Abciximab, eptifibatide, and tirofiban exhibit dose-dependent potencies to dissolve platelet aggregates.
Platelet GPIIb/IIIa antagonists are not only used to prevent platelet aggregation, but also in combination with thrombolytic agents for the treatment of coronary thrombi. Recent data indicate a potential of abciximab alone to dissolve thrombi in vivo. We investigated the potential of abciximab, eptifibatide, and tirofiban to dissolve platelet aggregates in vitro. Adenosine diphosphate (ADP)-induced platelet aggregation could be reversed in a concentration-dependent manner by all three GPIIb/IIIa antagonists when added after the aggregation curve reached half-maximal aggregation. The concentrations chosen are comparable with in vivo plasma concentrations in clinical applications. Disaggregation reached a maximum degree of 72.4% using 0.5 microg/ml tirofiban, 91.5% using 3.75 microg/ml eptifibatide, and 48.4% using 50 microg/ml abciximab (P < 0.05, respectively). A potential fibrinolytic activity of the GPIIb/IIIa antagonists was ruled out by preincubation with aprotinin or by a plasma clot assay. A stable model Chinese hamster ovary (CHO) cell line expressing the activated form of GPIIb/IIIa was used to confirm the disaggregation capacity of GPIIb/IIIa antagonists found in platelets. Not only abciximab, but also eptifibatide and tirofiban have the potential to disaggregate newly formed platelet clusters in vitro. Because enzyme-dependent fibrinolysis does not appear to be involved, competitive removal of fibrinogen by the receptor antagonists is the most likely mechanism.
Moser
Martin
M
Division of Cardiology, University of Heidelberg, Heidelberg, Germany.
Bertram
Ulf
U
Peter
Karlheinz
K
Bode
Christoph
C
Ruef
Johannes
J
D000077284:Abciximab; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D016466:CHO Cells; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D000077542:Eptifibatide; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000502:physiology; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010455:Peptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; D000077466:Tirofiban; D000077542:Eptifibatide; D000077284:Abciximab