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Management of hereditary hemorrhagic telangiectasia

Author
Claire Shovlin, PhD, FRCP
Section Editor
Lawrence LK Leung, MD
Deputy Editor
Jennifer S Tirnauer, MD

INTRODUCTION

Hereditary hemorrhagic telangiectasia (HHT; also called Osler-Weber-Rendu syndrome) is an autosomal dominant vascular disorder associated with a variety of clinical manifestations including mucocutaneous telangiectasia, epistaxis, gastrointestinal bleeding, and iron deficiency anemia. In addition, arteriovenous malformations (AVMs) commonly occur in the pulmonary, hepatic, and cerebral circulations, demanding knowledge of the risks and benefits of screening and treatment of patients with these complications.

The management of HHT will be reviewed here. The pathophysiology, epidemiology, and diagnosis of HHT are discussed in detail separately.

Additional discussions of pulmonary AVMs, which affect over half of individuals with HHT, are also discussed separately. (See "Pulmonary arteriovenous malformations: Epidemiology, etiology, and pathology in adults" and "Pulmonary arteriovenous malformations: Clinical features and diagnostic evaluation in adults" and "Therapeutic approach to adult patients with pulmonary arteriovenous malformations".)

OVERVIEW OF MANAGEMENT

Major management issues in individuals with HHT span the full range of clinical manifestations (table 1), and include the following [1-11]:

Patient education.

                            

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Literature review current through: Apr 2017. | This topic last updated: Jan 30, 2017.
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References
Top
  1. Shovlin CL. Hereditary haemorrhagic telangiectasia: pathophysiology, diagnosis and treatment. Blood Rev 2010; 24:203.
  2. Faughnan ME, Palda VA, Garcia-Tsao G, et al. International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia. J Med Genet 2011; 48:73.
  3. Geisthoff UW, Nguyen HL, Röth A, Seyfert U. How to manage patients with hereditary haemorrhagic telangiectasia. Br J Haematol 2015; 171:443.
  4. Garg N, Khunger M, Gupta A, Kumar N. Optimal management of hereditary hemorrhagic telangiectasia. J Blood Med 2014; 5:191.
  5. Shovlin CL. Circulatory contributors to the phenotype in hereditary hemorrhagic telangiectasia. Front Genet 2015; 6:101.
  6. Labeyrie PE, Courthéoux P, Babin E, et al. Neurological involvement in hereditary hemorrhagic telangiectasia. J Neuroradiol 2016; 43:236.
  7. Papaspyrou G, Schick B, Al Kadah B. Nd:YAG Laser Treatment for Extranasal Telangiectasias: A Retrospective Analysis of 38 Patients with Hereditary Hemorrhagic Telangiectasia and Review of the Literature. ORL J Otorhinolaryngol Relat Spec 2016; 78:245.
  8. Lacombe P, Lacout A, Marcy PY, et al. Diagnosis and treatment of pulmonary arteriovenous malformations in hereditary hemorrhagic telangiectasia: An overview. Diagn Interv Imaging 2013; 94:835.
  9. McDonald J, Bayrak-Toydemir P, Pyeritz RE. Hereditary hemorrhagic telangiectasia: an overview of diagnosis, management, and pathogenesis. Genet Med 2011; 13:607.
  10. Dupuis-Girod S, Bailly S, Plauchu H. Hereditary hemorrhagic telangiectasia: from molecular biology to patient care. J Thromb Haemost 2010; 8:1447.
  11. McDonald J, Pyeritz RE. Hereditary Hemorrhagic Telangiectasia. In: GeneReviews [Internet], Pagon RA, Adam MP, Ardinger HH, et al. (Eds), University of Washington, Seattle 2000.
  12. Lovering AT, Riemer RK, Thébaud B. Intrapulmonary arteriovenous anastomoses. Physiological, pathophysiological, or both? Ann Am Thorac Soc 2013; 10:504.
  13. Laurie SS, Elliott JE, Goodman RD, Lovering AT. Catecholamine-induced opening of intrapulmonary arteriovenous anastomoses in healthy humans at rest. J Appl Physiol (1985) 2012; 113:1213.
