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CLINICAL RESEARCH: GLYCOPROTEIN IIB/IIIA INHIBITION IN ACUTE MI

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

Shinya Goto, MD, FACC^*,*, Noriko Tamura, BS^* and Hideyuki Ishida, PhD

^* Department of Medicine, Tokai University School of Medicine, Kanagawa, Japan
Department of Physiology, Division of Cardiology, Tokai University School of Medicine, Kanagawa, Japan

Manuscript received October 29, 2003; revised manuscript received January 16, 2004, accepted February 24, 2004.

^* Reprint requests and correspondence: Dr. Shinya Goto, Division of Cardiology, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1143, Japan.
sgoto3{at}mac.com

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 µM) 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 µm, 3 ± 2 µm, and 3 ± 1 µm, 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 µm increased to 11 ± 4 µm after subsequent perfusion of control blood (n = 8). The volume of the platelet thrombi, which was 3,352 ± 1,045 µm³ before starting the second perfusion, was reduced to 778 ± 102 µm³, 812 ± 122 µm³, and 856 ± 144 µm³ 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.

Abbreviations and Acronyms   GP = glycoprotein   NIH = National Institutes of Health   VWF = von Willebrand factor

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