What are the guideline sources, guidelines and references for Hereditary hemorrhagic telangiectasia ?
Guideline sources The following summarized guidelines for the evaluation and management of hereditary hemorrhagic telangiectasia are prepared by our editorial team based on guidelines from the Hereditary Haemorrhagic Telangiectasia Working Group (HHT-WG 2020), the American College of Gastroenterology (ACG 2020; 2015), and the European Association for the Study of the Liver (EASL 2016). 1 2 3 4 Calculator Cura ao Criteria for hereditary h Guidelines https://web.pathway.md/diseases/rec7GXA0GMsYiIKiE 1/7 6/24/23, 12:41 PM Hereditary hemorrhagic telangiectasia Pathway 1. Screening and diagnosis Indications for screening: As per HHT-WG 2020 guidelines, screen asymptomatic children of a parent with HHT for HHT with genetic testing. A As per ACG 2015 guidelines, consider screening SMAD4 mutation carriers for HHT. C Diagnosis: As per HHT-WG 2020 guidelines, diagnose HHT using the Cura ao criteria or by identification of a causative mutation. B Show 2 more As per EASL 2016 guidelines, suspect the diagnosis of HHT in patients with diffuse liver VMs (either complicated or not). B 2. Classification and risk stratification Severity grading: Grade the severity of HHT-related gastrointestinal bleeding according to the following framework (Hgb goals should reflect age, gender, symptoms, and comorbidities): Situation Guidance Hgb goal is met with oral iron Mild Hgb goal is met with IV iron Moderate Hgb goal is not met despite adequate iron replacement, or blood transfusions are required. B Severe Prognostic assessment: estimate the prognosis of liver VMs using available predictors to identify patients requiring closer monitoring. B 3. Diagnostic investigations Genetic testing: Refer patients for genetic testing for HHT: to identify the causative mutation in a family with clinically confirmed HHT to establish the diagnosis in relatives of a patient with a known causative mutation, including asymptomatic or minimally symptomatic patients and patients desiring prenatal testing to assist establishing the diagnosis in patients not meeting clinical diagnostic criteria. B Consider SMAD4 testing to identify the causative mutation in patients tested negative for ENG and ACVRL1 coding sequence mutations. C https://web.pathway.md/diseases/rec7GXA0GMsYiIKiE 2/7 6/24/23, 12:41 PM Hereditary hemorrhagic telangiectasia Pathway Diagnostic imaging: As per HHT-WG 2020 guidelines, consider obtaining contrast TTE as initial screening test for pulmonary AVMs. C Show 2 more As per EASL 2016 guidelines, obtain Doppler ultrasound as first-line imaging for the diagnosis and staging of liver VMs. Obtain multiphase CT to investigate symptomatic liver VMs if Doppler ultrasound is unavailable. A Show 2 more Evaluation for vascular malformations, liver: As per ACG 2020 guidelines, do not obtain routine screening for liver VMs in patients with HHT. Insufficient evidence to support that making a diagnosis in an asymptomatic patient has clinical benefits or prevents death. D Show 3 more As per HHT-WG 2020 guidelines, offer screening for liver VMs in adult patients with definite or suspected HHT. B Evaluation for vascular malformations (pulmonary): screen all patients with possible or confirmed HHT for pulmonary AVMs. B Show 3 more Evaluation for vascular malformations (brain): Consider screening for brain VMs with MRI in adult patients with possible or definite HHT using a protocol with and without contrast administration and using sequences that detect blood products, to maximize sensitivity. C Screen for brain VMs at the time of presentation/diagnosis of asymptomatic pediatric patients with HHT or at risk for HHT. B Evaluation for iron deficiency and anemia: Test the following patients with HHT for iron deficiency and anemia: all adult patients, regardless of symptoms all pediatric patients with recurrent bleeding and/or symptoms of anemia. A Consider evaluating