  14. Dupuis-Girod S, Ambrun A, Decullier E, et al. Effect of Bevacizumab Nasal Spray on Epistaxis Duration in Hereditary Hemorrhagic Telangectasia: A Randomized Clinical Trial. JAMA 2016; 316:934.
  15. Yin LX, Reh DD, Hoag JB, et al. The minimal important difference of the epistaxis severity score in hereditary hemorrhagic telangiectasia. Laryngoscope 2016; 126:1029.
  16. Whitehead KJ, Sautter NB, McWilliams JP, et al. Effect of Topical Intranasal Therapy on Epistaxis Frequency in Patients With Hereditary Hemorrhagic Telangiectasia: A Randomized Clinical Trial. JAMA 2016; 316:943.
  17. Silva BM, Hosman AE, Devlin HL, Shovlin CL. Lifestyle and dietary influences on nosebleed severity in hereditary hemorrhagic telangiectasia. Laryngoscope 2013; 123:1092.
  18. Elphick A, Shovlin CL. Relationships between epistaxis, migraines, and triggers in hereditary hemorrhagic telangiectasia. Laryngoscope 2014; 124:1521.
  19. Chamali B, Finnamore H, Manning R, et al. Dietary supplement use and nosebleeds in hereditary haemorrhagic telangiectasia - an observational study. Intractable Rare Dis Res 2016; 5:109.
  20. https://clinicaltrials.gov/ct2/show/NCT02930941.
  21. http://www.telangiectasia.co.uk/nopac.pdf.
  22. Lund VJ, Howard DJ. A treatment algorithm for the management of epistaxis in hereditary hemorrhagic telangiectasia. Am J Rhinol 1999; 13:319.
  23. Hitchings AE, Lennox PA, Lund VJ, Howard DJ. The effect of treatment for epistaxis secondary to hereditary hemorrhagic telangiectasia. Am J Rhinol 2005; 19:75.
  24. Kühnel TS, Wagner BH, Schurr CP, Strutz J. Clinical strategy in hereditary hemorrhagic telangiectasia. Am J Rhinol 2005; 19:508.
  25. Bergler W, Sadick H, Gotte K, et al. Topical estrogens combined with argon plasma coagulation in the management of epistaxis in hereditary hemorrhagic telangiectasia. Ann Otol Rhinol Laryngol 2002; 111:222.
  26. Folz BJ, Tennie J, Lippert BM, Werner JA. Natural history and control of epistaxis in a group of German patients with Rendu-Osler-Weber disease. Rhinology 2005; 43:40.
  27. Simonds J, Miller F, Mandel J, Davidson TM. The effect of bevacizumab (Avastin) treatment on epistaxis in hereditary hemorrhagic telangiectasia. Laryngoscope 2009; 119:988.
  28. Karnezis TT, Davidson TM. Efficacy of intranasal Bevacizumab (Avastin) treatment in patients with hereditary hemorrhagic telangiectasia-associated epistaxis. Laryngoscope 2011; 121:636.
  29. Livesey JA, Manning RA, Meek JH, et al. Low serum iron levels are associated with elevated plasma levels of coagulation factor VIII and pulmonary emboli/deep venous thromboses in replicate cohorts of patients with hereditary haemorrhagic telangiectasia. Thorax 2012; 67:328.
  30. Shovlin CL, Chamali B, Santhirapala V, et al. Ischaemic strokes in patients with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia: associations with iron deficiency and platelets. PLoS One 2014; 9:e88812.
  31. Devlin HL, Hosman AE, Shovlin CL. Antiplatelet and anticoagulant agents in hereditary hemorrhagic telangiectasia. N Engl J Med 2013; 368:876.
  32. Yaniv E, Preis M, Hadar T, et al. Antiestrogen therapy for hereditary hemorrhagic telangiectasia: a double-blind placebo-controlled clinical trial. Laryngoscope 2009; 119:284.
  33. Yaniv E, Preis M, Shevro J, et al. Anti-estrogen therapy for hereditary hemorrhagic telangiectasia - a long-term clinical trial. Rhinology 2011; 49:214.
