title: Abciximab does not inhibit the increase of thrombin generation produced in platelet-rich plasma in vitro by sodium arachidonate or tissue factor.
abstract: Aspirin and platelet membrane glycoprotein (GP) IIb/IIIa blockers are currently used for acute coronary events, and in percutaneous coronary intervention for preventing further coronary outcomes, because they inhibit platelet function. Aspirin also inhibits thrombin generation (TG) in platelet-rich plasma (PRP) activated by sodium arachidonate (AA). The effect of the platelet membrane GP IIb-IIIa (integrin alpha(IIb)beta(3)) blocker abciximab on thrombin generation was studied in vitro using PRP. Thirty healthy volunteers taking no medication, and 28 volunteers who had taken aspirin (160 mg/day for 3-4 days), were included in the protocol. Control or in vivo aspirinated PRP, stimulated or not by AA or tissue factor (TF), was investigated for the inhibitory effect of abciximab pre-incubated for 3 minutes. AA and TF added in vitro activated non-aspirinated PRP: lag-time (LT) and time to peak (TTP) were significantly shortened. Peak TG (PTG) and endogenous thrombin potential (ETG) were increased by AA but not TF; thus, AA seems to be more efficient than TF for TG in this system. Abciximab added in vitro to non-activated, non-aspirinated PRP had no effect on LT, TTP, or ETP, but caused a decrease in PTG that was not statistically significant. Abciximab (3 or 4 microg/mL) added in vitro to AA or TF-activated, non-aspirinated PRP produced no effect on TG, although in aspirinated platelets both LT and time to peak were prolonged. AA as well as TF added in vitro to PRP or in vivo aspirinated PRP increased TG, although AA seems to be more efficient in our assay system. Abciximab, which affects non-aspirinated, nonactivated PRP weakly, has no effect on AA or TF in activated control PRP or in vivo aspirinated PRP.
authors: Centro de Trombosis de Buenos Aires, School of Medicine, University of Buenos Aires, Argentina. draltman@arnet.com.ar
authors: Raul
authors: R
authors: Altman
authors: Alejandra
authors: A
authors: Scazziota
authors: Silvina
authors: S
authors: Santoro
authors: Claudio
authors: C
authors: Gonzalez
mesh_terms: D000077284:Abciximab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D012016:Reference Values; D013917:Thrombin / Q000096:biosynthesis*; D013925:Thromboplastin / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D013925:Thromboplastin; D013917:Thrombin; D001241:Aspirin; D000077284:Abciximab