-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

592 A Multicenter Study of Safety, Tolerability, and Effectiveness of Antithrombotic Therapy in Hereditary Hemorrhagic TelangiectasiaClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 322. Disorders of Coagulation or Fibrinolysis: Clinical and Epidemiological: Von Willebrand Disease and Other Congenital and Acquired Bleeding Disorders
Hematology Disease Topics & Pathways:
Research, Bleeding and Clotting, bleeding disorders, Anticoagulant Drugs, adult, Clinical Practice (Health Services and Quality), Non-Biological therapies, elderly, Clinical Research, health outcomes research, Diseases, Therapies, Adverse Events, young adult , Study Population, Human
Sunday, December 11, 2022: 5:15 PM

Zain M Virk, MD1*, Ellen Zhang, BA2*, Josanna Rodriguez-Lopez, MD3*, Alison Witkin, MD3*, Alexandra Wong, MD3*, Jay Luther, MD4*, Angela Lin, MD5*, Mingming Ning, MD6*, Eric F. Grabowski, MD, DSc7, Eric Holbrook, MD8* and Hanny Al-Samkari, MD9

1Vanderbilt University Medical Center, Nashville, TN
2Harvard Medical School, Boston, MA
3Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA
4Division of Gastroenterology and Hepatology, Massachusetts General Hospital, Boston, MA
5Department of Pediatrics, Massachusetts General Hospital, Boston, MA
6Department of Neurology, Massachusetts General Hospital, Boston, MA
7Cardiovascular Thrombosis Laboratory, Massachusetts General Hospital, Boston, MA
8Division of Rhinology, Massachusetts Eye and Ear Institute, Boston, MA
9Division of Hematology Oncology, Massachusetts General Hospital, Cambridge, MA

Introduction: With a prevalence of 1 in 5000 persons, hereditary hemorrhagic telangiectasia (HHT) is the second-most common hereditary bleeding disorder in the world. As HHT is a bleeding disorder with a concomitant elevated thrombotic risk, antithrombotic therapy (anticoagulation and antiplatelet therapy) is frequently needed, but data describing its use is extremely limited. Antithrombotic therapy recommendations in the recently published Second International HHT Guidelines are based on this very limited data (largest prior cohort study including 28 patients) or expert opinion alone.

Methods: We evaluated outcomes in a 5-hospital observational cohort study of adults with HHT receiving antithrombotic therapy over a 26-year period. Patients were identified via electronic database query, and eligibility was confirmed and data collection performed via manual chart review. Multivariable logistic modeling was used to assess for predictors of premature antithrombotic therapy discontinuation and hematologic characteristics and healthcare utilization before and after initiation of antithrombotic therapy were evaluated using paired t-tests (continuous data) and chi-square tests (categorical data).


Patients and Episodes: 119 HHT patients with 187 discrete antithrombotic therapy episodes were included. Median (range) age was 70 (27-92) years and 69 patients (58%) were female. Most common antithrombotic indications were venous thromboembolism (61 episodes), coronary artery disease (29 episodes), and atrial fibrillation (29 episodes). Most common antithrombotic agents used (by number of episodes) were aspirin (57), warfarin (35), low molecular weight heparin (26), apixaban (15), rivaroxaban (8), and multiple simultaneous medications (41).

Tolerability and Effectiveness Overall and by Antithrombotic Therapy Class: 59 patients (50%) prematurely discontinued and/or dose-reduced therapy (including 52 patients [44%] who discontinued) due to worsening bleeding. Initiation at reduced dose-intensity had a similar premature discontinuation rate (49%) as initiation at standard dose-intensity (43%). Difficulty receiving indicated therapy may have resulted in increased thromboembolic recurrence (20 patients, 17%). Rates of dose-reduction and/or premature discontinuation were similar regardless of anticoagulant class (warfarin, 46%; heparin-based, 48%; direct oral anticoagulant [DOAC], 44%) or with multiple simultaneous agents (44%) but slightly lower with single-agent antiplatelet therapy (37%).

Predictors of Therapy Discontinuation: In a multivariable logistic model, a history of GI bleeding was associated with 3.25-fold odds of discontinuation (P=0.001, Figure).

Adverse Events Associated with Antithrombotic Therapy: Hemoglobin was significantly lower (10.8 g/dL vs 12.2 g/dL, P<0.001), and need for intravenous iron and RBC transfusion significantly higher (29 patients vs 12 patients, P=0.004), in the 3 months after antithrombotic therapy initiation versus the 3 months before (Table); number of patients requiring ED visits and/or hospital admissions due to bleeding also increased. 75 patients (63%) developed worsened epistaxis (of whom 33% dose-reduced or discontinued antithrombotic therapy due to epistaxis) and 44 patients (37%) developed newly-diagnosed or worsened gastrointestinal bleeding (of whom 59%, dose-reduced or discontinued antithrombotic therapy due to GI bleeding).

Conclusions: Successful administration of antithrombotic therapy is challenging in HHT, resulting in objectively higher morbidity and healthcare utilization from worsened bleeding. Discontinuation rates approached 50% regardless of dose-intensity at initiation or type of antithrombotic agent used and were higher in patients with a history of gastrointestinal bleeding. These findings, from the largest and most comprehensive evaluation of antithrombotic therapy in HHT to date, challenge at least two recommendations made based on limited prior data or expert opinion alone in the Second International HHT Guidelines: the recommendation for use of warfarin or heparin-based therapy over DOACs and the avoidance of multiple simultaneous agents even when otherwise indicated due to concern for higher bleeding risk.

Disclosures: Rodriguez-Lopez: Bayer: Consultancy, Research Funding; United Therapeutics: Consultancy, Research Funding; Altavant Sciences: Consultancy; Merck: Research Funding. Holbrook: Lyra Therapeutics: Consultancy. Al-Samkari: argenx: Consultancy; Novartis: Consultancy; Moderna: Consultancy; Dova: Consultancy, Research Funding; Forma: Consultancy; Rigel: Consultancy; Amgen: Research Funding; Sobi: Consultancy, Research Funding; Agios: Consultancy, Research Funding.

*signifies non-member of ASH