Griggs T R, Webster W P, Cooper H A, Wagner R H, Brinkhous K M
Proc Natl Acad Sci U S A. 1974 May;71(5):2087-90. doi: 10.1073/pnas.71.5.2087.
Aggregation of human platelets by bovine plasma was recently recognized as a marker for the study of the antihemophilic and von Willebrand factors. A similar marker in porcine plasma is shown to be specific for the platelet-active von Willebrand factor of plasma, but not for the antihemophilic factor (factor VIII). A new quantitative assay for the von Willebrand factor is based on the dose-response relationship observed between the concentration of von Willebrand factor and platelet aggregation times determined macroscopically. Bleeder swine, homozygous for von Willebrand disease, had no detectable platelet aggregating activity, while heterozygotes, carriers of the disease, had reduced levels of approximately 50% of normal. Exact detection of non-obligate carriers, hitherto impossible, becomes readily feasible because of the gene dosage relationship to the von Willebrand factor plasma levels. Transfusion of bleeder swine with normal plasma results in an immediate post-transfusion rise of the von Willebrand factor, followed by a rapid falloff. At 24 hr post-transfusion, no von Willebrand factor is detectable at a time when the factor VIII response is at its maximum. The discordance in plasma levels of this platelet-active von Willebrand factor and factor VIII in carrier animals and in the bleeder animals after transfusion suggests a different molecular and genetic basis for these two biological activities.
牛血浆对人血小板的聚集作用最近被认为是研究抗血友病因子和血管性血友病因子的一个标志物。猪血浆中的一种类似标志物被证明对血浆中具有血小板活性的血管性血友病因子具有特异性，但对抗血友病因子（因子VIII）不具有特异性。一种新的血管性血友病因子定量测定方法基于宏观测定的血管性血友病因子浓度与血小板聚集时间之间观察到的剂量反应关系。患有血管性血友病的纯合子出血猪没有可检测到的血小板聚集活性，而作为该疾病携带者的杂合子，其水平降低至正常水平的约50%。由于血管性血友病因子血浆水平与基因剂量的关系，迄今无法实现的非必需携带者的准确检测变得很容易实现。给出血猪输注正常血浆会导致输血后血管性血友病因子立即升高，随后迅速下降。输血后24小时，当因子VIII反应达到最大值时，检测不到血管性血友病因子。载体动物和输血后出血动物中这种具有血小板活性的血管性血友病因子和因子VIII血浆水平的不一致表明这两种生物学活性具有不同的分子和遗传基础。
