Division of Hematology Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Semin Thromb Hemost. 2022 Jul;48(5):514-528. doi: 10.1055/s-0042-1743467. Epub 2022 Feb 28.
Management of bleeding in hereditary hemorrhagic telangiectasia (HHT), the second most common hereditary bleeding disorder in the world, is currently undergoing a paradigm shift. Disease-modifying antiangiogenic therapies capable of achieving durable hemostasis via inducing telangiectasia regression have emerged as a highly effective and safe modality to treat epistaxis and gastrointestinal bleeding in HHT. While evidence to date is incomplete and additional studies are ongoing, patients presently in need are being treated with antiangiogenic agents off-label. Intravenous bevacizumab, oral pazopanib, and oral thalidomide are the three targeted primary angiogenesis inhibitors, with multiple studies describing both reassuring safety and impressive effectiveness in the treatment of moderate-to-severe HHT-associated bleeding. However, at present there is a paucity of guidance in the literature, including the published HHT guidelines, addressing the practical aspects of antiangiogenic therapy for HHT in clinical practice. This review article and practical evidence-based guide aims to fill this unaddressed need, synthesizing published data on the use of antiangiogenic agents in HHT, relevant data for their use outside of HHT, and expert guidance where evidence is lacking. After a brief review of principles of bleeding therapy in HHT, guidance on hematologic support with iron and blood products, and alternatives to antiangiogenic therapy, this article examines each of the aforementioned antiangiogenic agents in detail, including patient selection, initiation, monitoring, toxicity management, and discontinuation. With proper, educated use of antiangiogenic therapies in HHT, patients with even the most severe bleeding manifestations can achieve durable hemostasis with minimal side-effects, dramatically improving health-related quality of life and potentially altering the disease course.
遗传性出血性毛细血管扩张症（HHT）是世界上第二常见的遗传性出血性疾病，其出血的管理目前正在发生范式转变。能够通过诱导毛细血管扩张消退而实现持久止血的新型疾病修正抗血管生成治疗，已成为治疗 HHT 鼻出血和胃肠道出血的一种非常有效且安全的方式。尽管目前的证据并不完整，且仍有多项研究正在进行中，但目前有需要的患者正在接受抗血管生成药物的标签外治疗。静脉注射贝伐珠单抗、口服帕唑帕尼和口服沙利度胺是三种靶向原发性血管生成抑制剂，多项研究均描述了它们在治疗中重度 HHT 相关出血方面既安全又有效。然而，目前文献中缺乏相关指导，包括已发表的 HHT 指南，也没有针对 HHT 临床实践中抗血管生成治疗的实际方面提供指导。这篇综述文章和基于实践的循证指南旨在填补这一未满足的需求，综合了有关抗血管生成药物在 HHT 中的应用的已发表数据、HHT 以外相关用途的数据，以及在证据不足的情况下提供专家指导。本文简要回顾了 HHT 出血治疗的原则、铁和血液制品的血液支持以及抗血管生成治疗的替代方法，然后详细检查了上述每种抗血管生成药物，包括患者选择、起始、监测、毒性管理和停药。通过在 HHT 中正确、有教育意义地使用抗血管生成疗法，即使是出血症状最严重的患者也能实现持久止血，且副作用最小，极大地改善了生活质量，并可能改变疾病进程。
