Effects of abciximab, ticlopidine, and combined Abciximab/Ticlopidine therapy on platelet and leukocyte function in patients undergoing coronary angioplasty.
BACKGROUND
Abciximab and ticlopidine reduce adverse cardiovascular events after percutaneous transluminal coronary angioplasty (PTCA). The goal of the current study was to determine if combined abciximab/ticlopidine therapy inhibits arterial thrombosis more effectively than either treatment alone. The effect of each therapy on platelet-leukocyte interactions was also investigated.


RESULTS
Whole blood samples from 14 patients undergoing PTCA who received abciximab therapy, ticlopidine therapy, or both treatments were evaluated using dynamic experimental systems. Mural thrombus formation under arterial shear conditions (1500 s(-1)) was determined in a parallel plate flow chamber. Shear-induced platelet aggregation was evaluated using a cone-and-plate viscometer at a shear rate of 3000 s(-1). Of the 3 treatments, combined abciximab/ticlopidine therapy produced the most consistent reduction in shear-induced platelet aggregation and the most prolonged inhibition of mural thrombosis. Three days after PTCA, abciximab/ticlopidine treatment decreased mural thrombus formation to approximately 50% of baseline values. Abciximab treatment alone inhibited mural thrombosis for only 1 day after PTCA, whereas ticlopidine treatment alone had no significant effect. Two hours after PTCA, abciximab therapy significantly decreased the number of circulating platelet-neutrophil aggregates but significantly enhanced P-selectin-mediated leukocyte adhesion on the collagen/von Willebrand factor-platelet surface.


CONCLUSIONS
Combined therapy with abciximab and ticlopidine has a prolonged inhibitory effect on mural thrombosis formation relative to either treatment alone. Further, we demonstrated an unexpected effect of abciximab in enhancing P-selectin-mediated leukocyte adhesion.
Fredrickson
B J
BJ
Department of Bioengineering, Rice University, Houston, TX 77251, USA.
Turner
N A
NA
Kleiman
N S
NS
Graziadei
N
N
Maresh
K
K
Mascelli
M A
MA
Effron
M B
MB
McIntire
L V
LV
D000077284:Abciximab; D015906:Angioplasty, Balloon, Coronary; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D004359:Drug Therapy, Combination; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology; D019007:P-Selectin / Q000502:physiology; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control*; D013988:Ticlopidine / Q000494:pharmacology / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D007140:Immunoglobulin Fab Fragments; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D013988:Ticlopidine; D000077284:Abciximab