Chavin S I
Am J Hematol. 1984 Apr;16(3):297-306. doi: 10.1002/ajh.2830160312.
Factor VIII (antihemophilic factor) is the protein that is deficient or defective in patients with classical hemophilia and Von Willebrand syndrome. Factor VIII in plasma is thought to be associated in a complex with the highest molecular weight multimers of another glycoprotein, Von Willebrand protein. Highly purified human factor VIII appears to have an Mr of between 200,000 and 300,000 and to consist of several polypeptide chains. The concentration of factor VIII in plasma is around 100-200 ng/ml, equivalent to around 1 nM. The purified proteins retain one or more of the known properties of factor VIII, including the acceleration of factor IXa-mediated activation of factor X, ability to be activated by thrombin and factor Xa, inactivation by activated protein C, and by human antibodies to factor VIII. Among the known clotting factors, factors VIII and V are exceptional in not possessing enzymatic activity. Factors IXa and VIII and X appear to form a functional complex, all of which need to be present and active simultaneously for optimal activation of factor X. The mechanism by which factor VIII promotes activation of factor X by factor IXa is not known, but the major effect is to increase the rate of the reaction. Following treatment of factor VIII with thrombin, a new and smaller polypeptide Mr around 70,000 +/- 5,000 is produced. Factors IXa and Xa also have been reported to activate factor VIII. It is not known whether limited proteolytic cleavage is required absolutely for the expression of factor VIII activity or if it only increases an activity already expressed by the uncleaved protein. Factor VIII is inactivated by thrombin and by activated protein C. Thus, factor VIII can be modulated by at least four of the serine proteases in the clotting system. A major goal for future research is to increase our understanding of the role in blood clotting played by factor VIII, and to apply this information to clinical problems which result from inherited abnormalities of factor VIII.
凝血因子VIII（抗血友病因子）是经典血友病和血管性血友病患者体内缺乏或有缺陷的蛋白质。血浆中的凝血因子VIII被认为与另一种糖蛋白——血管性血友病蛋白的最高分子量多聚体形成复合物。高度纯化的人凝血因子VIII的相对分子质量似乎在200,000至300,000之间，由几条多肽链组成。血浆中凝血因子VIII的浓度约为100 - 200 ng/ml，相当于约1 nM。纯化后的蛋白质保留了凝血因子VIII的一种或多种已知特性，包括加速因子IXa介导的因子X活化、被凝血酶和因子Xa激活的能力、被活化蛋白C灭活以及被人抗凝血因子VIII抗体灭活。在已知的凝血因子中，凝血因子VIII和V不具有酶活性，这一点很特殊。因子IXa、VIII和X似乎形成一种功能复合物，所有这些因子都需要同时存在并具有活性才能实现因子X的最佳活化。凝血因子VIII促进因子IXa对因子X活化的机制尚不清楚，但主要作用是加快反应速率。用凝血酶处理凝血因子VIII后，会产生一种新的、相对分子质量较小的多肽，约为70,000±5,000。也有报道称因子IXa和Xa可激活凝血因子VIII。目前尚不清楚有限的蛋白水解切割对于凝血因子VIII活性的表达是否绝对必要，或者它是否只是增加了未切割蛋白已表达的活性。凝血因子VIII可被凝血酶和活化蛋白C灭活。因此，凝血因子VIII可被凝血系统中的至少四种丝氨酸蛋白酶调节。未来研究的一个主要目标是加深我们对凝血因子VIII在血液凝固中所起作用的理解，并将这些信息应用于由凝血因子VIII遗传性异常导致的临床问题。
