Brinkhous K M
Wien Klin Wochenschr. 1982 Oct 15;94(19):509-14.
A brief review of the current status of treatment of two severe bleeder diseases, hemophilia A and von Willebrand's disease, with factor VIII concentrate is given. The functional activities deficient in the two diseases, antihemophilic factor (AHF) or coagulant factor VIII (F. VIII:C) in hemophilia, and the von Willebrand factor(s) (vWF; F.VIII R: Ag) in von Willebrand's disease, are present in a very large protein moiety of plasma, the macromolecular factor VIII complex. The rationale for replacement therapy of hemophilia depends on assessment of the severity of a given hemorrhagic episode followed by single, multiple, or continuous infusions of factor VIII concentrates sufficient to raise the plasma AHF to the hemostatic level (15 - less than 50%, depending on the severity of hemorrhage). Prophylactic regimens prevent hemorrhage but are expensive. Despite many problems in their use, the success of factor VIII concentrates in controlling severe hemorrhage and in preventing crippling by arthropathies is evident in many ways including the demand for concentrates, which now exceed the economic value of two other main products of plasma fractionation, albumin and gamma globulin. The rationale for therapy of von Willebrand's disease is dependent on the formation of the hemostatic platelet plug, which includes adhesion of platelets to a vascular site of bleeding, followed by platelet aggregation to give the hemostatic thrombus. The very large molecular weight arrays of the factor VIII complex contained in cryoprecipitate appear needed for development of the hemostatic plug. A new test for determining the plasma platelet-aggregating vWF, the Botrocetin test, appears superior to the ristocetin test. An activator factor in Bothrops snake venom is used. Some prospects for improving the factor VIII therapeutic preparations through recombinant DNA technology and through altering procedures for fractionation are outlined.
本文简要回顾了用凝血因子 VIII 浓缩剂治疗两种严重出血性疾病——甲型血友病和血管性血友病的现状。这两种疾病所缺乏的功能活性物质，即血友病中的抗血友病因子（AHF）或凝血因子 VIII（F.VIII:C），以及血管性血友病中的血管性血友病因子（vWF；F.VIII R:Ag），都存在于血浆中一个非常大的蛋白质部分，即大分子凝血因子 VIII 复合物中。血友病替代疗法的基本原理取决于对特定出血发作严重程度的评估，然后单次、多次或持续输注足够量的凝血因子 VIII 浓缩剂，以使血浆 AHF 升高到止血水平（15% - 低于 50%，取决于出血的严重程度）。预防性治疗方案可预防出血，但费用昂贵。尽管在使用凝血因子 VIII 浓缩剂时有许多问题，但它在控制严重出血和预防关节病致残方面的成功在许多方面都很明显，包括对浓缩剂的需求，目前浓缩剂的经济价值已超过血浆分馏的其他两种主要产品白蛋白和丙种球蛋白。血管性血友病治疗的基本原理取决于止血性血小板栓的形成，这包括血小板黏附于血管出血部位，随后血小板聚集形成止血血栓。冷沉淀中所含的凝血因子 VIII 复合物的非常大的分子量阵列似乎是形成止血栓所必需的。一种用于测定血浆血小板聚集性 vWF 的新试验——巴曲酶试验，似乎优于瑞斯托霉素试验。使用了矛头蝮蛇毒中的一种激活因子。本文还概述了通过重组 DNA 技术和改变分馏程序来改进凝血因子 VIII 治疗制剂的一些前景。
