Casonato A, Pontara E, Bertomoro A, Zucchetto S, Zerbinati P, Girolami A
Institute of Medical Semiotics, Second Chair of Internal Medicine, University of Padua Medical School, Padova, Italia.
J Lab Clin Med. 1997 Feb;129(2):251-9. doi: 10.1016/s0022-2143(97)90147-5.
It is well established that the large von Willebrand factor (vWf) multimers bind with high affinity to the extracellular matrix. To explore the different roles of intermediate and large vWf multimers, we studied the collagen-binding activity (vWf:CBA) of 2A vWf under nonflowing conditions in relation to the multimer organization of the molecule. Regardless of the anticoagulant used for blood collection, vWf:CBA was significantly decreased, in 4 patients with 2A von Willebrand's disease (vWd), in accordance with the lack of high and intermediate vWf multimers. After 1-deamino-8-D-arginine vasopressin (DDAVP) infusion, the appearance of circulating large and unusually large vWf multimers, in samples collected in the presence of protease inhibitors, induced a complete normalization of vWf:CBA. The peak was observed 15 minutes after DDAVP, when large and unusually large multimers were maximally represented. These effects were transient because vWf:CBA decreased after 60 minutes, even though values were still significantly higher than pre-DDAVP figures; at the same time, large vWf multimers appeared to be decreased. In contrast, samples anticoagulated with sodium citrate after DDAVP did not show a normalized vWf multimer pattern and were characterized by a persistently decreased vWf:CBA. Moreover, in all of the patients studied, platelet vWf presented normal vWf:CBA values in accordance with the normal levels and multimer organization of the vWf molecule. Our findings indicate that the collagen-binding defect displayed in vitro by type 2A vWf depends only on the lack of circulating large vWf multimers. Moreover, the observation of normal platelet vWf:CBA seems to indicate a primary role of plasma rather than platelet vWf in assuring platelet plug formation.
众所周知，大的血管性血友病因子（vWf）多聚体与细胞外基质具有高亲和力结合。为了探究中等大小和大的vWf多聚体的不同作用，我们在非流动条件下研究了2A vWf的胶原结合活性（vWf:CBA）与该分子多聚体结构的关系。无论用于采血的抗凝剂是什么，4例2A血管性血友病（vWd）患者的vWf:CBA均显著降低，这与缺乏高和中等大小的vWf多聚体一致。输注1-去氨基-8-D-精氨酸血管加压素（DDAVP）后，在存在蛋白酶抑制剂的情况下采集的样本中循环的大的和异常大的vWf多聚体的出现，使vWf:CBA完全恢复正常。在DDAVP后15分钟观察到峰值，此时大的和异常大的多聚体含量最高。这些作用是短暂的，因为60分钟后vWf:CBA下降，尽管其值仍显著高于DDAVP前的数值；与此同时，大的vWf多聚体似乎减少。相比之下，DDAVP后用柠檬酸钠抗凝的样本未显示vWf多聚体模式正常化，其特征是vWf:CBA持续降低。此外，在所有研究的患者中，血小板vWf的vWf:CBA值正常，这与vWf分子的正常水平和多聚体结构一致。我们的研究结果表明，2A vWf在体外表现出的胶原结合缺陷仅取决于循环中大的vWf多聚体的缺乏。此外，血小板vWf:CBA正常的观察结果似乎表明，在确保血小板栓形成方面，血浆而非血小板vWf起主要作用。
