Ettingshausen Carmen Escuriola, Lassila Riitta, Escolar Gines, Male Christoph, Schirner Kathrin, Heyder Lisa, Berntorp Erik
Haemophilia Centre Rhein Main (HZRM), Frankfurt/Main, Germany.
Department of Haematology, Helsinki University Hospital, Coagulation Disorders Unit, Comprehensive Cancer Centre, and Research Program Unit in System Oncology, University of Helsinki, Helsinki, Finland.
Haemophilia. 2025 Mar;31(2):247-262. doi: 10.1111/hae.15138. Epub 2025 Feb 9.
Von Willebrand disease (VWD) is an inherited bleeding disorder caused by deficient or dysfunctional von Willebrand factor (VWF). VWF replacement therapy is indicated in VWD management.
This systematic review was conducted to evaluate all available evidence of the efficacy, safety, dosing and consumption of pasteurized plasma-derived human coagulation FVIII/human VWF (pdVWF/FVIII; Haemate P/Humate-P) concentrate for on-demand (OD) treatment, surgical prophylaxis and long-term prophylaxis of patients with VWD. A systematic search was performed in MEDLINE and Cochrane Library databases to identify studies (7 June 1982-31 May 2023) reporting the use of pdVWF/FVIII in VWD according to predefined selection criteria. Pharmacovigilance data were also retrieved for the same period.
Fifteen studies were identified, 12 being observational and three interventional. Efficacy and safety assessments and treatment protocols varied across the studies which hindered direct comparisons. Haemostatic efficacy of pdVWF/FVIII was rated excellent/good for OD treatment in 95%-98% of bleeds and in 94%-100% of surgeries. In two separate studies, prophylactic efficacy was rated excellent/good in 100% of treatment cycles. Where reported, median annualized bleeding rates decreased from 3-24 prior prophylaxis to 0.5-6 during prophylaxis. Analysis of pharmacovigilance safety reports showed that pdVWF/FVIII was associated with a low rate of adverse events.
This systematic literature review and analysis of pharmacovigilance data summarize evidence of over 40 years of clinical use of pdVWF/FVIII, supporting its safety and efficacy in VWD.
血管性血友病（VWD）是一种由血管性血友病因子（VWF）缺乏或功能异常引起的遗传性出血性疾病。VWF替代疗法适用于VWD的治疗。
本系统评价旨在评估巴氏消毒的血浆源性人凝血因子VIII/人VWF（pdVWF/FVIII；Haemate P/Humate-P）浓缩物用于VWD患者按需（OD）治疗、手术预防和长期预防的疗效、安全性、剂量和使用情况的所有现有证据。在MEDLINE和Cochrane图书馆数据库中进行了系统检索，以识别根据预定义选择标准报告pdVWF/FVIII在VWD中使用的研究（1982年6月7日至2023年5月31日）。还检索了同一时期的药物警戒数据。
共识别出15项研究，其中12项为观察性研究，3项为干预性研究。各研究的疗效和安全性评估以及治疗方案各不相同，这妨碍了直接比较。pdVWF/FVIII的止血疗效在95%-98%的出血事件和94%-100%的手术中被评为优秀/良好。在两项独立研究中，预防性疗效在100%的治疗周期中被评为优秀/良好。在有报告的情况下，年化出血率中位数从预防前的3-24降至预防期间的0.5-6。对药物警戒安全报告的分析表明，pdVWF/FVIII与低不良事件发生率相关。
本系统文献综述和药物警戒数据分析总结了pdVWF/FVIII超过40年临床应用的证据，支持其在VWD中的安全性和有效性。
