Department of Medicine, Division of Hematology, University of North Carolina, Chapel Hill, NC.
Hematology Am Soc Hematol Educ Program. 2021 Dec 10;2021(1):219-225. doi: 10.1182/hematology.2021000253.
Hemophilia A (HA) and B are inherited bleeding disorders caused by a deficiency of factor VIII or factor IX, respectively. The current standard of care is the administration of recombinant or purified factor. However, this treatment strategy still results in a high economic and personal burden to patients, which is further exacerbated by the development of inhibitors-alloantibodies to factor. The treatment landscape is changing, with nonfactor therapeutics playing an increasing role in what we consider to be the standard of care. Emicizumab, a bispecific antibody that mimics the function of factor VIIIa, is the first such nonfactor therapy to gain US Food and Drug Administration approval and is rapidly changing the paradigm for HA treatment. Other therapies on the horizon seek to target anticoagulant proteins in the coagulation cascade, thus "rebalancing" a hemorrhagic tendency by introducing a thrombotic tendency. This intricate hemostatic balancing act promises great things for patients in need of more treatment options, but are these other therapies going to replace factor therapy? In light of the many challenges facing these therapies, should they be viewed as a replacement of our current standard of care? This review discusses the background, rationale, and potential of nonfactor therapies as well as the anticipated pitfalls and limitations. This is done in the context of a review of our current understanding of the many aspects of the coagulation system.
血友病 A（HA）和 B 是分别由因子 VIII 或因子 IX 缺乏引起的遗传性出血性疾病。目前的标准治疗方法是给予重组或纯化的因子。然而，这种治疗策略仍然给患者带来了很高的经济和个人负担，而抑制剂-同种抗体的产生进一步加剧了这种负担。治疗领域正在发生变化，非因子治疗药物在我们认为的标准治疗中发挥着越来越重要的作用。Emicizumab 是一种双特异性抗体，可模拟因子 VIIIa 的功能，是第一种获得美国食品和药物管理局批准的此类非因子治疗药物，正在迅速改变 HA 的治疗模式。其他即将出现的治疗方法旨在靶向凝血级联中的抗凝蛋白，从而通过引入血栓形成倾向来“重新平衡”出血倾向。这种复杂的止血平衡作用为需要更多治疗选择的患者带来了巨大的希望，但这些其他治疗方法会取代因子治疗吗？鉴于这些治疗方法面临的许多挑战，它们是否应该被视为对我们当前标准治疗的替代？本文讨论了非因子治疗方法的背景、原理和潜力，以及预期的陷阱和局限性。这是在回顾我们目前对凝血系统许多方面的理解的背景下进行的。
