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Hereditary hemorrhagic telangiectasia: diagnosis and management from
the hematologist’s perspective
Ferrata Storti Foundation
Athena Kritharis,1 Hanny Al-Samkari2 and David J Kuter2
1Division of Blood Disorders, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ and 2Hematology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
ABSTRACT
Hereditary hemorrhagic telangiectasia (HHT), also known as Osler- Weber-Rendu syndrome, is an autosomal dominant disorder that causes abnormal blood vessel formation. The diagnosis of hered- itary hemorrhagic telangiectasia is clinical, based on the Curaçao criteria. Genetic mutations that have been identified include ENG, ACVRL1/ALK1, and MADH4/SMAD4, among others. Patients with HHT may have telangiectasias and arteriovenous malformations in various organs and suffer from many complications including bleeding, anemia, iron deficiency, and high-output heart failure. Families with the same mutation exhibit considerable phenotypic variation. Optimal treatment is best delivered via a multidisciplinary approach with appropriate diag- nosis, screening and local and/or systemic management of lesions. Antiangiogenic agents such as bevacizumab have emerged as a promis- ing systemic therapy in reducing bleeding complications but are not cur- ative. Other pharmacological agents include iron supplementation, antifibrinolytics and hormonal treatment. This review discusses the biol- ogy of HHT, management issues that face the practising hematologist, and considerations of future directions in HHT treatment.
Introduction
Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber- Rendu syndrome, is a common autosomal dominant disorder that causes abnormal blood vessel formation.1 The eponym recognizes the 19th century physicians William Osler, Henri Jules Louis Marie Rendu, and Frederick Parkes Weber, who each independently described the disease.2 Clinical sequelae of HHT include muco- cutaneous telangiectasias, arteriovenous malformations (AVMs), and bleeding, with consequent iron deficiency anemia. Patients with HHT have been found to have abnormal plasma concentrations of transforming growth factor-beta (TGF-β)3 and vascular endothelial growth factor (VEGF)4 secondary to mutations in ENG, ACVRL1 and MADH4.5 There is considerable inter- and intra-family variation in disease onset and clinical severity, even in cases resulting from an identical muta- tion. Iron deficiency and associated anemia are frequent complications of the dis- ease due to recurrent epistaxis and/or gastrointestinal bleeding. There are no accepted guidelines on management of patients with HHT beyond supportive measures of iron supplementation, red cell transfusion, and directed treatments to ablate bleeding sites and AVMs.
Bevacizumab, a recombinant humanized monoclonal antibody that blocks angiogenesis via VEGF inhibition, appears to be promising in HHT as an intra- venous formulation for reducing the frequency and severity of epistaxis and impacting quality of life.6,7 However, data on intranasal bevacizumab have been conflicting, and studies investigating the use of intravenous bevacizumab are lim- ited to case reports and retrospective series.8 Treatment of HHT involves a multi- disciplinary approach of specialists in cardiology, pulmonology, hepatology, inter- ventional radiology, ear, nose and throat (ENT), genetics, and hematology. This
Haematologica 2018 Volume 103(9):1433-1443
Correspondence:
hal-samkari@mgh.harvard.edu
Received: April 4, 2018. Accepted: May 14, 2018. Pre-published: May 24, 2018.
doi:10.3324/haematol.2018.193003
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/9/1433
©2018 Ferrata Storti Foundation
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