  34. Shovlin CL, Jackson JE, Bamford KB, et al. Primary determinants of ischaemic stroke/brain abscess risks are independent of severity of pulmonary arteriovenous malformations in hereditary haemorrhagic telangiectasia. Thorax 2008; 63:259.
  35. Shovlin CL, Sulaiman NL, Govani FS, et al. Elevated factor VIII in hereditary haemorrhagic telangiectasia (HHT): association with venous thromboembolism. Thromb Haemost 2007; 98:1031.
  36. Gaillard S, Dupuis-Girod S, Boutitie F, et al. Tranexamic acid for epistaxis in hereditary hemorrhagic telangiectasia patients: a European cross-over controlled trial in a rare disease. J Thromb Haemost 2014; 12:1494.
  37. Geisthoff UW, Seyfert UT, Kübler M, et al. Treatment of epistaxis in hereditary hemorrhagic telangiectasia with tranexamic acid - a double-blind placebo-controlled cross-over phase IIIB study. Thromb Res 2014; 134:565.
  38. Hosman A, Westermann CJ, Snijder R, et al. Follow-up of Thalidomide treatment in patients with Hereditary Haemorrhagic Telangiectasia. Rhinology 2015; 53:340.
  39. Dupuis-Girod S, Ginon I, Saurin JC, et al. Bevacizumab in patients with hereditary hemorrhagic telangiectasia and severe hepatic vascular malformations and high cardiac output. JAMA 2012; 307:948.
  40. Sabbà C, Gallitelli M, Palasciano G. Efficacy of unusually high doses of tranexamic acid for the treatment of epistaxis in hereditary hemorrhagic telangiectasia. N Engl J Med 2001; 345:926.
  41. Saba HI, Morelli GA, Logrono LA. Brief report: treatment of bleeding in hereditary hemorrhagic telangiectasia with aminocaproic acid. N Engl J Med 1994; 330:1789.
  42. Sabbà C, Pasculli G, Cirulli A, et al. Rendu-Osler-Weber disease: experience with 56 patients. Ann Ital Med Int 2002; 17:173.
  43. Sargeant IR, Loizou LA, Rampton D, et al. Laser ablation of upper gastrointestinal vascular ectasias: long term results. Gut 1993; 34:470.
  44. Finnamore H, Le Couteur J, Hickson M, et al. Hemorrhage-adjusted iron requirements, hematinics and hepcidin define hereditary hemorrhagic telangiectasia as a model of hemorrhagic iron deficiency. PLoS One 2013; 8:e76516.
  45. Shovlin CL, Gilson C, Busbridge M, et al. Can Iron Treatments Aggravate Epistaxis in Some Patients With Hereditary Hemorrhagic Telangiectasia? Laryngoscope 2016; 126:2468.
  46. Shovlin CL, Patel T, Jackson JE. Embolisation of PAVMs reported to improve nosebleeds by a subgroup of patients with hereditary haemorrhagic telangiectasia. ERJ Open Res 2016; 2.
  47. Mollet IG, Patel D, Govani FS, et al. Low Dose Iron Treatments Induce a DNA Damage Response in Human Endothelial Cells within Minutes. PLoS One 2016; 11:e0147990.
  48. Santhirapala V, Williams LC, Tighe HC, et al. Arterial oxygen content is precisely maintained by graded erythrocytotic responses in settings of high/normal serum iron levels, and predicts exercise capacity: an observational study of hypoxaemic patients with pulmonary arteriovenous malformations. PLoS One 2014; 9:e90777.
  49. Gill SS, Roddie ME, Shovlin CL, Jackson JE. Pulmonary arteriovenous malformations and their mimics. Clin Radiol 2015; 70:96.
  50. Woodward CS, Pyeritz RE, Chittams JL, Trerotola SO. Treated pulmonary arteriovenous malformations: patterns of persistence and associated retreatment success. Radiology 2013; 269:919.
  51. Hsu CC, Kwan GN, Thompson SA, et al. Embolisation for pulmonary arteriovenous malformation. Cochrane Database Syst Rev 2012; :CD008017.
