(Circulation. 2000;101:1122.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
From the Department of Bioengineering, Rice University (B.J.F., N.A.T., L.V.M.); the Department of Medicine, Baylor College of Medicine (N.S.K., N.G., K.M.), Houston, Tex; Eli Lilly & Co (M.B.E.), Indianapolis, Ind; and Centocor, Inc (M.A.M.), Malverne, Pa.
Correspondence to Larry V. McIntire, PhD, Department of Bioengineering, Rice University, PO Box 1892, Houston, TX 77251. E-mail mcintire{at}rice.edu
BackgroundAbciximab 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.
Methods and ResultsWhole 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
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-selectinmediated leukocyte adhesion on the collagen/von
Willebrand factorplatelet surface.
ConclusionsCombined 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-selectinmediated leukocyte adhesion.
Key Words: platelets leukocytes thrombosis abciximab ticlopidine angioplasty
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