Budde Ulrich, Metzner Hubert J, Müller Heinz-Georg
Coagulation Laboratory, Laboratory Association Prof. Arndt and Partners, Hamburg, Germany.
Semin Thromb Hemost. 2006 Sep;32(6):626-35. doi: 10.1055/s-2006-949668.
von Willebrand disease (vWD) is a bleeding disorder that results from defects in the quality or quantity of von Willebrand factor (vWF), a glycoprotein essential for normal thrombus formation. vWF circulates in plasma as multimers in sizes ranging up to 20,000 kd. The high molecular weight vWF (HMWvWF) multimers are most essential for primary hemostasis, whereas the lower molecular weight multimers are less functionally active. For many patients, the treatment of choice is factor replacement with a vWF/FVIII concentrate, preferably one with a high content of HMWvWF multimers. Given that the commercially available vWF/FVIII concentrates seem to differ substantially in their biochemical properties as well as in their clinical efficacy, we did a comparative study with 12 vWF/FVIII concentrates to investigate content and activities of FVIII and vWF, as well as the content of HMWvWF multimers. The content of HMWvWF multimers varied considerably among the 12 concentrates. The specific vWF activities, as assessed by ristocetin cofactor activity (vWF:RCo) and collagen-binding activity (vWF:CB), correlated well with the HMWvWF content of the products. Of the products tested, Haemate P/Humate-P had the highest content of HMWvWF multimers (with a multimer pattern closest to that of normal human plasma), the highest specific vWF activities, and the highest values of vWF:RCo and vWF:CB per unit of FVIII:coagulant (C). The goal of bleeding prophylaxis and treatment in type 2, severe type 1, and type 3 vWD patients is to normalize vWF activities (vWF:RCo and vWF:CB) and FVIII:C preferentially by vWF/FVIII concentrates containing the high vWF multimers and a high vWF:RCo/FVIII ratio to achieve normal primary and secondary hemostasis. Based on the present study of a comparative analysis of currently available vWF/FVIII concentrates, a classification of vWF/FVIII products is proposed.
血管性血友病（vWD）是一种出血性疾病，由血管性血友病因子（vWF）的质量或数量缺陷引起，vWF是正常血栓形成所必需的糖蛋白。vWF以多聚体形式在血浆中循环，大小范围可达20,000kd。高分子量vWF（HMWvWF）多聚体对初级止血最为重要，而低分子量多聚体的功能活性较低。对于许多患者来说，首选的治疗方法是用vWF/FVIII浓缩物进行因子替代，最好是一种含有高含量HMWvWF多聚体的浓缩物。鉴于市售的vWF/FVIII浓缩物在生化特性和临床疗效上似乎有很大差异，我们对12种vWF/FVIII浓缩物进行了一项比较研究，以调查FVIII和vWF的含量及活性，以及HMWvWF多聚体的含量。12种浓缩物中HMWvWF多聚体的含量差异很大。通过瑞斯托霉素辅因子活性（vWF:RCo）和胶原结合活性（vWF:CB）评估的特定vWF活性与产品的HMWvWF含量密切相关。在测试的产品中，海莫莱士/人抗血友病因子（Haemate P/Humate-P）的HMWvWF多聚体含量最高（多聚体模式最接近正常人血浆），特定vWF活性最高，每单位FVIII:凝血活性（C）的vWF:RCo和vWF:CB值也最高。2型、重度1型和3型vWD患者出血预防和治疗的目标是通过含有高vWF多聚体和高vWF:RCo/FVIII比值的vWF/FVIII浓缩物，优先使vWF活性（vWF:RCo和vWF:CB）和FVIII:C正常化，以实现正常的初级和次级止血。基于目前对现有vWF/FVIII浓缩物的比较分析研究，提出了vWF/FVIII产品的分类。
