Goto S, Sakai H, Goto M, Ono M, Ikeda Y, Handa S, Ruggeri Z M
Division of Cardiology, Department of Medicine, Tokai University School of Medicine, Kanagawa, Japan.
Circulation. 1999 Feb 9;99(5):608-13. doi: 10.1161/01.cir.99.5.608.
Experiments under controlled flow conditions indicate that the binding of von Willebrand factor (vWF) to platelet glycoprotein (GP) Ibalpha and integrin alphaIIbbeta3 (GP IIb/IIIa complex) is crucial for aggregation at elevated shear rates. We have tested how the plasma of patients with acute myocardial infarction affects this process.
Citrated plasma was obtained from 18 patients with acute myocardial infarction within 6 hours from the onset of symptoms and from 26 control subjects with chest pain syndrome without evidence of ischemia. Aggregation of normal platelets at high shear rates was significantly greater in the presence of patient than control plasma and was inhibited by both anti-GP Ibalpha and anti-alphaIIbbeta3 monoclonal antibodies. The observed values (mean+/-SD) were 47.6+/-17.8% versus 30.1+/-9.9% at 10 800 s-1 (P<0.01) and 32.9+/-14.1% versus 17.5+/-9.5% at 7200 s-1 (P<0.01), respectively, and were positively correlated with plasma vWF antigen levels and ristocetin cofactor activities. In contrast, at the lower shear rate of 1200 s-1, aggregation was similar in the presence of control or patient plasma and was not inhibited by the anti-GP Ibalpha antibody. Both vWF antigen and platelet aggregation decreased 2 weeks after the onset of myocardial infarction.
Shear-induced platelet aggregation is enhanced in plasma in the presence of acute myocardial infarction, apparently as a result of increased vWF concentration. This may contribute to the onset of acute coronary artery thrombosis and early reocclusion after reperfusion treatment.
在可控血流条件下进行的实验表明，血管性血友病因子（vWF）与血小板糖蛋白（GP）Ibalpha和整合素αIIbbeta3（GP IIb/IIIa复合物）的结合对于高剪切率下的聚集至关重要。我们测试了急性心肌梗死患者的血浆如何影响这一过程。
在症状发作后6小时内从18例急性心肌梗死患者以及26例无缺血证据的胸痛综合征对照受试者中获取枸橼酸盐血浆。在高剪切率下，正常血小板在患者血浆存在时的聚集明显大于对照血浆，并且受到抗GP Ibalpha和抗αIIbbeta3单克隆抗体的抑制。在10800 s-1时，观察值（均值±标准差）分别为47.6±17.8%和30.1±9.9%（P<0.01），在7200 s-1时分别为32.9±14.1%和17.5±9.5%（P<0.01），并且与血浆vWF抗原水平和瑞斯托霉素辅因子活性呈正相关。相比之下，在1200 s-1的较低剪切率下，对照或患者血浆存在时的聚集相似，并且不受抗GP Ibalpha抗体的抑制。心肌梗死后2周，vWF抗原和血小板聚集均降低。
在急性心肌梗死存在时，血浆中剪切诱导的血小板聚集增强，显然是由于vWF浓度增加所致。这可能有助于急性冠状动脉血栓形成的发生以及再灌注治疗后的早期再闭塞。
