Turitto V T, Weiss H J, Baumgartner H R
J Clin Invest. 1984 Nov;74(5):1730-41. doi: 10.1172/JCI111591.
Blood interaction with the subendothelium of rabbit aorta was investigated in an annular perfusion chamber using patients with von Willebrand's disease, hemophilia, and afibrinogenemia. The vessels were exposed to nonanticoagulated blood for a range of flow conditions (wall shear rates of 650-3,300 s-1) and exposure times (1.5-10 min). The resultant platelet and fibrin interaction was quantified by the use of several morphometric techniques, one of which was developed to measure more precisely the dimensions (height and volume) of platelet thrombi attached to the subendothelium. A major finding was that under flow conditions in which little or no defect in platelet adhesion was observed in von Willebrand's disease, platelet thrombus height and volume in this disorder were significantly reduced as compared with normal controls or patients with hemophilia. Thus, Factor VIII/von Willebrand factor (VIII/VWF) may mediate not only the adhesion of platelets to subendothelium but also platelet-platelet attachments necessary for normal thrombus development. The level of Factor VIII:coagulant activity (VIII: C) was also observed to influence the resultant thrombus height and volume deposited on subendothelium, presumably through the generation of thrombin or some other procoagulant factor preceding fibrin formation, since normal values of thrombus dimensions were always observed in a patient with a fibrinogen deficiency. The influence of VIII:C became greater as shear rate was reduced, whereas as shear rate was increased, VIII/VWF was more dominant in determining the resultant platelet deposition on subendothelium. Thus, the deficiencies of VIII:C and VIII/VWF in hemophilia and von Willebrand's disease can lead to various abnormalities in platelet and fibrin association with subendothelium. The importance of a particular deficiency will depend strongly on the local blood flow conditions.
在一个环形灌注室中，使用患有血管性血友病、血友病和无纤维蛋白原血症的患者，研究了兔主动脉内皮下层与血液的相互作用。在一系列流动条件（壁面剪切速率为650 - 3300 s⁻¹）和暴露时间（1.5 - 10分钟）下，将血管暴露于未抗凝的血液中。通过几种形态计量学技术对由此产生的血小板和纤维蛋白相互作用进行定量，其中一种技术是专门开发用于更精确测量附着于内皮下层的血小板血栓的尺寸（高度和体积）。一个主要发现是，在血管性血友病患者中观察到血小板黏附几乎没有缺陷的流动条件下，与正常对照组或血友病患者相比，该疾病中的血小板血栓高度和体积显著降低。因此，因子VIII/血管性血友病因子（VIII/VWF）可能不仅介导血小板与内皮下层的黏附，还介导正常血栓形成所需的血小板 - 血小板附着。还观察到因子VIII：凝血活性（VIII：C）水平会影响沉积在内皮下层的血栓高度和体积，推测是通过在纤维蛋白形成之前产生凝血酶或其他一些促凝血因子，因为在纤维蛋白原缺乏的患者中总是观察到血栓尺寸的正常值。随着剪切速率降低，VIII：C的影响变得更大，而随着剪切速率增加，VIII/VWF在决定内皮下层上最终的血小板沉积方面更占主导地位。因此，血友病和血管性血友病中VIII：C和VIII/VWF的缺乏可导致血小板和纤维蛋白与内皮下层结合的各种异常。特定缺乏的重要性将强烈取决于局部血流条件。
