Clinical spectrum of hereditary hemorrhagic telangiectasia: data from the Comprehensive HHT Outcomes Registry of the US (CHORUS)
Abstract
Abstract Hereditary hemorrhagic telangiectasia (HHT), an autosomal dominant vasculopathy affecting 1 in 5000 individuals, is the second most common inherited bleeding disorder worldwide. Despite this prevalence, comprehensive data on disease manifestations and complications remain limited. To address this gap, the US Congress allocated funding leading to the Comprehensive HHT Outcomes Registry of the United States (CHORUS), a prospective, 15-center longitudinal registry enrolling unselected patients with confirmed HHT. In this initial report, we describe findings from the first 600 participants, with a median age of 53 (range, 0-88) years and 60% female. Despite most participants developing typical HHT manifestations by age 13 years, the majority (63%) were not diagnosed until mid-to-late adulthood. Recurrent spontaneous epistaxis occurred in 95% of participants, chronic gastrointestinal bleeding in 30%, and heavy menstrual bleeding in 35% of postmenarche females, together resulting in moderate-to-severe mucosal bleeding in 76%. Iron deficiency and/or anemia were diagnosed in 68%, with 41% requiring IV iron and 25% requiring red cell transfusions. Serious complications of solid-organ arteriovenous malformations were frequent, including intracranial hemorrhage (3%), pulmonary hemorrhage (2%), venous thromboembolism (7%), arterial thromboembolism (11%), heart failure (7%), and pulmonary hypertension (7%). These data from CHORUS, the first national US registry of its kind, provide reliable, real-world estimates of the incidence, prevalence, and severity of numerous HHT manifestations and complications. HHT has a high burden of moderate-to-severe bleeding, anemia, thrombosis, and major neurologic and cardiopulmonary complications. There is a mean interval between first symptoms and diagnosis of >2 decades, during which substantial, serious, and preventable HHT morbidity, including early intracranial hemorrhage, may occur. This trial was registered at clinicaltrials.gov as NCT06259292.
Article Details
Authors (43)
Hanny Al-Samkari
Department of Medicine, Massachusetts General Hospital, Boston
Cassi Friday
2Cure HHT, Monkton, MD
Raj S. Kasthuri
3Division of Hematology/Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC
James R. Gossage
4Division of Pulmonary and Critical Care Medicine, Augusta University, Augusta, GA
Charles G. Murphy
Peter Hountras
6Division of Pulmonary and Critical Care Medicine, University of Colorado Anschutz, Aurora, CO
Karen L. Smith
3Division of Hematology/Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC
Kristi Kirkland
3Division of Hematology/Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC
Vivek Iyer
Vikas Prasad
8Department of Medicine, Mayo Clinic, Rochester, MN
Vaibhav Ahluwalia
Nazareth Hospital, Philadelphia, Pennsylvania, United States
Josanna Rodriguez-Lopez
9Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA
Alison S. Witkin
9Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA
Miles Conrad
10Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA
Steven Hetts
11Division of Neuroendovascular Surgery, University of California, San Francisco, San Francisco, CA
Michael Ohliger
10Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA
Murali Chakinala
12Division of Pulmonary and Critical Care Medicine, Washington University in St. Louis, St. Louis, MO
Bryan A. Sisk
13Division of Pediatric Hematology and Oncology, Washington University in St. Louis, St. Louis, MO
Melissa A. Beasley
14Department of Medicine, Washington University in St. Louis, St. Louis, MO
Paul Kirkpatrick
4Division of Pulmonary and Critical Care Medicine, Augusta University, Augusta, GA
Jonathan Lindquist
John T. Battaile
An Lu
16Division of Pulmonary and Critical Care Medicine, University of Texas Southwestern, Dallas, TX
Joseph Parambil
17Division of Pulmonary, Allergy, and Critical Care Medicine, Cleveland Clinic, Cleveland, OH
Keith McCrae
18Division of Hematology/Oncology, Cleveland Clinic, Cleveland, OH
Vladimir Sheynzon
19Department of Radiology, Columbia University, New York, NY
Kevin Whitehead
CHILDRENS HOSP PHILADELPHIA, Philadelphia, Pennsylvania, United States
Cassidy Sion
20Division of Cardiovascular Medicine, University of Utah, Salt Lake City, UT
Justin McWilliams
21Department of Radiology, University of California, Los Angeles, Los Angeles, CA
Lucas R. Cusumano
21Department of Radiology, University of California, Los Angeles, Los Angeles, CA
Scott O. Trerotola
22Department of Radiology, University of Pennsylvania, Philadelphia, PA
Theodore G. Drivas
Mark Chesnutt
24Division of Pulmonary, Allergy, and Critical Care Medicine, Oregon Health and Science University, Portland, OR
Claire Kaufman
25Department of Radiology, Oregon Health and Science University, Portland, OR
Melissa Dickey
21Department of Radiology, University of California, Los Angeles, Los Angeles, CA
Danielle Boyce
2Cure HHT, Monkton, MD
Nolie Krock
2Cure HHT, Monkton, MD
Crystal Cottrill
2Cure HHT, Monkton, MD
Tania Competiello
2Cure HHT, Monkton, MD
Hara Levy
26Division of Pulmonology and Sleep Medicine, University of Wisconsin-Madison, Madison, WI
Marianne Clancy
2Cure HHT, Monkton, MD
Katharine Henderson
27Division of Clinical Radiology, Yale University, New Haven, CT
Jeffrey S. Pollak
27Division of Clinical Radiology, Yale University, New Haven, CT