Speich H E, Earhart A D, Hill S N, Cholera S, Kueter T J, Smith J N, White M M, Jennings L K
Vascular Biology Center of Excellence, The University of Tennessee Health Science Center, Memphis, TN 38163, USA.
J Thromb Haemost. 2009 Jun;7(6):983-91. doi: 10.1111/j.1538-7836.2009.03432.x.
Utilization of glycoprotein IIb-IIIa (GPIIb-IIIa) inhibitors improves outcomes of patients with acute coronary syndromes (ACS), including those undergoing percutaneous coronary intervention (PCI). These results may be related to the ability of the inhibitors to destabilize coronary thrombi, reduce microembolization, and restore vessel patency.
To evaluate in vitro the ability of GPIIb-IIIa antagonists, abciximab and eptifibatide, to promote the disaggregation of platelet-rich thrombus.
Antagonist-induced disaggregation was assayed in plasma by aggregometry, as well as in whole blood by point of care and capillary perfusion systems. Fibrinogen dissociation from the platelet surface was quantified by flow cytometry.
Significant disaggregation of 5 microm ADP-induced aggregates was observed after addition of either agent. The maximum extent and rate of disaggregation were significantly higher with eptifibatide than with abciximab. Both antagonists also dispersed 2 microg mL(-1) collagen-induced aggregates, again with eptifibatide having a greater effect. Eptifibatide, but not abciximab (up to 10 microg mL(-1)), was efficient at dissociating aggregates to single platelets in whole blood and dispersing aggregates that had been aged for 30 min before treatment. Eptifibatide also reduced existing thrombus burden in the perfusion model under arterial flow conditions. A key mechanism of aggregate dispersal was antagonist-induced displacement of platelet-bound fibrinogen, which was greater with eptifibatide, a competitive inhibitor of fibrinogen binding, than with the noncompetitive inhibitor, abciximab.
These results suggest that drug concentration and residence time, along with thrombus extent and age, may be critical determinants in promoting timely recanalization.
糖蛋白IIb-IIIa（GPIIb-IIIa）抑制剂的应用可改善急性冠脉综合征（ACS）患者的预后，包括接受经皮冠状动脉介入治疗（PCI）的患者。这些结果可能与抑制剂使冠状动脉血栓不稳定、减少微栓塞及恢复血管通畅的能力有关。
在体外评估GPIIb-IIIa拮抗剂阿昔单抗和依替巴肽促进富含血小板血栓解聚的能力。
通过凝集测定法在血浆中以及通过即时检测和毛细血管灌注系统在全血中检测拮抗剂诱导的解聚。通过流式细胞术对纤维蛋白原从血小板表面的解离进行定量。
添加任一药物后均观察到5微米ADP诱导的聚集体出现显著解聚。依替巴肽的最大解聚程度和速率显著高于阿昔单抗。两种拮抗剂也能分散2微克/毫升胶原诱导的聚集体，同样依替巴肽的效果更佳。依替巴肽（而非阿昔单抗，高达10微克/毫升）能有效使全血中的聚集体解离为单个血小板，并分散治疗前已形成30分钟的聚集体。在动脉血流条件下的灌注模型中，依替巴肽也能减轻现有血栓负荷。聚集体分散的一个关键机制是拮抗剂诱导的血小板结合纤维蛋白原的置换，作为纤维蛋白原结合竞争性抑制剂的依替巴肽比非竞争性抑制剂阿昔单抗的作用更强。
这些结果表明，药物浓度和停留时间以及血栓范围和年龄可能是促进及时再通的关键决定因素。
