Department of Clinical Haematology, Seth G.S. Medical College and KEM Hospital Parel, Mumbai, India.
Department of Haematology, Sahyadri Specialty Hospitals, Pune, India.
Haemophilia. 2022 Mar;28(2):286-291. doi: 10.1111/hae.14491. Epub 2022 Jan 10.
von Willebrand disease (VWD) is the common bleeding disorder with a clinically relevant bleeding prevalence of 1:10,000. von Willebrand disease patients lack both von Willebrand factor (VWF) and factor VIII (FVIII), which are critical for normal haemostasis. The conventional treatment for VWD includes desmopressin and replacement therapy with plasma derived FVIII with VWF concentrates or recombinant VWF. Development of alloantibodies is a rare occurrence, there is a paucity in the literature of treatment modalities in these patients. Not many reports are available in literature on the efficacy of emicizumab in VWD patients with or without alloantibodies to VWF.
To do systematic review of literature on emicizumab in VWD and report our experience of emicizumab in two patients of VWD METHODS: We used electronic search engines till May 2021 in 'Google scholar' and 'PubMed', to collect the case reports or case series on use of emicizumab for management of VWD. Two of our severe VWD patients were successfully treated with emicizumab. A systematic review was performed and the results discussed.
The electronic search revealed six case reports using emicizumab for treatment of VWD. Two were in vitro studies and four in patients with VWD type 3 disease. In vitro studies and in VWD patients on emicizumab, showed improvement in thrombin generation and fibrin formation. Among four patients, three had alloantibodies to VWD and one was negative. All these patients were treated with emicizumab for 6-12 m. After starting emicizumab, none of them had spontaneous bleeding requiring treatment. During treatment with emicizumab, one patient had trauma-associated soft tissue hematoma, which was treated with rFVIIa and another patient had bleeding following dental exfoliation treated with Humate P. We treated two of our VWD patients one with and one without inhibitors with emicizumab after failure of other therapies. Both the patients showed marked improvement and continued to remain well and free of bleeding episodes. None of the patients had any thrombosis or thrombotic microangiopathy (TMA) during treatment with emicizumab.
In conclusion, this review supports the safety and efficacy of emicizumab in type 3 VWD patients with or without alloantibodies. Further large studies are required to confirm the safety and efficacy of emicizumab in VWD.
血管性血友病（VWD）是一种常见的出血性疾病，其临床相关出血患病率为 1:10000。VWD 患者缺乏 von Willebrand 因子（VWF）和因子 VIII（FVIII），这对于正常止血至关重要。VWD 的常规治疗包括去氨加压素和用血浆衍生的 FVIII 与 VWF 浓缩物或重组 VWF 进行替代治疗。同种抗体的产生很少见，关于这些患者的治疗方式的文献也很少。关于 VWD 患者有无 VWF 同种抗体，emicizumab 的疗效在文献中报道较少。
对 emicizumab 在 VWD 中的应用进行系统综述，并报告我们在 2 例 VWD 患者中使用 emicizumab 的经验。
我们使用电子搜索引擎“Google Scholar”和“PubMed”检索 2021 年 5 月前发表的关于 emicizumab 治疗 VWD 的病例报告或病例系列。我们的 2 例严重 VWD 患者成功接受 emicizumab 治疗。进行了系统评价并讨论了结果。
电子搜索显示，有 6 项使用 emicizumab 治疗 VWD 的病例报告。其中 2 项为体外研究，4 项为 VWD 3 型患者。体外研究和接受 emicizumab 治疗的 VWD 患者的研究表明，凝血酶生成和纤维蛋白形成得到改善。在这 4 名患者中，有 3 名对 VWF 有同种抗体，1 名无同种抗体。所有这些患者均接受 emicizumab 治疗 6-12 个月。开始接受 emicizumab 治疗后，他们均未因自发性出血而需要治疗。在接受 emicizumab 治疗期间，1 名患者因软组织外伤血肿接受 rFVIIa 治疗，1 名患者因牙脱落出血接受 Humate P 治疗。我们在其他治疗失败后，用 emicizumab 治疗了我们的 2 例 VWD 患者，其中 1 例有抑制剂，1 例无抑制剂。这 2 例患者的病情均明显改善，且持续无出血事件发生。在接受 emicizumab 治疗期间，无患者发生血栓形成或血栓性微血管病（TMA）。
总之，本综述支持 emicizumab 在有或无同种抗体的 3 型 VWD 患者中的安全性和疗效。需要进一步的大型研究来证实 emicizumab 在 VWD 中的安全性和疗效。
