Yamaguchi Tomoko, Amano Kagehiro, Chikasawa Yushi, Bingo Masato, Kinai Ei
Department of Laboratory Medicine, Tokyo Medical University, Tokyo, JPN.
Cureus. 2025 Jul 23;17(7):e88625. doi: 10.7759/cureus.88625. eCollection 2025 Jul.
Acquired hemophilia A (AHA) is a life-threatening bleeding disorder caused by autoantibodies against coagulation factor VIII (FVIII). While immunosuppressive therapy (IST) can eradicate these autoantibodies, it may fail or cause adverse events, especially in elderly patients. Clinical trials involving AHA patients have confirmed the efficiency of emicizumab, a bispecific antibody mimicking FVIII widely used in congenital hemophilia A with or without inhibitors, but the long-term safety and effectiveness in perioperative hemostatic management remain unclear. These issues are important due to the high risk of thrombosis in AHA patients. This report details four years of continuous use of emicizumab and perioperative management in an elderly woman in her 90s with IST-resistant/intolerant AHA. She was diagnosed with AHA one year before the initiation of emicizumab. After initially responding to steroid pulse therapy with a tentative fall in FVIII autoantibodies, she experienced recurrences and repetitive episodes of massive cutaneous bleeding within a year during corticosteroid tapering, which required continuous high-dose steroid therapy. Emicizumab was initiated via enrollment in the AGEHA clinical trial. During the four years of continuous use (the longest reported duration), no major bleeding or adverse events were recorded. The patient underwent emergency surgery for appendicitis, during which hemostasis was maintained with recombinant activated factor VII (rFVIIa). Despite minimal intraoperative blood loss, prolonged drain-site bleeding occurred, possibly due to low emicizumab levels indicated by FVIII activity measured by chromogenic assay. rFVIIa was tapered gradually to postoperative day 27 without thrombotic complications. This case highlights the utility of emicizumab in IST-resistant AHA patients by achieving effective hemostasis and safety against IST-related toxicity. It also demonstrates the beneficial effects of rFVIIa in hemostasis during surgery, emphasizing the importance of careful monitoring in balancing bleeding and thrombotic risks.
获得性血友病A(AHA)是一种由抗凝血因子VIII(FVIII)自身抗体引起的危及生命的出血性疾病。虽然免疫抑制疗法(IST)可以消除这些自身抗体,但可能会失败或引起不良事件,尤其是在老年患者中。涉及AHA患者的临床试验已证实了艾美赛珠单抗的有效性,艾美赛珠单抗是一种模拟FVIII的双特异性抗体,广泛用于有或没有抑制剂的先天性血友病A,但围手术期止血管理的长期安全性和有效性仍不清楚。由于AHA患者血栓形成风险高,这些问题很重要。本报告详细介绍了一名90多岁患有IST耐药/不耐受AHA的老年女性连续四年使用艾美赛珠单抗及围手术期管理的情况。她在开始使用艾美赛珠单抗前一年被诊断为AHA。最初对类固醇冲击疗法有反应,FVIII自身抗体暂时下降,但在皮质类固醇减量期间,她在一年内经历了复发和反复的大量皮肤出血发作,这需要持续高剂量的类固醇治疗。通过参加AGEHA临床试验开始使用艾美赛珠单抗。在连续使用的四年(报道的最长持续时间)中,未记录到重大出血或不良事件。患者因阑尾炎接受急诊手术,术中使用重组活化因子VII(rFVIIa)维持止血。尽管术中失血极少,但引流部位出血持续时间延长,可能是由于发色底物法测定的FVIII活性表明艾美赛珠单抗水平较低。rFVIIa逐渐减量至术后第27天,未出现血栓并发症。该病例突出了艾美赛珠单抗在IST耐药AHA患者中通过实现有效止血和对抗IST相关毒性的安全性的效用。它还证明了rFVIIa在手术止血中的有益作用,强调了在平衡出血和血栓形成风险时进行仔细监测的重要性。