for additional causes of anemia in the setting of an inadequate response to iron replacement. B 4. Diagnostic procedures Upper and lower gastrointestinal endoscopy: perform upper gastrointestinal endoscopy as first- line diagnostic modality in patients with suspected HHT-related bleeding. B Show 2 more Liver biopsy: As per EASL 2016 guidelines: Avoid performing liver biopsy for the diagnosis of hepatic VMs related to HHT. D https://web.pathway.md/diseases/rec7GXA0GMsYiIKiE 3/7 6/24/23, 12:41 PM Hereditary hemorrhagic telangiectasia Pathway Acknowledge the risk of increased bleeding with percutaneous transcapsular liver biopsy when liver biopsy is pursued for other reasons. A 5. Medical management Topical therapies for epistaxis: advise using moisturizing topical therapies that humidifying the nasal mucosa to reduce epistaxis in patients with HHT-related epistaxis. B Anticoagulation and antiplatelet therapy: Administer anticoagulation (prophylactic or therapeutic) or antiplatelet therapy when indicated in patients with HHT with consideration of their individualized bleeding risks. Be aware that bleeding in HHT is not an absolute contraindication for these therapies. B Avoid dual antiplatelet therapy and/or combination of antiplatelet therapy and anticoagulation where possible in patients with HHT. D Antifibrinolytic therapy: Consider administering oral tranexamic acid for the management of epistaxis not responding to moisturizing topical therapies in patients with HHT. B Consider administering oral antifibrinolytics for the treatment of patients with mild HHT-related gastrointestinal bleeding. C Antiangiogenic therapy: Consider administering systemic antiangiogenic agents for the management of epistaxis in patients with HHT failed to respond to moisturizing topical therapies, ablative therapies, and/or tranexamic acid. B Consider administering IV bevacizumab or other systemic antiangiogenic agents for the management of patients with moderate-to-severe HHT-related gastrointestinal bleeding. B Iron replacement: Offer iron replacement for the treatment of patients with HHT and iron deficiency/anemia as follows: initial therapy with oral iron IV iron replacement when oral is not effective, not absorbed, or not tolerated, or in severe anemia. B Consider evaluating for additional causes of anemia in the setting of an inadequate response to iron replacement. B 6. Therapeutic procedures Red blood cell transfusion: Perform RBC transfusions in patients with HHT in the following settings: hemodynamic instability/shock comorbidities requiring a higher Hgb target https://web.pathway.md/diseases/rec7GXA0GMsYiIKiE 4/7 6/24/23, 12:41 PM Hereditary hemorrhagic telangiectasia Pathway need to increase the Hgb acutely, such as before surgery or during pregnancy inability to maintain an adequate Hgb despite frequent iron infusions. B Endoscopic argon plasma coagulation: perform endoscopic argon plasma coagulation in patients with HHT only during endoscopy. B Transcatheter embolotherapy: As per HHT-WG 2020 guidelines, perform transcatheter embolotherapy for the treatment of pulmonary AVMs in patients with HHT. B As per EASL 2016 guidelines, seek advice from a medical team with expertise in HHT before making any decisions regarding the treatment of liver VMs, and notably orthotopic liver transplantation. A Show 2 more 7. Surgical interventions Surgical management of epistaxis (ablative therapies): consider performing ablative therapies for nasal telangiectasias, including laser treatment, radiofrequency ablation, electrosurgery, and sclerotherapy, in patients with HHT failed to respond to moisturizing topical therapies. C Surgical management of epistaxis (septodermoplasty): consider performing septodermoplasty for the management of epistaxis in patients with HHT failed to sufficiently respond to moisturizing topical therapies, ablative therapies, and/or tranexamic acid. C Surgical management of epistaxis (nasal closure): consider performing