Escolar G, Cases A, Bastida E, Garrido M, López J, Revert L, Castillo R, Ordinas A
Servicio de Hemoterapia y Hemostasia, Hospital Clínic i Provincial, Barcelona, Spain.
Blood. 1990 Oct 1;76(7):1336-40.
Uremic patients have an impaired platelet function that has been related to membrane glycoprotein (GP) abnormalities. Using a perfusion system, we have studied the interaction of normal and uremic platelets with vessel subendothelium (SE) under flow conditions. Reconstituted blood containing washed platelets, purified von Willebrand factor (vWF) (1 U/mL), and normal washed red blood cells was exposed to de-endothelialized rabbit segments for 10 minutes at two different shear rates (800 and 1,600 seconds-1). In some experiments a monoclonal antibody to the GPIIb-IIIa complex (EDU3) was added to the perfusates. With normal platelets, the percentage of the vessel covered by platelets (%CS) was 23.1% +/- 3.7% at 800 seconds-1 and 30% +/- 4.3% at 1,600 seconds-1. Platelets were observed in contact or forming monolayers on vessel SE. EDU3 inhibited the spreading of normal platelets. The %CS (11.1% +/- 3.3%) was statistically decreased (P less than .01) and most of the platelets were observed in contact with the vessel surface. These data indicate that, under flow conditions, the interaction of vWF with GPIIb-IIIa can support the spreading of normal platelets in the absence of exogenous fibrinogen. Under the same experimental conditions, the interaction of uremic platelets with SE was markedly impaired at both shear rates studied (P less than .01 v normal platelets). The presence of EDU3 did not modify the interaction of uremic platelets. These results confirm the impairment of the platelet adhesion observed in uremic patients. Furthermore, they indicate the presence of a functional defect in the interaction of vWF with GPIIb-IIIa. The fact that perfusions with normal and uremic platelets in the presence of an antibody to the GPIIb-IIIa complex did not show any differences gives indirect evidence on a functionally normal interaction vWF/GPIb in uremic patients.
尿毒症患者存在血小板功能受损，这与膜糖蛋白（GP）异常有关。我们使用灌注系统，研究了正常血小板和尿毒症血小板在流动条件下与血管内皮下层（SE）的相互作用。将含有洗涤过的血小板、纯化的血管性血友病因子（vWF）（1 U/mL）和正常洗涤过的红细胞的重组血液，在两种不同的剪切速率（800和1600秒-1）下暴露于去内皮的兔血管段10分钟。在一些实验中，向灌注液中加入了针对GPIIb-IIIa复合物的单克隆抗体（EDU3）。对于正常血小板，在800秒-1时，被血小板覆盖的血管百分比（%CS）为23.1%±3.7%，在1600秒-1时为30%±4.3%。观察到血小板与血管SE接触或形成单层。EDU3抑制了正常血小板的铺展。%CS（11.1%±3.3%）在统计学上降低（P小于0.01），并且大多数血小板被观察到与血管表面接触。这些数据表明，在流动条件下，vWF与GPIIb-IIIa的相互作用可以在没有外源性纤维蛋白原的情况下支持正常血小板的铺展。在相同的实验条件下，在所研究的两种剪切速率下，尿毒症血小板与SE的相互作用均明显受损（与正常血小板相比，P小于0.01）。EDU3的存在并未改变尿毒症血小板的相互作用。这些结果证实了在尿毒症患者中观察到的血小板黏附受损。此外，它们表明vWF与GPIIb-IIIa相互作用中存在功能缺陷。在存在针对GPIIb-IIIa复合物的抗体的情况下，正常血小板和尿毒症血小板的灌注未显示任何差异，这一事实间接证明了尿毒症患者中vWF/GPIb的功能正常相互作用。
