Hereditary Hemorrhagic Telangiectasia
(Osler-Weber-Rendu Syndrome)
(See also Overview of Vascular Bleeding Disorders.)
More than 80% of patients have mutations in one of the following genes (1):
General reference
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1. Kritharis A, Al-Samkari H, Kuter D: Hereditary hemorrhagic telangiectasia: Diagnosis and management from the hematologist’s perspective. Haematologica 103:1433–1443, 2018. doi: 10.3324/haematol.2018.193003.
Symptoms and Signs
The most characteristic lesions of hereditary hemorrhagic telangiectasia are small red-to-violet telangiectatic lesions on the face, lips, oral and nasal mucosa, and tips of the fingers and toes. Similar lesions may be present throughout the mucosa of the gastrointestinal (GI) tract, resulting in recurrent GI bleeding. Patients may experience recurrent, profuse nosebleeds. Some patients have pulmonary arteriovenous malformations (AVMs). These AVMs may cause significant right-to-left shunts, which can result in dyspnea, fatigue, cyanosis, or erythrocytosis. However, the first sign of the presence of AVMs may be a brain abscess, transient ischemic attack, or stroke as a result of infected or noninfected emboli. Cerebral or spinal AVMs occur in some families and may cause subarachnoid hemorrhage, seizures, or paraplegia. Hepatic AVMs may lead to liver failure and high output heart failure. Chronic iron deficiency anemia is commonly present.
This photo shows a close-up of the face of a patient with multiple telangiectasias secondary to hereditary hemorrhagic telangiectasia.
Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) is an autosomal dominant disorder that manifests with widespread cutaneous, mucosal, and visceral telangiectases and arteriovenous malformations. Papular, punctate, and linear telangiectases occur predominantly on the tongue, lips, digit tips, perioral region, and trunk.
Diagnosis
Diagnosis of hereditary hemorrhagic telangiectasia is based on the finding of characteristic arteriovenous malformations on the face, mouth, nose, digits, and/or internal organs in the context of epistaxis and family history. The Curaçao criteria include the following:
Hereditary hemorrhagic telangiectasia is definite if 3 of these criteria are met and possible if 2 are met (1).
Endoscopy or angiography is sometimes needed. Laboratory findings are usually normal except for iron deficiency anemia in many patients.
Testing for the ENG, ACVRL1, and MADH4 mutations may be helpful in some patients with atypical features or for screening asymptomatic family members.
Screening
Diagnosis reference
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1. Shovlin CL, Guttmacher AE, Buscarini E, et al: Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). Am J Med Genet 91(1):66–67, 2000. doi: 10.1002/(sici)1096-8628(20000306)91:1<66::aid-ajmg12>3.0.co;2-p.
Treatment
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Sometimes laser ablation, surgical resection, or embolization of symptomatic arteriovenous malformations
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Supplemental iron therapy
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Possibly blood transfusions
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Sometimes antifibrinolytic drugs (eg, aminocaproic acid, tranexamic acid)
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Sometimes angiogenesis inhibitors (eg, bevacizumab, pomalidomide, thalidomide)
Treatment for most patients is supportive, but accessible telangiectasias (eg, in the nose or gastrointestinal tract via endoscopy) may be treated with laser ablation. Arteriovenous malformations may be treated by surgical resection or coil embolization.
Repeated blood transfusions may be needed; therefore, immunization with hepatitis B vaccine is important.
Many patients require continuous iron therapy to replace iron lost in repeated mucosal bleeding (see treatment of Iron Deficiency Anemia); many patients require parenteral iron and sometimes erythropoietin.
Treatment with drugs that inhibit fibrinolysis, such as aminocaproic acid or tranexamic acid, may be beneficial.
Treatment with drugs that inhibit angiogenesis such as bevacizumab, pomalidomide, or thalidomide can reduce the number and density of abnormal vessel growth (1). In addition, bevacizumab has recently been shown to reduce the incidence of nasal and gastrointestinal bleeding.
To avoid paradoxical embolization of particulate matter to the brain through pulmonary arteriovenous malformations, all IV fluids need to given through a filter.
Treatment reference
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1. Al-Samkari H, Kritharis A, Rodriguez-Lopez JM, Kuter D: Systemic bevacizumab for the treatment of chronic bleeding in hereditary haemorrhagic telangiectasia. J Intern Med 285(2):223–231, 2019. doi: 10.1111/joim.12832. Epub 2018 Oct 9.
Key Points
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Nasal and gastrointestinal telangiectasias may cause significant external hemorrhage.
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Vascular malformations in the central nervous system, lungs, and liver may bleed; hepatic and pulmonary malformations may cause significant shunting.
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Accessible mucosal telangiectasias and arteriovenous malformations may be treated with laser ablation; coil embolization or surgical resection may be needed for other vascular malformations.
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Antifibrinolytic drugs and angiogenesis inhibitors may reduce the incidence of bleeding.
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Many patients require parenteral iron supplements because of chronic blood loss.
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All IV solutions should be given through a filter to avoid paradoxical embolization of particulate matter to the brain through pulmonary arteriovenous malformations.
Drugs Mentioned In This Article
| Drug Name | Select Trade |
|---|---|
aminocaproic acid |
AMICAR |
tranexamic acid |
CYKLOKAPRON |
pomalidomide |
POMALYST |
bevacizumab |
AVASTIN |
thalidomide |
THALOMID |
