Concentration-dependent effect of abciximab on platelets and neutrophils in a model of cardiopulmonary bypass.
Abciximab is a GPIIb/IIIa antagonist used in percutaneous coronary interventions to avoid platelet activation, thrombosis and inflammation. We investigated whether abciximab influenced platelet activation and platelet interaction with neutrophils and polyvinyl chloride (PVC) in a cardiopulmonary bypass (CPB) model. Isolated platelets, preincubated with and without 0.1-20 microg/mL of abciximab, were resuspended with neutrophils in plasma and recirculated by a roller pump. Platelet, but not neutrophil adhesion to PVC was inhibited by abciximab. Only high doses of abciximab reduced platelet aggregation size, but simultaneously increased platelet-neutrophil aggregation. Abciximab had no effect on platelet CD62P expression or degranulation, but platelet activation on platelet-neutrophil aggregates increased with high doses. Only low doses inhibited neutrophil degranulation. The concentration-dependent effect of abciximab on platelet-neutrophil interaction reduces its usefulness and stresses the dependency on experimental design in the evaluation of abciximab. Our study does not support the use of abciximab alone in CPB. However, incorporation of surface-coating the biomaterial with abciximab may be an interesting option.
Asberg
Ann E
AE
Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology. ann.asberg@ntnu.no
Videm
Vibeke
V
D000077284:Abciximab; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects*; D002315:Cardiopulmonary Bypass; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D066298:In Vitro Techniques; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010973:Platelet Adhesiveness / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011143:Polyvinyl Chloride
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D011143:Polyvinyl Chloride; D000077284:Abciximab