ABOLITION OF INVIVO PLATELET THROMBUS FORMATION IN PRIMATES WITH MONOCLONAL-ANTIBODIES TO THE PLATELET GPIIB-IIIA RECEPTOR - CORRELATION WITH BLEEDING-TIME, PLATELET-AGGREGATION, AND BLOCKADE OF GPIIB-IIIA RECEPTORS
ABOLITION OF INVIVO PLATELET THROMBUS FORMATION IN PRIMATES WITH MONOCLONAL-ANTIBODIES TO THE PLATELET GPIIB-IIIA RECEPTOR - CORRELATION WITH BLEEDING-TIME, PLATELET-AGGREGATION, AND BLOCKADE OF GPIIB-IIIA RECEPTORS
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DOI：
10.1161/01.cir.80.6.1766
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发表时间：
1989-12-01
期刊：
影响因子：
37.8
通讯作者：
JORDAN, R
中科院分区：
文献类型：
--
作者：
COLLER, BS;FOLTS, JD;JORDAN, R
我们研究了抗血小板GPIIb/IIIa受体（7 E3和10 E5）的鼠单克隆抗体的F（ab“）2片段对猴模型体内血小板血栓形成的剂量反应效应，在该模型中，颈动脉狭窄，内膜损伤和亚聚集剂量肾上腺素的输注引起和增加血栓形成。两种抗体均以约0.2mg/kg的平均剂量消除血栓形成。在消除血栓形成的剂量下，离体血小板聚集并不总是被消除;类似地，出血时间仅适度延长（9.1 . ±. 1.4在这些剂量下。将剂量增加到高于消除血栓形成所需的剂量，一致地消除了离体血小板聚集，显著延长了出血时间（14.2 ± 0.01）。1.5分钟），以及GPIIb/IIIa受体的几乎定量阻断。我们的结论是，在一个显着的百分比的动物，在这个模型中，需要防止血管闭塞性血栓形成的GPIIb/IIIa封锁的程度是小于所需的废除血小板聚集，只有少数的功能GPIIb/IIIa受体的保存可能足以维持一个接近正常的出血时间。
We studied the dose-response effects of the F(ab'')2 fragments of murine monoclonal antibodies to the platelet GPIIb/IIIa receptor (7E3 and 10E5) on in vivo platelet thrombus formation in a well-characterized monkey model in which the carotid artery is stenosed and thrombus formation is provoked and augmented by intimal damage and the infusion of subaggregating doses of epinephrine. Both antibodies abolished thrombus formation with a mean dose of -0.2 mg/kg. Ex vivo platelet aggregation was not always abolished at doses that abolished thrombus formation; similarly, bleeding times were only moderately prolonged (9.1 .+-. 1.4 minutes) at these doses. Increasing the dose above that required to abolish thrombus formation consistently produced abolition of ex vivo platelet aggregation, marked prolongation of the bleeding time (14.2 .+-. 1.5 minutes), and nearly quantitative blockade of GPIIb/IIIa receptors. We conclude that in a significant percentage of animals, the extent of GPIIb/IIIa blockade required to prevent vasoocclusive thrombus formation in this model is less than that required for abolition of platelet aggregation, and that the preservation of only a minority of functional GPIIb/IIIa receptors might be adequate to maintain a nearly normal bleeding time.