Haemophilia Centre, Aziza Othmana Hospital, University Tunis El Manar, Tunis, Tunisia.
Department of Oncology, Paediatric Haematology, Clinical Transplantology and Paediatrics of Warsaw Medical University, Warsaw, Poland.
Blood Transfus. 2023 Jan;21(1):83-92. doi: 10.2450/2022.0329-21. Epub 2022 Apr 19.
Plasma-derived von Willebrand factor (VWF) (Wilfactin, LFB, France) was developed for prophylaxis and treatment of haemorrhages in both adults and adolescents with von Willebrand disease (VWD). Replacement therapy in paediatric patients is a key element of the clinical trial programme.
Patients aged <6 years with severe VWD were enrolled in a multinational, open-label study to evaluate the in vivo recovery for Wilfactin, and its efficacy in preventing and treating bleeding episodes and during surgery. Overall haemostatic efficacy based on a 4-point scale was assessed by investigators. The treatment period ≥18 months investigated the long-term safety.
Nine patients, including 7 with type 3 VWD were exposed to treatment with Wilfactin for up to 4.2 years. Recovery of VWF in 7 patients (n=5 type 3, n=1 type 2, n=1 type 1) was 1.8±0.4 IU/dL per IU/kg. Of the 62 bleeds, 89% were controlled with one (73%) or two (16%) infusions of Wilfactin. The median dose per infusion was 54 IU/kg. A factor VIII dose was co-administered in 1.6% of bleeds. "Excellent"/"Good" haemostatic efficacy was achieved in 90.3% of episodes. Six patients underwent 11 minor surgical interventions. Treatment duration was 1 day (range: 1-6 days) with a dose administered 30-60 minutes before procedure of 56 IU/kg (range: 41-106 IU/kg). Haemostasis was rated as "Excellent" in all surgeries. During 4-year prophylactic treatment in one patient, breakthrough bleeds were reported in 2.2% of infusions. No VWF inhibitors, thromboembolic events or allergic/anaphylactic-type reactions were observed following a total exposure of 770 days.
The results show that Wilfactin provides a safe and effective treatment in patients <6 years of age with severe VWD.
血浆衍生的 von Willebrand 因子（VWF）（Wilfactin，LFB，法国）是为预防和治疗成人和青少年 von Willebrand 病（VWD）的出血而开发的。儿科患者的替代治疗是临床试验计划的关键要素。
年龄<6 岁的严重 VWD 患者参加了一项多中心、开放性研究，以评估 Wilfactin 的体内恢复情况及其预防和治疗出血发作以及手术期间的疗效。研究者根据 4 分制评估总体止血疗效。治疗期≥18 个月可考察长期安全性。
9 名患者（包括 7 名 3 型 VWD 患者）接受了长达 4.2 年的 Wilfactin 治疗。7 名患者（5 名 3 型，1 名 2 型，1 名 1 型）的 VWF 恢复率为 1.8±0.4 IU/dL/每 IU/kg。62 次出血中，89%用一次（73%）或两次（16%）Wilfactin 输注控制。每次输注的中位数剂量为 54 IU/kg。1.6%的出血中联合使用了因子 VIII 剂量。90.3%的出血事件达到“优秀”/“良好”止血疗效。6 名患者进行了 11 次小手术干预。治疗持续时间为 1 天（范围：1-6 天），在手术前 30-60 分钟给予 56 IU/kg（范围：41-106 IU/kg）的剂量。所有手术的止血效果均评为“优秀”。在一名患者为期 4 年的预防性治疗中，报告有 2.2%的输注发生突破性出血。在总共 770 天的暴露后，未观察到 VWF 抑制剂、血栓栓塞事件或过敏/过敏样反应。
结果表明，Wilfactin 为严重 VWD 的<6 岁患者提供了安全有效的治疗。
