Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia

Publication Date: September 7, 2020
Last Updated: March 14, 2022

Recommendations

Epistaxis management

The expert panel recommends that patients with HHT-related epistaxis use moisturizing topical therapies that humidify the nasal mucosa to reduce epistaxis. (S, M, )
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The expert panel recommends that clinicians consider the use of oral tranexamic acid for the management of epistaxis that does not respond to moisturizing topical therapies. (S, H, )
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The expert panel recommends that clinicians should consider ablative therapies for nasal telangiectasias, including laser treatment, radiofrequency ablation, electrosurgery, and sclerotherapy, in patients that have failed to respond to moisturizing topical therapies. (W, M, )
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The expert panel recommends that clinicians consider the use of systemic antiangiogenic agents for the management of epistaxis that has failed to respond to moisturizing topical therapies, ablative therapies, and/or tranexamic acid. (S, M, )
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The expert panel recommends that clinicians consider a septodermoplasty for patients whose epistaxis has failed to respond sufficiently to moisturizing topical therapies, ablative therapies, and/or tranexamic acid. (W, L, )
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The expert panel recommends that clinicians consider a nasal closure for patients whose epistaxis has failed to respond sufficiently to moisturizing topical therapies, ablative therapies, and/or tranexamic acid. (S, M, )
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The expert panel recommends that physicians advise patients with HHT-related epistaxis to use agents that humidify the nasal mucosa to prevent epistaxis. (W, , III)
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The expert panel recommends that clinicians refer HHT patients with epistaxis and who desire treatment to otorhinolaryngologists with HHT expertise for evaluation and treatment. (W, , III)
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The expert panel recommends that when considering nasal surgery for reasons other than epistaxis, the patient and clinician obtain consultation from an otorhinolaryngologist with expertise in HHT-related epistaxis. (W, , III)
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The expert panel recommends that the treatment for acute epistaxis requiring intervention include packing with material or products that have a low likelihood of causing rebleeding with removal (e.g., lubricated low-pressure pneumatic packing). (W, , III)
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GI bleeding management

The expert panel recommends esophagogastroduodenoscopy as the first-line diagnostic test for suspected HHT-related bleeding. Patients who meet colorectal cancer screening criteria and patients with SMAD4-HHT (genetically proven or suspected) should also undergo colonoscopy. (S, L, )
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The expert panel recommends considering capsule endoscopy for suspected HHT-related bleeding when esophagogastroduodenoscopy does not reveal significant HHT-related telangiectasia. (S, L, )
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The expert panel recommends that clinicians grade the severity of HHT-related GI bleeding and proposes the following framework:
  • Mild HHT-related GI bleeding: patient who meets their hemoglobin goals‡ with oral iron replacement
  • Moderate HHT-related GI bleeding: patient who meets their hemoglobin goals* with intravenous iron treatment
  • Severe HHT-related GI bleeding: patient who does not meet their hemoglobin goals‡ despite adequate iron replacement or requires blood transfusions.
(S, L, )

* Hemoglobin goals should reflect age, gender, symptoms and comorbidities.

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The expert panel recommends that endoscopic argon plasma coagulation be only used sparingly during endoscopy. (W, L, )
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The expert panel recommends that clinicians consider treatment of mild HHT-related GI bleeding with oral antifibrinolytics. (W, L, )
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The expert panel recommends that clinicians consider treatment of moderate to severe HHT-related GI bleeding with intravenous bevacizumab or other systemic antiangiogenic therapy. (S, M, )
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Anemia and anticoagulation

The expert panel recommends that the following HHT patients be tested for iron deficiency and anemia:
  • All adults, regardless of symptoms
  • All children with recurrent bleeding and/or symptoms of anemia
(S, H, )
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The expert panel recommends iron replacement for treatment of iron deficiency and anemia as follows:
  • Initial therapy with oral iron
  • Intravenous iron replacement for patients in whom oral is not effective, not absorbed, or not tolerated, or who are presenting with severe anemia
(S, M, )
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The expert panel recommends red blood cell transfusions in the following settings:
  • Hemodynamic instability/shock
  • Comorbidities that require a higher hemoglobin target
  • Need to increase the hemoglobin acutely, such as prior to surgery or during pregnancy
  • Inability to maintain an adequate hemoglobin despite frequent iron infusions
(S, L, )
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The expert panel recommends considering evaluation for additional causes of anemia in the setting of an inadequate response to iron replacement. (S, L, )
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The expert panel recommends that HHT patients receive anticoagulation (prophylactic or therapeutic) or antiplatelet therapy when there is an indication, with consideration of their individualized bleeding risks; bleeding in HHT is not an absolute contraindication for these therapies. (S, L, )
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The panel recommends avoiding the use of dual antiplatelet therapy and/or combination of antiplatelet therapy and anticoagulation, where possible, in patients with HHT. (W, L, )
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Liver VMs in HHT