  52. Shovlin CL, Gibbs JS, Jackson JE. Management of pulmonary arteriovenous malformations in pulmonary hypertensive patients: a pressure to embolise? Eur Respir Rev 2009; 18:4.
  53. Shovlin CL, Tighe HC, Davies RJ, et al. Embolisation of pulmonary arteriovenous malformations: no consistent effect on pulmonary artery pressure. Eur Respir J 2008; 32:162.
  54. https://www.gov.uk/government/publications/the-never-events-list-for-2012-13.
  55. Shovlin C, Bamford K, Wray D. Post-NICE 2008: Antibiotic prophylaxis prior to dental procedures for patients with pulmonary arteriovenous malformations (PAVMs) and hereditary haemorrhagic telangiectasia. Br Dent J 2008; 205:531.
  56. European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu. EASL Clinical Practice Guidelines: Vascular diseases of the liver. J Hepatol 2016; 64:179.
  57. Buscarini E, Leandro G, Conte D, et al. Natural history and outcome of hepatic vascular malformations in a large cohort of patients with hereditary hemorrhagic teleangiectasia. Dig Dis Sci 2011; 56:2166.
  58. Vorselaars VM, Velthuis S, Snijder RJ, et al. Pulmonary hypertension in hereditary haemorrhagic telangiectasia. World J Cardiol 2015; 7:230.
  59. Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 2008; 29:2388.
  60. DeLeve LD, Valla DC, Garcia-Tsao G, American Association for the Study Liver Diseases. Vascular disorders of the liver. Hepatology 2009; 49:1729.
  61. Lerut J, Orlando G, Adam R, et al. Liver transplantation for hereditary hemorrhagic telangiectasia: Report of the European liver transplant registry. Ann Surg 2006; 244:854.
  62. Boillot O, Bianco F, Viale JP, et al. Liver transplantation resolves the hyperdynamic circulation in hereditary hemorrhagic telangiectasia with hepatic involvement. Gastroenterology 1999; 116:187.
  63. Dupuis-Girod S, Chesnais AL, Ginon I, et al. Long-term outcome of patients with hereditary hemorrhagic telangiectasia and severe hepatic involvement after orthotopic liver transplantation: a single-center study. Liver Transpl 2010; 16:340.
  64. Krowka MJ, Wiesner RH, Heimbach JK. Pulmonary contraindications, indications and MELD exceptions for liver transplantation: a contemporary view and look forward. J Hepatol 2013; 59:367.
  65. Flieger D, Hainke S, Fischbach W. Dramatic improvement in hereditary hemorrhagic telangiectasia after treatment with the vascular endothelial growth factor (VEGF) antagonist bevacizumab. Ann Hematol 2006; 85:631.
  66. Mitchell A, Adams LA, MacQuillan G, et al. Bevacizumab reverses need for liver transplantation in hereditary hemorrhagic telangiectasia. Liver Transpl 2008; 14:210.
  67. Oosting S, Nagengast W, de Vries E. More on bevacizumab in hereditary hemorrhagic telangiectasia. N Engl J Med 2009; 361:931; author reply 931.
  68. Maestraggi Q, Bouattour M, Toquet S, et al. Bevacizumab to Treat Cholangiopathy in Hereditary Hemorrhagic Telangiectasia: Be Cautious: A Case Report. Medicine (Baltimore) 2015; 94:e1966.
  69. Mohr JP, Parides MK, Stapf C, et al. Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial. Lancet 2014; 383:614.
  70. Yang W, Liu A, Hung AL, et al. Lower Risk of Intracranial Arteriovenous Malformation Hemorrhage in Patients With Hereditary Hemorrhagic Telangiectasia. Neurosurgery 2016; 78:684.
  71. http://www.arubastudy.org/ (Accessed on August 30, 2012).
  72. van Cutsem E, Rutgeerts P, Vantrappen G. Treatment of bleeding gastrointestinal vascular malformations with oestrogen-progesterone. Lancet 1990; 335:953.
  73. Sadick H, Bergler WF, Oulmi-Kagermann J, et al. Estriol induced squamous metaplasia on the nasal mucosa in patients with hereditary hemorrhagic telangiectasia. Arch Med Res 2005; 36:468.
