Ability of anti-glycoprotein IIb/IIIa agents to dissolve platelet thrombi formed on a collagen surface under blood flow conditions

OBJECTIVES We examined the lytic effects of anti-glycoprotein (GP) IIb/IIIa agents on platelet thrombi formed on the collagen surface under blood flow conditions. BACKGROUND Anti-GP IIb/IIIa agents may influence platelet thrombi already formed. METHODS Blood samples were anticoagulated either by the specific antithrombin Argatroban (100 muM) or by unfractionated heparin (0.1 U/ml). After platelet thrombi were formed on a collagen surface following 6-min perfusion of whole blood obtained from eight adult donors containing fluorescinated platelets at a wall shear rate of 1,500 s(-1), additional blood samples from the same donors either containing or not containing anti-GP IIb/IIIa agents (abciximab, eptifibatide, or tirofiban) were perfused on these thrombi. The three-dimensional structures of the platelet thrombi were continuously observed by laser confocal microscopy equipped with a piezo-electric motor control unit and recorded. RESULTS The platelet thrombi started to dissolve after perfusion of blood containing the anti-GP IIb/IIIa agents, whereas their growth resumed after subsequent perfusion of control blood. Only a single layer of platelets having heights of 3 +/- 1 mum, 3 +/- 2 mum, and 3 +/- 1 mum, respectively, could be seen after 6-min perfusion of blood containing abciximab, eptifibatide, and tirofiban, whereas the initial height of the platelet thrombi of 8 +/- 2 mum increased to 11 +/- 4 mum after subsequent perfusion of control blood (n = 8). The volume of the platelet thrombi, which was 3,352 +/- 1,045 mum(3) before starting the second perfusion, was reduced to 778 +/- 102 mum(3), 812 +/- 122 mum(3), and 856 +/- 144 mum(3) after 6-min perfusion of blood containing abciximab, eptifibatide, and tirofiban, respectively. CONCLUSIONS We have shown in this study that anti-GP IIb/IIIa agents possess the ability to dissolve platelet thrombi. (C) 2004 by the American College of Cardiology Foundation.