Paradoxical platelet activation was not observed on dissociation of abciximab from GpIIb-IIIa complexes.
The ability of abciximab to bind and dissociate from platelets raises the question of the conformational state of GPIIb-IIIa complexes losing abciximab and the risk of paradoxical drug-induced platelet activation. Platelets incubated with abciximab and mixed in vitro with c7E3 Fab-free platelets lost the drug to the new platelets giving a single platelet population with a unimodal abciximab distribution within 17 h. Prelabeling the receiving platelets with phycoerythrin-labeled anti-GPIb monoclonal antibody (MoAb), permitted their identification by flow cytometry. Binding of PAC-1 and AP6, two MoAbs specific for activated GPIIb-IIIa, was then assessed to both losing and receiving platelet populations during transfer of abciximab. The subpopulation losing c7E3 Fab failed to show increased binding of these MoAbs. However, PAC-1 binding increased in both subpopulations after addition of ADP. Thus GPIIb-IIIa complexes are not in an activated state after dissociation of abciximab unless there is an additional source of activation.
Ndoko
Serge
S
UMR 5533 CNRS, Hĵpital Cardiologique, Pessac, France.
Poujol
Christel
C
Combrié
Robert
R
Nurden
Alan
A
Nurden
Paquita
P
D000077284:Abciximab; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000918:Antibody Specificity; D015415:Biomarkers; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D011485:Protein Binding; D011487:Protein Conformation / Q000187:drug effects
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D007140:Immunoglobulin Fab Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000077284:Abciximab