抗糖蛋白IIb/IIIa药物在血流条件下溶解在胶原蛋白表面形成的血小板血栓的能力。

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

作者信息

Goto Shinya, Tamura Noriko, Ishida Hideyuki

机构信息

Department of Medicine, Tokai University School of Medicine, Kanagawa, Japan.

出版信息

J Am Coll Cardiol. 2004 Jul 21;44(2):316-23. doi: 10.1016/j.jacc.2004.02.059.

DOI:10.1016/j.jacc.2004.02.059

PMID:15261925

Abstract

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

摘要

目的

我们研究了抗糖蛋白（GP）IIb/IIIa药物在血流条件下对在胶原蛋白表面形成的血小板血栓的溶解作用。

背景

抗GP IIb/IIIa药物可能会影响已经形成的血小板血栓。

方法

血液样本用特异性抗凝血酶阿加曲班（100微摩尔）或普通肝素（0.1单位/毫升）进行抗凝。在含有荧光标记血小板的来自8名成年供体的全血以1500秒^(-1)的壁剪切率灌注6分钟后，在胶原蛋白表面形成血小板血栓，然后将来自相同供体的额外血液样本（含有或不含有抗GP IIb/IIIa药物（阿昔单抗、依替巴肽或替罗非班））灌注到这些血栓上。配备压电电机控制单元的激光共聚焦显微镜连续观察血小板血栓的三维结构并记录。

结果

灌注含有抗GP IIb/IIIa药物的血液后，血小板血栓开始溶解，而在随后灌注对照血液后其生长恢复。在灌注含有阿昔单抗、依替巴肽和替罗非班的血液6分钟后，分别只能看到单层高度为3±1微米、3±2微米和3±1微米的血小板，而血小板血栓的初始高度8±2微米在随后灌注对照血液后增加到11±4微米（n = 8）。在第二次灌注开始前血小板血栓的体积为3352±1045立方微米，在灌注含有阿昔单抗、依替巴肽和替罗非班的血液6分钟后，分别减少到778±102立方微米、812±122立方微米和856±144立方微米。