The expert panel recommends that screening for liver VMs be offered to adults with definite or suspected HHT. (W, L, )
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The expert panel recommends diagnostic testing for liver VMs in HHT patients with symptoms and/or signs suggestive of complicated liver VMs (including heart failure, pulmonary hypertension, abnormal cardiac biomarkers, abnormal liver function tests, abdominal pain, portal hypertension, or encephalopathy), using Doppler ultrasound, multiphase contrast CT scan, or contrast abdominal MRI for diagnostic assessment of liver VMs. (S, H, )
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The expert panel recommends an intensive first-line management only for patients with complicated and/or symptomatic liver VMs, tailored to the type of liver VM complication(s). The expert panel recommends that HHT patients with high-output cardiac failure and pulmonary hypertension be comanaged by the HHT Center of Excellence and an HHT cardiologist or a pulmonary hypertension specialty clinic. (S, M, )
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The expert panel recommends that clinicians estimate prognosis of liver VMs using available predictors, to identify patients in need of closer monitoring. (S, M, )
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The expert panel recommends considering intravenous bevacizumab for patients with symptomatic high-output cardiac failure due to liver VMs who have failed to respond sufficiently to first-line management. (S, M, )
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The expert panel recommends referral for consideration of liver transplantation for patients with symptomatic complications of liver VMs, specifically refractory high-output cardiac failure, biliary ischemia, or complicated portal hypertension. (S, M, )
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The expert panel recommends that liver biopsy be avoided in any patient with proven or suspected HHT. (S, , III)
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The expert panel recommends that hepatic artery embolization be avoided in patients with liver VMs as it is only a temporizing procedure associated with significant morbidity and mortality. (S, , III)
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Pediatric care

The expert panel advises that diagnostic genetic testing be offered for asymptomatic children of a parent with HHT. (S, H, )
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The expert panel recommends screening for pulmonary AVMs in asymptomatic children with HHT or at risk for HHT at the time of presentation/diagnosis. (S, M, )
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The expert panel recommends that large pulmonary AVMs and pulmonary AVMs associated with reduced oxygen saturation be treated in children to avoid serious complications. (S, M, )
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The expert panel recommends repeating pulmonary AVM screening in asymptomatic children with HHT or at risk for HHT, typically at 5-year intervals. (S, L, )
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The expert panel recommends screening for brain VM in asymptomatic children with HHT or at risk for HHT, at the time of presentation/ diagnosis. (S, L, )
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The expert panel recommends that brain VMs with high-risk features be treated. (S, L, )
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Pregnancy and delivery

The expert panel recommends that clinicians discuss preconception and prenatal diagnostic options, including preimplantation genetic diagnosis, with HHT-affected individuals. (S, VL, )
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The expert panel recommends testing with unenhanced MRI in pregnant women with symptoms suggestive of brain VMs.. (S, VL, )
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The expert panel recommends that pregnant women with HHT who have not been recently screened and/or treated for pulmonary AVM should be approached as follows:

  • In asymptomatic patients, initial pulmonary AVM screening should be performed using either agitated saline transthoracic contrast echocardiography (TTCE) or low-dose noncontrast chest CT, depending on local expertise. Chest CT, when performed, should be done early in the second trimester.
  • In patients with symptoms suggestive of pulmonary AVM, diagnostic testing should be performed using low-dose noncontrast chest CT. This testing can be performed at any gestational age, as clinically indicated.
  • Pulmonary AVMs should be treated starting in the second trimester unless otherwise clinically indicated
(S, M, )
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The expert panel recommends that pregnant women with HHT be managed at a tertiary care center by a multidisciplinary team if they have untreated pulmonary AVMs and/or brain VMs or have not been recently screened for pulmonary AVMs. (S, VL, )
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The expert panel recommends not withholding an epidural because of a diagnosis of HHT, and that screening for spinal vascular malformations is not required. (S, L, )
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The expert panel recommends that women with known, non–high-risk brain VMs can labor and proceed with vaginal delivery. Patients may require an assisted second stage on a case-by-case basis. (S, M, )
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Diagnosis of HHT