  74. Bauditz J, Lochs H. Angiogenesis and vascular malformations: antiangiogenic drugs for treatment of gastrointestinal bleeding. World J Gastroenterol 2007; 13:5979.
  75. Bowcock SJ, Patrick HE. Lenalidomide to control gastrointestinal bleeding in hereditary haemorrhagic telangiectasia: potential implications for angiodysplasias? Br J Haematol 2009; 146:220.
  76. Lebrin F, Srun S, Raymond K, et al. Thalidomide stimulates vessel maturation and reduces epistaxis in individuals with hereditary hemorrhagic telangiectasia. Nat Med 2010; 16:420.
  77. de Gussem EM, Snijder RJ, Disch FJ, et al. The effect of N-acetylcysteine on epistaxis and quality of life in patients with HHT: a pilot study. Rhinology 2009; 47:85.
  78. Skaro AI, Marotta PJ, McAlister VC. Regression of cutaneous and gastrointestinal telangiectasia with sirolimus and aspirin in a patient with hereditary hemorrhagic telangiectasia. Ann Intern Med 2006; 144:226.
  79. Wheatley-Price P, Shovlin C, Chao D. Interferon for metastatic renal cell cancer causing regression of hereditary hemorrhagic telangiectasia. J Clin Gastroenterol 2005; 39:344.
  80. Spiekerkoetter E, Tian X, Cai J, et al. FK506 activates BMPR2, rescues endothelial dysfunction, and reverses pulmonary hypertension. J Clin Invest 2013; 123:3600.
  81. Hanneman K, Faughnan ME, Prabhudesai V. Cumulative radiation dose in patients with hereditary hemorrhagic telangiectasia and pulmonary arteriovenous malformations. Can Assoc Radiol J 2014; 65:135.
  82. NICE Clinical Knowledge Summaries (CKS): Interpreting ferritin levels. http://cks.nice.org.uk/anaemia-iron-deficiency#!diagnosissub:3.
  83. Shovlin CL, Awan I, Cahilog Z, et al. Reported cardiac phenotypes in hereditary hemorrhagic telangiectasia emphasize burdens from arrhythmias, anemia and its treatments, but suggest reduced rates of myocardial infarction. Int J Cardiol 2016; 215:179.
  84. Shovlin CL, Letarte M. Hereditary haemorrhagic telangiectasia and pulmonary arteriovenous malformations: issues in clinical management and review of pathogenic mechanisms. Thorax 1999; 54:714.
  85. Ference BA, Shannon TM, White RI Jr, et al. Life-threatening pulmonary hemorrhage with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia. Chest 1994; 106:1387.
  86. Shovlin CL, Winstock AR, Peters AM, et al. Medical complications of pregnancy in hereditary haemorrhagic telangiectasia. QJM 1995; 88:879.
  87. Shovlin CL, Sodhi V, McCarthy A, et al. Estimates of maternal risks of pregnancy for women with hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome): suggested approach for obstetric services. BJOG 2008; 115:1108.
  88. Arthur H, Geisthoff U, Gossage JR, et al. Executive summary of the 11th HHT international scientific conference. Angiogenesis 2015; 18:511.
  89. Govani FS, Shovlin CL. Hereditary haemorrhagic telangiectasia: a clinical and scientific review. Eur J Hum Genet 2009; 17:860.
  90. Ding D, Starke RM, Kano H, et al. International multicenter cohort study of pediatric brain arteriovenous malformations. Part 1: Predictors of hemorrhagic presentation. J Neurosurg Pediatr 2017; 19:127.
  91. Kjeldsen AD, Møller TR, Brusgaard K, et al. Clinical symptoms according to genotype amongst patients with hereditary haemorrhagic telangiectasia. J Intern Med 2005; 258:349.
  92. Letteboer TG, Mager JJ, Snijder RJ, et al. Genotype-phenotype relationship in hereditary haemorrhagic telangiectasia. J Med Genet 2006; 43:371.
  93. Sabbà C, Pasculli G, Lenato GM, et al. Hereditary hemorrhagic telangiectasia: clinical features in ENG and ALK1 mutation carriers. J Thromb Haemost 2007; 5:1149.
