Hemophilia Center, University Hospitals Leuven, Leuven, Belgium.
Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
Haemophilia. 2023 Jul;29(4):1049-1055. doi: 10.1111/hae.14809. Epub 2023 Jun 5.
Emicizumab is approved to prevent bleeding in patients with congenital haemophilia A with or without inhibitors. However, no randomized trials addressed the efficacy of emicizumab in acquired haemophilia A (AHA).
To report the clinical and biochemical response of emicizumab in AHA.
This single-centre retrospective study included seven adults with AHA between November 2020 and May 2022. We collected patient characteristics, laboratory coagulation parameters, the use of haemostatic agents, bleeds and thrombotic events. Treatment was monitored using chromogenic FVIII assays. The assay with human reagents assesses both the emicizumab FVIII-like-activity and native patient FVIII-activity. The assay with bovine reagents only measures the patients' native FVIII-activity as emicizumab does not bind to bovine reagents.
Patients presented with spontaneous hematoma (n = 7), intramuscular bleeding (n = 2), haematuria (n = 2) and/or gastro-intestinal bleeding (n = 2). Six patients had major bleedings. At diagnosis, APTT was prolonged (91 seconds, IQR 73-103), FVIII activity was 0% (IQR 0-1) and FVIII inhibitor 182 BU/mL (IQR 104-228). Emicizumab was administered weekly (3 mg/kg) for 4 weeks, and thereafter every 2 weeks until regression of the inhibitor. Three patients received activated FVIIa (cumulative dose of 1.7 mg/kg, IQR 1.2-2.2). All bleedings were controlled after treatment initiation, without further bleeds. After starting emicizumab, FVIII-like activity reached ≥5% at 12 days (IQR 7-14), whereas recovery of the intrinsic FVIII-activity ≥5% occurred at 128 days (IQR 88-173), coinciding with the disappearance of the FVIII inhibitor. There were no safety issues.
In this AHA case series, no new clinically relevant bleeds were observed after initiation of emicizumab in conjunction with standard immunosuppressive therapy.
依库珠单抗已被批准用于预防有或无抑制剂的先天性血友病 A 患者的出血。然而，尚无随机试验评估依库珠单抗在获得性血友病 A（AHA）中的疗效。
报告依库珠单抗在 AHA 中的临床和生化反应。
这项单中心回顾性研究纳入了 2020 年 11 月至 2022 年 5 月期间的 7 例 AHA 成人患者。我们收集了患者特征、实验室凝血参数、止血剂的使用、出血和血栓事件。使用发色底物法评估治疗效果。用人试剂进行的检测同时评估依库珠单抗的 FVIII 类似物活性和患者自身的 FVIII 活性。用牛试剂进行的检测仅测量患者自身的 FVIII 活性，因为依库珠单抗不会与牛试剂结合。
患者表现为自发性血肿（n=7）、肌肉内出血（n=2）、血尿（n=2）和/或胃肠出血（n=2）。6 例患者有大出血。诊断时，APTT 延长（91 秒，IQR 73-103），FVIII 活性为 0%（IQR 0-1），FVIII 抑制剂为 182 BU/mL（IQR 104-228）。依库珠单抗每周（3mg/kg）治疗 4 周，此后每 2 周 1 次，直至抑制剂消退。3 例患者接受了活化的 FVIIa（累计剂量 1.7mg/kg，IQR 1.2-2.2）。所有出血在开始治疗后均得到控制，无进一步出血。开始使用依库珠单抗后，12 天 FVIII 类似物活性达到≥5%（IQR 7-14），而自身 FVIII 活性恢复≥5%则发生在 128 天（IQR 88-173），同时 FVIII 抑制剂消失。未出现安全性问题。
在这项 AHA 病例系列研究中，在联合标准免疫抑制治疗的基础上，依库珠单抗治疗并未导致新的有临床意义的出血。
