Abciximab treatment in vitro after aspirin treatment in vivo has additive effects on platelet aggregation, ATP release, and P-selectin expression.
To prevent arterial thrombosis, abciximab is administered together with aspirin. However, whether or not there are benefits to combine abciximab with aspirin is not yet well defined. Healthy volunteers were studied for the effect of aspirin + abciximab using sodium arachidonate and adenosine diphosphate (ADP) alone or in combination to induce platelet activation/aggregation. Abciximab produced complete inhibition of platelet aggregation induced with ADP but only 40% inhibition of aggregation induced by 0.75-mmol/l sodium arachidonate. Abciximab added in vitro to platelet-rich plasma (PRP) from platelets from aspirin-treated donors produced an almost complete inhibition of platelet aggregation. Aspirin, and abciximab alone, did not inhibit adenosine triphosphate (ATP) release as thoroughly as aspirin + abciximab did. Abciximab (3-5 microg/ml) produced inhibition of P-selectin expression induced with 5 (from 46.2 +/- 6.0% to 27.4 +/- 7.0%, P=0.002) and 20-micromol/l ADP (from 53.1 +/- 8.1% to 35.1 +/- 11.0%, P=0.019), but no effect was observed when 0.75-mmol/l sodium arachidonate was used (P=0.721). Aspirin diminished P-selectin expression in sodium arachidonate-stimulated platelets (from 77.7 +/- 11.8% to 40.2 +/- 3.6%, P<0.0001) in non-aspirinated and platelets from aspirin-treated donors, respectively. Abciximab (3, 4, and 5 microg/ml) added to platelets from aspirin-treated donors decreased P-selectin expression in platelets stimulated with sodium arachidonate from 40.2 +/- 8.6% to 25.6 +/- 11.5% (P=0.027), to 20.5 +/- 3.5% (P<0.0001), and to 22.5 +/- 1.8% (P<0.0001). We concluded that the antiplatelet effect of abciximab is greatly increased by aspirin.
Scazziota
A
A
Centro de Trombosis de Buenos Aires, Viamonte 2008, 1056, Buenos Aires, Argentina.
Altman
R
R
Rouvier
J
J
Gonzalez
C
C
Ahmed
Z
Z
Jeske
W P
WP
Walenga
J M
JM
Fareed
J
J
D000077284:Abciximab; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000096:biosynthesis; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D001241:Aspirin; D000077284:Abciximab