Cancer and Blood Diseases Institute, Division of Hematology, Cincinnati Children's Hospital Medical Center, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH.
Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Hematology Am Soc Hematol Educ Program. 2021 Dec 10;2021(1):469-477. doi: 10.1182/hematology.2021000281.
Hereditary hemorrhagic telangiectasia (HHT), the second most common inherited bleeding disorder, is associated with the development of malformed blood vessels. Abnormal blood vessels may be small and cutaneous or mucosal (telangiectasia), with frequent complications of bleeding, or large and visceral (arteriovenous malformations [AVMs]), with additional risks that can lead to significant morbidity and even mortality. HHT can present in many different ways and can be difficult to recognize, particularly in younger patients in the absence of a known family history of disease or epistaxis, its most common manifestation. HHT is commonly diagnosed using the established Curaçao clinical criteria, which include (1) family history, (2) recurrent epistaxis, (3) telangiectasia, and (4) visceral AVMs. Fulfillment of 3 or more criteria provides a definite diagnosis of HHT, whereas 2 criteria constitute a possible diagnosis of HHT. However, these criteria are insufficient in children to rule out disease due to the age-dependent development of some of these criteria. Genetic testing, when positive, can provide definitive diagnosis of HHT in all age groups. Clinical course is often complicated by significant epistaxis and/or gastrointestinal bleeding, leading to anemia in half of adult patients with HHT. The management paradigm has recently shifted from surgical approaches to medical treatments aimed at control of chronic bleeding, such as antifibrinolytic and antiangiogenic agents, combined with aggressive iron replacement with intravenous iron. Guidelines for management of HHT, including screening and treatment, were determined by expert consensus and originally published in 2009 with updates and new guidelines in 2020.
遗传性出血性毛细血管扩张症（HHT）是第二常见的遗传性出血性疾病，与畸形血管的形成有关。异常血管可能很小，呈皮肤或黏膜性（毛细血管扩张症），常伴有出血并发症，或很大，呈内脏性（动静脉畸形[AVM]），并有其他可能导致严重发病率甚至死亡率的风险。HHT 可以以许多不同的方式出现，并且很难识别，特别是在没有已知家族病史或疾病或鼻出血（其最常见的表现形式）的年轻患者中。HHT 通常使用既定的 Curaçao 临床标准进行诊断，其中包括 (1) 家族史、(2) 复发性鼻出血、(3) 毛细血管扩张症和 (4) 内脏 AVM。满足 3 项或更多标准可明确诊断为 HHT，而满足 2 项标准则可诊断为可能的 HHT。然而，由于这些标准中的一些在儿童时期会随着年龄的增长而发展，因此这些标准在儿童中不足以排除疾病。阳性的基因检测可在所有年龄段为 HHT 提供明确的诊断。由于频繁的鼻出血和/或胃肠道出血，导致一半的成年 HHT 患者出现贫血，因此临床病程常常变得复杂。管理模式最近已从针对某些患者的手术方法转变为旨在控制慢性出血的药物治疗，例如纤维蛋白溶解抑制剂和抗血管生成药物，同时结合静脉内铁剂进行积极的铁替代治疗。HHT 的管理指南，包括筛查和治疗，是由专家共识确定的，并于 2009 年首次发布，随后在 2020 年进行了更新和发布了新的指南。