The expert panel recommends that clinicians diagnose HHT using the Curaçao criteria or by identification of a causative mutation. (W, , III)
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The expert panel recommends that clinicians consider the diagnosis of HHT in patients with one or more Curaçao criteria. (W, , III)
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The expert panel recommends that asymptomatic children of a parent with HHT be considered to have possible HHT, unless excluded by genetic testing. (W, , III)
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The expert panel recommends that clinicians refer patients for diagnostic genetic testing for HHT:
  1. to identify the causative mutation in a family with clinically confirmed HHT;
  2. to establish a diagnosis in relatives of a person with a known causative mutation, including
    • individuals who are asymptomatic or minimally symptomatic and
    • individuals who desire prenatal testing; and
  3. to assist in establishing a diagnosis of HHT in individuals who do not meet clinical diagnostic criteria
(W, , III)
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The expert panel recommends that for individuals who test negative for ENG and ACVRL1 coding sequence mutations, SMAD4 testing should be considered to identify the causative mutation. (W, , III)
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Brain VMs

The expert panel recommends the use of MRI for brain VM screening in adults with possible or definite HHT using a protocol with and without contrast administration and using sequences that detect blood products, to maximize sensitivity. (W, , III)
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The expert panel recommends that adults presenting with an acute hemorrhage secondary to a brain VM be considered for definitive treatment in a center with neurovascular expertise.. (S, , III)
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The expert panel recommends that all other adults with brain VMs be referred to a center with neurovascular expertise to be considered for invasive testing and individualized management. (S, , III)
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The expert panel recommends that pregnant women with suspected or confirmed HHT harboring an asymptomatic brain VM during pregnancy have definitive treatment of their brain VM deferred until after delivery of their fetus. The expert panel recommends that the delivery of the fetus follow obstetrical principles. (W, , III)
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Pulmonary AVMs

The expert panel recommends that clinicians screen all patients with possible or confirmed HHT for pulmonary AVMs. (S, , III)
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The expert panel recommends that clinicians use transthoracic contrast echocardiography as the initial screening test for pulmonary AVM. (W, , II)
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The expert panel recommends that clinicians treat pulmonary AVMs with transcatheter embolotherapy. (S, , II)
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The expert panel recommends that clinicians provide the following long-term advice to patients with documented pulmonary AVMs (treated or untreated):
  1. Antibiotic prophylaxis for procedures with risk of bacteremia
  2. When IV access is in place, take extra care to avoid IV air
  3. Avoidance of SCUBA diving
(W, , III)
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The expert panel recommends that clinicians provide long-term follow-up for patients who have pulmonary AVMs, in order to detect growth of untreated pulmonary AVMs and also reperfusion of treated AVMs. (S, , II)
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AVM = arteriovenous malformation; CT = computed tomography; EGD = esophagogastroduodenoscopy; GI = gastrointestinal; HHT = hereditary hemorrhagic telangiectasia; IV = intravenous; MRI = magnetic resonance imaging; VM = vascular malformation.

Recommendation Grading

Overview

Title

Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia

Authoring Organization

Consensus and Physician Experts

Publication Month/Year

September 7, 2020

Last Updated Month/Year

February 6, 2024

Supplemental Implementation Tools

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Inclusion Criteria

Female, Male, Adolescent, Adult, Child, Older adult

Health Care Settings

Ambulatory, Hospital, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Diagnosis, Management

Diseases/Conditions (MeSH)

D013683 - Telangiectasia, Hereditary Hemorrhagic

Keywords

hereditary hemorrhagic telangiectasia, hereditary hemorrhagic telangiectasia (HHT), HHT, autosomal dominant disease, acute hemorrhage, chronic bleeding, vascular malformations

Supplemental Methodology Resources

Evidence Tables, Data Supplement

Methodology

Number of Source Documents
107
Literature Search Start Date
April 30, 2019
Literature Search End Date
May 31, 2019