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治疗制剂中凝血因子 VIII 和血管性血友病因子的超速离心分析

Ultracentrifugal analysis of factor VIII and von Willebrand factor in therapeutic preparations.

作者信息

Aronson D L, Chang P

机构信息

Hemostasis Laboratory, George Washington University Medical School, Washington, D.C., USA.

出版信息

Vox Sang. 1995;69(1):8-13. doi: 10.1111/j.1423-0410.1995.tb00340.x.

DOI:10.1111/j.1423-0410.1995.tb00340.x
PMID:7483501
Abstract

Plasma and therapeutic preparations of factor VIII (1 recombinant factor VIII and two monoclonally purified plasma-derived factor VIII preparations, Kogenate, and AHF-M and Monoclate, respectively) were centrifuged in a sucrose density gradient, and the fractions were analyzed for factor VIII and von Willebrand factor (vWF). The residual vWF in the monoclonally purified factor VIII preparations sediments more slowly than the vWF of plasma. In the absence of added vWF, the factor VIII in all preparations sediments more slowly than plasma factor VIII. These same preparations of factor VIII added to hemophilic plasma as a source of vWF sediment differently. The addition of either recombinant factor VIII or AHF-M results in sedimentation of the factor VIII with the plasma vFW and in a position indistinguishable from factor VIII in plasma. In contrast, when Monoclate is added to hemophilic plasma in vitro, the factor VIII sediments more slowly than the vWF of the hemophilic plasma. However, 5 min after the infusion of Monoclate into a patient with hemophilia A, the factor VIII sediments with the plasma vWF. These results indicate that the addition of recombinant factor VIII and AHF-M results in random binding to all vWF multimers of plasma, while there is little exchange between the added factor VIII in Monoclate and the plasma vWF in vitro. In contrast, when the Monoclate is infused, there is rapid binding of factor VIII to the plasma vWF.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

将血浆以及因子VIII的治疗制剂(1种重组因子VIII和2种单克隆纯化的血浆源性因子VIII制剂,分别为科跃奇和AHF-M以及莫诺凝)在蔗糖密度梯度中进行离心,然后对各组分进行因子VIII和血管性血友病因子(vWF)分析。单克隆纯化的因子VIII制剂中的残留vWF沉降速度比血浆中的vWF慢。在未添加vWF的情况下,所有制剂中的因子VIII沉降速度都比血浆因子VIII慢。将这些相同的因子VIII制剂作为vWF来源添加到血友病血浆中时沉降情况不同。添加重组因子VIII或AHF-M会导致因子VIII与血浆vWF一起沉降,且沉降位置与血浆中的因子VIII无法区分。相比之下,当在体外将莫诺凝添加到血友病血浆中时,因子VIII的沉降速度比血友病血浆中的vWF慢。然而,将莫诺凝输注到甲型血友病患者体内5分钟后,因子VIII与血浆vWF一起沉降。这些结果表明,添加重组因子VIII和AHF-M会导致其随机结合到血浆的所有vWF多聚体上,而在体外,莫诺凝中添加的因子VIII与血浆vWF之间几乎没有交换。相比之下,当输注莫诺凝时,因子VIII会迅速与血浆vWF结合。(摘要截短于250词)

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