Mannucci P M, Tenconi P M, Castaman G, Rodeghiero F
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Policlinico Hospital, Milan, Italy.
Blood. 1992 Jun 15;79(12):3130-7.
Until recently, cryoprecipitate has been the treatment of choice in patients with severe von Willebrand disease (vWD) because it can transiently correct low plasma levels of factor VIII coagulant activity (FVIII:C) and shorten or normalize the prolonged bleeding time (BT), the two laboratory hallmarks of the disease. However, cryoprecipitate may still transmit blood-borne viruses, whereas the development of virucidal methods have rendered plasma concentrates containing FVIII:C and von Willebrand factor (vWF) safer. To establish their potential usefulness in the treatment of vWD, we compared the effect of four virus-inactivated concentrates on FVII:C and vWF plasma levels and the BT (template method) in 10 patients with severe vWD using a crossover randomized design. The concentrates were an intermediate-purity, pasteurized FVIII-vWF concentrate; an intermediate-purity, dry-heated FVIII-vWF concentrate; a solvent/detergent-treated vWF concentrate, containing little FVIII; and a high-purity solvent/detergent-treated FVIII-vWF concentrate. All concentrates were equally effective in attaining normal and sustained levels of FVIII:C postinfusion, although peak levels were more delayed after the vWF concentrate. The effect of concentrates on the BT, however, was less uniform and satisfactory. The pasteurized FVIII-vWF concentrate transiently corrected, completely or partially, the BT in 8 of 10 patients, the dry-heated and solvent/detergent FVIII/vWF concentrates in five, whereas in no patient did the vWF concentrate correct the BT according to the criteria used in this study. These effects on the BT were not related to the plasma levels of ristocetin cofactor activity-attained postinfusion (100 U/dL or more in the majority of patients) or to the multimeric structure of vWF in concentrates (defective in larger multimers in all cases). In conclusion, even though virus-inactivated concentrates can be used to increase FVIII:C levels in patients with severe vWD, none of the concentrates studied by us consistently normalizes the BT in a sustained fashion.
直到最近，冷沉淀一直是重度血管性血友病（vWD）患者的首选治疗方法，因为它可以暂时纠正血浆中凝血因子VIII促凝活性（FVIII:C）水平过低的情况，并缩短或使延长的出血时间（BT）恢复正常，这是该疾病的两个实验室特征。然而，冷沉淀仍可能传播血源性病毒，而灭病毒方法的发展使含有FVIII:C和血管性血友病因子（vWF）的血浆浓缩物更安全。为了确定它们在治疗vWD中的潜在效用，我们采用交叉随机设计，比较了四种病毒灭活浓缩物对10例重度vWD患者的FVII:C和vWF血浆水平以及BT（模板法）的影响。这些浓缩物分别是一种中间纯度的巴氏消毒FVIII-vWF浓缩物；一种中间纯度的干热FVIII-vWF浓缩物；一种经溶剂/去污剂处理的vWF浓缩物，含少量FVIII；以及一种高纯度溶剂/去污剂处理的FVIII-vWF浓缩物。所有浓缩物在输注后使FVIII:C达到正常和持续水平方面同样有效，尽管vWF浓缩物输注后的峰值水平延迟更久。然而，浓缩物对BT的影响不太一致且不太理想。巴氏消毒的FVIII-vWF浓缩物在10例患者中的8例中暂时完全或部分纠正了BT，干热和溶剂/去污剂FVIII/vWF浓缩物在5例患者中起到了同样作用，而根据本研究使用的标准，vWF浓缩物在任何患者中都未能纠正BT。这些对BT的影响与输注后达到的瑞斯托霉素辅因子活性血浆水平（大多数患者中为100 U/dL或更高）或浓缩物中vWF的多聚体结构无关（所有情况下较大的多聚体均有缺陷）。总之，尽管病毒灭活浓缩物可用于提高重度vWD患者的FVIII:C水平，但我们研究的所有浓缩物均不能持续使BT持续恢复正常。
