Comprehensive Center for Bleeding Disorders, Blood Center of Wisconsin, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Haemophilia. 2011 Nov;17(6):895-905. doi: 10.1111/j.1365-2516.2011.02534.x. Epub 2011 Apr 27.
von Willebrand disease (VWD) is the most common inherited bleeding disorder. Treatment guidelines recommend the use of von Willebrand factor/factor VIII (VWF/FVIII) concentrate for VWD patients with type 2 or 3 VWD undergoing surgery, and type 1 patients undergoing surgery who are unresponsive, or for whom desmopressin acetate is contraindicated. This prospective, open-label, multinational study evaluated the safety, efficacy and optimal dosing of a VWF/FVIII concentrate (Humate-P) in subjects with VWD undergoing elective surgery. Dosing was based on VWF ristocetin cofactor (VWF:RCo) and FVIII pharmacokinetic assessments performed before surgery. Pharmacokinetic assessments were completed in 33 adults and 9 children. Haemostatic efficacy was assessed on a 4-point scale (excellent, good, moderate/poor or none). Overall effective haemostasis was achieved in 32/35 subjects. Median terminal VWF:RCo half-life was 11.7 h, and median incremental in vivo recovery was 2.4 IU dL(-1) per IU kg(-1) infused. Major haemorrhage occurred after surgery in 3/35 cases despite achieving target VWF and FVIII levels. Median VWF/FVIII concentrate loading doses ranged from 42.6 IU VWF:RCo kg(-1) (oral surgery) to 61.2 IU VWF:RCo kg(-1) (major surgery), with a median of 10 (range, 2-55) doses administered per subject. Adverse events considered possibly treatment-related (n = 6) were generally mild and of short duration. The results indicate that this VWF/FVIII concentrate is safe and effective in the prevention of excessive bleeding during and after surgery in individuals with VWD.
血管性血友病（VWD）是最常见的遗传性出血性疾病。治疗指南建议，对于接受手术的 2 型或 3 型 VWD 患者，以及对去氨加压素无反应或禁忌使用去氨加压素的 1 型 VWD 患者，使用血管性血友病因子/因子 VIII（VWF/FVIII）浓缩物进行治疗。这项前瞻性、开放标签、多国研究评估了 VWD 患者接受择期手术时使用 VWF/FVIII 浓缩物（Humate-P）的安全性、疗效和最佳剂量。剂量基于手术前进行的 VWF 瑞斯托霉素辅因子（VWF：RCo）和 FVIII 药代动力学评估。33 名成年人和 9 名儿童完成了药代动力学评估。止血效果评估采用 4 分制（优秀、良好、中等/差或无）。35 例受试者中的 32 例达到总体有效止血。终端 VWF：RCo 半衰期中位数为 11.7 小时，体内增量恢复中位数为每输注 1IU/kg 增加 2.4IU/dL(-1)。尽管达到了目标 VWF 和 FVIII 水平，但 35 例患者中有 3 例在手术后仍发生大出血。中位 VWF/FVIII 浓缩物负荷剂量范围为 42.6IU VWF：RCo/kg（口腔手术）至 61.2IU VWF：RCo/kg（大手术），中位数为每个患者输注 10（范围为 2-55）剂。认为可能与治疗相关的不良事件（n=6）通常为轻度且持续时间短。结果表明，这种 VWF/FVIII 浓缩物在预防 VWD 个体手术期间和手术后过度出血方面是安全有效的。