nasal closure for the management of epistaxis in patients with HHT failed to sufficiently respond to moisturizing topical therapies, ablative therapies, and/or tranexamic acid. B Liver transplantation: As per HHT-WG 2020 guidelines, refer patients with HHT with symptomatic complications of liver VMs, specifically with refractory high-output HF, biliary ischemia, or complicated portal hypertension, for consideration of liver transplantation. B As per EASL 2016 guidelines, seek advice from a medical team with expertise in HHT before making any decisions regarding the treatment of liver VMs, and notably orthotopic liver transplantation. A Show 2 more 8. Specific circumstances Patients with vascular malformations, liver: As per ACG 2020 guidelines, offer standard medical therapy for each complication of liver VMs in patients with HHT, which results in symptom resolution in the majority. B Show 4 more https://web.pathway.md/diseases/rec7GXA0GMsYiIKiE 5/7 6/24/23, 12:41 PM Hereditary hemorrhagic telangiectasia Pathway As per HHT-WG 2020 guidelines, estimate the prognosis of liver VMs using available predictors to identify patients requiring closer monitoring. B Show 4 more Patients with vascular malformations (pulmonary): perform transcatheter embolotherapy for the treatment of pulmonary AVMs in patients with HHT. B Show 3 more Patients with vascular malformations (brain): consider providing definitive treatment for adult patients presenting with an acute hemorrhage secondary to a brain VM, in a center with neurovascular expertise. B Show 2 more Pregnant patients: As per ACG 2020 guidelines, pay special attention in female patients with HHT and liver VMs becoming pregnant, due to anticipated hemodynamic stress. B As per HHT-WG 2020 guidelines, obtain unenhanced MRI in pregnant patients with symptoms suggestive of brain VMs. B Show 5 more Pediatric patients: offer genetic testing for HHT in asymptomatic children of a parent with HHT. A Show 6 more 9. Patient education Preconception and prenatal counseling: discuss preconception and prenatal diagnostic options, including preimplantation genetic diagnosis, with patients with HHT. B References 1. Marie E Faughnan, Johannes J Mager, Steven W Hetts et al. Second International Guidelines for the Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia. Ann Intern Med. 2020 Dec 15;173 12 989 1001. Open 2. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Vascular diseases of the liver. J Hepatol. 2016 Jan;64 1 179 202. Open 3. Douglas A Simonetto, Ashwani K Singal, Guadalupe Garcia-Tsao et al. ACG Clinical Guideline: Disorders of the Hepatic and Mesenteric Circulation. Am J Gastroenterol. 2020 Jan;115 1 18 40. Open 4. Sapna Syngal, Randall E Brand, James M Church et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015 Feb;110 2 223 62; quiz 263. Open 5. Andrew M Ferry, Alex E Wright, Gwen Baillargeon et al. Epidemiology and Trends of Hereditary Hemorrhagic Telangiectasia in the United States. Am J Rhinol Allergy. 2020 Mar;34 2 230 237. Open https://web.pathway.md/diseases/rec7GXA0GMsYiIKiE 6/7 6/24/23, 12:41 PM Hereditary hemorrhagic telangiectasia Pathway 6. Athena Kritharis, Hanny Al-Samkari, David J Kuter. Hereditary hemorrhagic telangiectasia: diagnosis and management from the hematologist's perspective. Haematologica. 2018 Sep;103 9 1433 1443. Open 7. James W Donaldson, Tricia M McKeever, Ian P Hall et al. Complications and mortality in hereditary hemorrhagic telangiectasia: A population-based study. Neurology. 2015 May 5;84 18 1886 93. Open 8. C L Shovlin, A E Guttmacher, E Buscarini et al. Diagnostic criteria for hereditary hemorrhagic telangiectasia Rendu-Osler-Weber syndrome). Am J Med Genet. 2000 Mar 6;91 1 66 7. Open 9. Italian Association for the Study of the Liver AISF , Italian Association for the Study of the Liver AISF. AISF position paper on liver disease and pregnancy. Dig Liver Dis. 2016 Feb;48 2 120 37. Open https://web.pathway.md/diseases/rec7GXA0GMsYiIKiE 7/7