Systemic Antiangiogenic Therapies for Bleeding in Hereditary Hemorrhagic Telangiectasia: A Practical, Evidence-Based Guide for Clinicians

Abstract

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.

2023 Eberhard F. Mammen Award Announcements: Part I—Most Popular Articles

“…Hanny Al-Samkari was also a 2020 Young Investigator Award winner, 31 and his article also represents the submission provided as a condition of the award. 23 As always, I always get considerable satisfaction in announcing these awards. This year once again saw the topic of COVID-19 take prominence, not only worldwide but also in this journal.…”

“…Hanny Al-Samkari was also a 2020 Young Investigator Award winner, 31 and his article also represents the submission provided as a condition of the award. 23…”

Multidisciplinary coordinated care of hereditary hemorrhagic telangiectasia (Osler–Weber–Rendu disease)

“…Therapy for suspected GI bleeding is based on the magnitude of the blood loss and is defined as (1) mild bleeding and hemoglobin maintained on oral iron; (2) moderate bleeding and hemoglobin maintained with IV iron; and (3) severe bleeding and unable to maintain hemoglobin with iron therapy and/or needs transfusions. 7,49,50 Treatment for mild suspected GI bleeding is oral antifibrinolytic agents. The use of systemic antiangiogenic therapy is considered for moderate to severe GI bleeding in conjunction with endoscopic therapy, and this is presented in the hematology section of this review.…”

2022 Eberhard F. Mammen Award Announcements: Part II—Young Investigator Awards

“…The most recent arising publications are also listed in the reference list for the benefit of the readership. 3 4 5 6 7 8 9 10 11 12 13 I have mentioned several times my personal gratification that most of the papers from earlier years have subsequently appeared in several annual top 100 listings. Of further interest, some of these papers or the young investigators themselves have subsequently won one of the Most Popular awards (see Table 1 for a list of prior editorials on these awards).…”