platelet Activation; D010976:Platelet Count; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013300:Streptokinase / Q000627:therapeutic use; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D010980:Platelet Membrane Glycoproteins; D011994:Recombinant Proteins; D016255:Anistreplase; D013300:Streptokinase; D010959:Tissue Plasminogen Activator