Variability of platelet aggregate dispersal with glycoprotein IIb-IIIa antagonists eptifibatide and abciximab
Variability of platelet aggregate dispersal with glycoprotein IIb-IIIa antagonists eptifibatide and abciximab
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DOI：
10.1111/j.1538-7836.2009.03432.x
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发表时间：
2009-06-01
影响因子：
10.4
通讯作者：
Jennings, L. K.
中科院分区：
文献类型：
--
作者：
Speich, H. E.;Earhart, A. D.;Jennings, L. K.
背景资料：糖蛋白IIb-IIIa（GPIIb-IIIa）抑制剂的使用改善了急性冠状动脉综合征（ACS）患者的结局，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、减少微栓塞和恢复血管通畅的能力有关。目的：体外评价GPIIb-IIIa拮抗剂阿昔单抗和依替巴肽促进富血小板血栓解聚的能力。研究方法：通过聚集测定法在血浆中以及通过床旁和毛细血管灌注系统在全血中测定拮抗剂诱导的解聚。通过流式细胞术定量从血小板表面解离的纤维蛋白原。结果：观察到5 μ m ADP诱导的聚集体的显着解聚后，加入任何一种药物。依替巴肽组的最大解聚程度和解聚速率显著高于阿昔单抗组。这两种拮抗剂也分散2 μ g/mL（-1）胶原诱导的聚集体，再次与eptifibatide具有更大的效果。依替巴肽，而不是阿昔单抗（高达10 μ g mL（-1）），是有效的在全血中的聚集体解离成单个血小板和分散聚集体，已老化30分钟前治疗。依替巴肽还降低了动脉血流条件下灌注模型中现有的血栓负荷。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位移，这是更大的eptifibatide，纤维蛋白原结合的竞争性抑制剂，比非竞争性抑制剂，阿昔单抗。结论：这些结果表明，药物浓度和滞留时间，沿着血栓范围和年龄，可能是促进及时再通的关键决定因素。
Background: 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. Objective: To evaluate in vitro the ability of GPIIb-IIIa antagonists, abciximab and eptifibatide, to promote the disaggregation of platelet-rich thrombus. Methods: 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. Results: Significant disaggregation of 5 mu m 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 mu g mL(-1) collagen-induced aggregates, again with eptifibatide having a greater effect. Eptifibatide, but not abciximab (up to 10 mu g 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. Conclusions: These results suggest that drug concentration and residence time, along with thrombus extent and age, may be critical determinants in promoting timely recanalization.