Sidonio Robert F, Young Guy, Escuriola Ettingshausen Carmen, Mahlangu Johnny, Ozelo Margareth C, Srivastava Alok, Windyga Jerzy, Lee Hye-Youn, Lelli Aurelia, Pipe Steven W
Hemophilia of Georgia Center for Bleeding and Clotting Disorders of CHOA, Atlanta, Georgia, USA.
Cancer and Blood Disorders Institute, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, California, USA.
Res Pract Thromb Haemost. 2025 Jun 17;9(4):102926. doi: 10.1016/j.rpth.2025.102926. eCollection 2025 May.
Nonfactor therapies (NFTs) such as emicizumab are increasingly becoming established for bleed prophylaxis in people with hemophilia A. Both classes of bypassing agents (BPAs; activated prothrombin complex concentrate [aPCC] and recombinant activated factor [F]VII [rFVIIa]) are required for effective bleed management in people with inhibitors receiving NFT prophylaxis, owing to the variable hemostatic responses to aPCC and rFVIIa seen in different patients. Early reports of rare thrombotic events in clinical trials of emicizumab led to the development of guidelines preferring the use of rFVIIa over aPCC for the management of breakthrough bleeding and major surgery in patients receiving emicizumab. Since these guidelines were issued, data from clinical and real-world studies have emerged that support the efficacy and safety of aPCC in this setting. In this narrative review, we aimed to evaluate the evidence on bleed management with aPCC in people with hemophilia A with inhibitors receiving emicizumab prophylaxis, as well as other NFTs. These emerging data indicate that aPCC used at doses of ≤ 100 U/kg/day in people with inhibitors receiving emicizumab is not associated with thrombotic microangiopathy or thrombotic events. As more NFTs become available for bleed prophylaxis, both classes of BPAs will be needed for bleed management in people with inhibitors. Thus, optimal use of BPAs is critical and will require an understanding of the factors that influence BPA selection, such as bleed type and location, clinical response, dosing and duration of use, accessibility and availability, and patient or caregiver preference.
诸如艾美赛珠单抗之类的非凝血因子疗法（NFTs）在预防甲型血友病患者出血方面越来越得到认可。对于接受NFT预防且产生抑制物的患者，两类旁路制剂（BPAs；活化凝血酶原复合物浓缩物[aPCC]和重组活化因子[F]VII[rFVIIa]）都是有效止血管理所必需的，这是因为在不同患者中观察到对aPCC和rFVIIa的止血反应存在差异。艾美赛珠单抗临床试验中罕见血栓事件的早期报告导致了相关指南的制定，该指南更倾向于使用rFVIIa而非aPCC来处理接受艾美赛珠单抗治疗患者的突破性出血和大手术。自这些指南发布以来，临床和真实世界研究的数据表明aPCC在这种情况下具有疗效和安全性。在这篇叙述性综述中，我们旨在评估在接受艾美赛珠单抗预防且产生抑制物的甲型血友病患者中使用aPCC进行出血管理的证据，以及其他NFTs的相关证据。这些新出现的数据表明，在接受艾美赛珠单抗治疗且产生抑制物的患者中，以≤100 U/kg/天的剂量使用aPCC与血栓性微血管病或血栓事件无关。随着越来越多的NFTs可用于预防出血，两类BPAs对于有抑制物的患者的出血管理都是必需的。因此，最佳使用BPAs至关重要，这需要了解影响BPA选择的因素，如出血类型和部位、临床反应、给药剂量和使用持续时间、可及性和可用性，以及患者或护理人员的偏好。