  94. Lesca G, Olivieri C, Burnichon N, et al. Genotype-phenotype correlations in hereditary hemorrhagic telangiectasia: data from the French-Italian HHT network. Genet Med 2007; 9:14.
  95. Bossler AD, Richards J, George C, et al. Novel mutations in ENG and ACVRL1 identified in a series of 200 individuals undergoing clinical genetic testing for hereditary hemorrhagic telangiectasia (HHT): correlation of genotype with phenotype. Hum Mutat 2006; 27:667.
  96. Bayrak-Toydemir P, McDonald J, Markewitz B, et al. Genotype-phenotype correlation in hereditary hemorrhagic telangiectasia: mutations and manifestations. Am J Med Genet A 2006; 140:463.
  97. Jelsig AM, Tørring PM, Kjeldsen AD, et al. JP-HHT phenotype in Danish patients with SMAD4 mutations. Clin Genet 2016; 90:55.
  98. Ganesan V, Robertson F, Berg J. Neurovascular screening in hereditary haemorrhagic telangiectasia: dilemmas for the paediatric neuroscience community. Dev Med Child Neurol 2013; 55:405.
  99. Kmietowicz Z. Computed tomography in childhood and adolescence is associated with small increased risk of cancer. BMJ 2013; 346:f3348.
  100. Mathews JD, Forsythe AV, Brady Z, et al. Cancer risk in 680,000 people exposed to computed tomography scans in childhood or adolescence: data linkage study of 11 million Australians. BMJ 2013; 346:f2360.
  101. McDonald J, Wooderchak-Donahue W, VanSant Webb C, et al. Hereditary hemorrhagic telangiectasia: genetics and molecular diagnostics in a new era. Front Genet 2015; 6:1.
  102. Gershon AS, Faughnan ME, Chon KS, et al. Transcatheter embolotherapy of maternal pulmonary arteriovenous malformations during pregnancy. Chest 2001; 119:470.
  103. Cottin V, Plauchu H, Bayle JY, et al. Pulmonary arteriovenous malformations in patients with hereditary hemorrhagic telangiectasia. Am J Respir Crit Care Med 2004; 169:994.
  104. Heald B, Rigelsky C, Moran R, et al. Prevalence of thoracic aortopathy in patients with juvenile Polyposis Syndrome-Hereditary Hemorrhagic Telangiectasia due to SMAD4. Am J Med Genet A 2015; 167A:1758.
  105. Ahmedzai S, Balfour-Lynn IM, Bewick T, et al. Managing passengers with stable respiratory disease planning air travel: British Thoracic Society recommendations. Thorax 2011; 66 Suppl 1:i1.
  106. Mason CG, Shovlin CL. Flight-related complications are infrequent in patients with hereditary haemorrhagic telangiectasia/pulmonary arteriovenous malformations, despite low oxygen saturations and anaemia. Thorax 2012; 67:80.
  107. Kjeldsen A, Aagaard KS, Tørring PM, et al. 20-year follow-up study of Danish HHT patients-survival and causes of death. Orphanet J Rare Dis 2016; 11:157.
  108. Donaldson JW, McKeever TM, Hall IP, et al. The UK prevalence of hereditary haemorrhagic telangiectasia and its association with sex, socioeconomic status and region of residence: a population-based study. Thorax 2014; 69:161.
  109. Donaldson JW, McKeever TM, Hall IP, et al. Complications and mortality in hereditary hemorrhagic telangiectasia: A population-based study. Neurology 2015; 84:1886.
  110. Hosman AE, Devlin HL, Silva BM, Shovlin CL. Specific cancer rates may differ in patients with hereditary haemorrhagic telangiectasia compared to controls. Orphanet J Rare Dis 2013; 8:195.
  111. Duarte CW, Black AW, Lucas FL, Vary CP. Cancer incidence in patients with hereditary hemorrhagic telangiectasia. J Cancer Res Clin Oncol 2017; 143:209.
  112. Hosman AE, Shovlin CL. Cancer and hereditary haemorrhagic telangiectasia. J Cancer Res Clin Oncol 2017; 143:369.