Patients with HHT Exhibit More Severe Complications Than Previously Believed, With Hanny Al-Samkari, MD

Hereditary hemorrhagic telangiectasia (HHT) can result in substantially more frequent and significantly more severe complications than previously thought, according to an analysis of the Comprehensive HHT Outcomes Registry of the United States (CHORUS).1

These data were presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida, by Hanny Al-Samkari, MD, the Peggy S. Blitz Endowed Chair in hematology and oncology at the Massachusetts General Hospital and associate professor of medicine at Harvard Medical School.1

HHT is the second most common inherited bleeding disorder and is associated with the development of malformed blood vessels. These may be small and cutaneous or mucosal with frequent complications of bleeding, or large and visceral with additional risks that can lead to significant morbidity and mortality. HHT is also notoriously difficult to recognize, particularly in younger patients without a family history of disease or epistaxis.2

“For every man with hemophilia, there is ≥1 man and 1 woman with HHT – it’s twice as common as hemophilia, at least,” Al-Samkari told HCPLive in an exclusive interview. “There are no approved therapies for it. It’s been largely neglected in the hemostasis community – for the longest time, it was really just managed with procedures to treat bleeding, which is not the way to adequately address this disease, as we now know.”

CHORUS is a prospective, multicenter, longitudinal registry enrolling unselected patients with HHT. It contains >2400 data elements, which were collected by trained research coordinators at enrollment and follow-up visits via medical records and direct participant interviews for the purpose of Al-Samkari’s and colleagues’ study.1

Investigators included a total of 600 participants with either genetically- or Curacao-criteria-confirmed HHT from November 2023 to April 2025, across 15 HHT centers in the US. Median age was 53 years (range, 0-88), and 60% of patients were female. Most diagnoses were made during mid-to-late adulthood, despite most patients typically displaying manifestations of HHT by age 13.1

A total of 568 patients (95%) developed recurrent spontaneous epistaxis, with 339 (60%) developing recurrent epistaxis before age 13. 43% had ≥1 nasal surgery/procedure and 22% had ≥1 medical therapy for epistaxis, such as antifibrinolytic or antiangiogenic. 180 (30%) had a known diagnosis of chronic GI bleeding. Among post-menarche female patients, 124 (34%) had been diagnosed with heavy menstrual bleeding. 247 (41%) reported other clinically significant mucocutaneous oral or skin bleeding.1

454 patients (76%) had developed moderate-to-severe HHT-associated mucocutaneous bleeding, which was defined as an Epistaxis Severity Score >4, bleeding requiring targeted pharmaceutical or surgical intervention, intravenous iron, and/or red cell transfusion. This included 334 (56%) with moderate-to-severe HHT-associated epistaxis.1

Additionally, 408 patients (68%) had been diagnosed with anemia (n = 351; 59%) or iron deficiency (n = 381; 64%). Of these, 247 (61%) and 150 (37%) required intravenous iron and red blood cell transfusion, respectively. Venous and arterial thromboembolism occurred in 44 (7%) and 38 (6%) patients, respectively, including 34 (6%) with ischemic stroke.1

Solid organ AVMs, including brain, pulmonary, and liver, were diagnosed in 81 (15%), 268 (45%), and 128 (21%) patients, respectively. Only 30 with brain AVMs (37%) were diagnosed by age 25. Finally, 16 patients (3%) suffered ≥1 intracranial hemorrhage, with 10 (63%) suffering a first intracranial hemorrhage by age 25. 13 (2%) suffered ≥1 pulmonary hemorrhage.1

Regarding other serious complications, heart failure occurred in 41 patients (7%), pulmonary hypertension in 44 (7%), chronic liver disease in 17 (2.8%), epilepsy in 24 (4%), severe bacterial/deep-seated tissue infection in 35 (6%), and brain abscess in 15 (3%). Serious manifestations occurred in 128 (21%) of patients, and 241 (40%) required emergency room visits and/or hospital admissions for HHT complications.1

“These very concerning manifestations, particularly intracranial hemorrhage, can affect people while they’re young,” Al-Samkari said. “Most intracranial hemorrhages in HHT occur before age 25, and the average age of diagnosis was about 37 years. It’s a very concerning diagnostic delay, which we knew was present in HHT, but this study really raised the stakes of just how problematic that delay is.”

Editor’s Note: Al-Samkari reports disclosures with Pharmacosmos, Agios, Amgen, Vaderis, Novartis, Sobi, and others.

References

1. Al-Samkari H, Friday C, Kasthuri R, et al. Clinical spectrum of hereditary hemorrhagic telangiectasia (HHT): Data from the comprehensive HHT outcomes registry of the United States (CHORUS). Abstract presented at the 67th American Society of Hematology Annual Meeting. Orlando, FL. December 6-9.

2. Hammill AM, Wusik K, Kasthuri RS. Hereditary hemorrhagic telangiectasia (HHT): a practical guide to management. Hematology Am Soc Hematol Educ Program. 2021;2021(1):469-477. doi:10.1182/hematology.2021000281