What is the primary treatment approach for Osler (Hereditary Hemorrhagic Telangiectasia) syndrome?

Primary Treatment Approach for Hereditary Hemorrhagic Telangiectasia (HHT)

The primary treatment for HHT follows a stepwise escalation algorithm: begin with nasal moisturization using saline gels and humidification, escalate to oral tranexamic acid (35-65 mg elemental iron daily with dose adjustment based on response) if epistaxis remains inadequately controlled, then proceed to local ablative therapies (laser, electrosurgery, sclerotherapy), and reserve systemic bevacizumab (5 mg/kg IV every 2 weeks for 4-6 doses) for severe refractory cases that fail all prior interventions. 1

Initial Management: Nasal Moisturization

• Start all HHT patients with air humidification and topical saline solution or gels applied to nasal mucosa to prevent cracking and bleeding of fragile telangiectasias 1
• This reduces mucosal trauma but often proves inadequate as monotherapy for most patients with significant epistaxis 1
• Use resorbable packing materials specifically for HHT patients to reduce rebleeding risk during packing removal 2, 1

Second-Line: Oral Tranexamic Acid

• Prescribe oral tranexamic acid when moisturization alone fails to control epistaxis 1
• This produces a 17.3% reduction in epistaxis duration and 54% reduction in composite epistaxis endpoints 1, 3
• The Second International HHT Guidelines now recommend tranexamic acid as standard treatment based on two randomized controlled trials from 2014 1

Third-Line: Local Ablative Therapies

• Proceed to laser treatment, electrosurgery, or sclerotherapy when medical management fails 1, 4
• Sclerotherapy of telangiectasias, including in-office applications, has proven safe and effective 4
• These procedures target individual bleeding sites directly 5

Fourth-Line: Systemic Bevacizumab

• Reserve systemic bevacizumab for severe epistaxis or gastrointestinal bleeding failing all prior interventions 1
• Administer 5 mg/kg IV every 2 weeks for 4-6 doses, then maintenance every 1-3 months 1
• This produces a 50% reduction in epistaxis severity score and mean hemoglobin improvement of 3.2 g/dL 1

Essential Concurrent Management

Iron Replacement Therapy

• Test all adults with HHT for iron deficiency and anemia regardless of symptoms 1
• Start with oral iron (35-65 mg elemental iron daily), escalating dose or frequency if inadequate response 1
• Switch to intravenous iron for patients with inadequate absorption, intolerance, or severe anemia 1
• Reassess at 1 month for adequate response (hemoglobin rise ≥1.0 g/dL, normalization of ferritin and transferrin saturation) 1

Mandatory Organ Screening

• Perform Doppler ultrasonography as first-line imaging for liver involvement in all HHT patients 2, 1
• Screen all HHT patients for pulmonary arteriovenous malformations using contrast echocardiography or chest CT, as these can be treated presymptomatically to prevent stroke and cerebral abscess 1
• Obtain brain MRI to detect cerebral vascular malformations, as nearly one in five HHT patients develop stroke or cerebral abscess 1
• Consider upper endoscopy to evaluate for gastrointestinal telangiectasias, especially in patients with unexplained anemia disproportionate to epistaxis severity 1

Critical Pitfalls to Avoid

• Never perform liver biopsy in any patient with proven or suspected HHT due to catastrophic hemorrhage risk 2, 1
• Do not focus solely on hemoglobin levels—treatment decisions should prioritize quality of life, as epistaxis causes significant psychosocial morbidity, social isolation, and difficulties with employment, travel, and routine daily activities 1
• Avoid dual antiplatelet therapy and combination antiplatelet/anticoagulation therapy where possible, as these significantly increase bleeding risk 6
• For patients requiring anticoagulation, prefer heparin agents or vitamin K antagonants over direct oral anticoagulants (DOACs), as DOACs may be less well tolerated due to increased bleeding risk 6

Multidisciplinary Coordination

• Refer all patients diagnosed with HHT to a multidisciplinary team with expertise in HHT management 2, 1
• Patients with SMAD4 mutations require additional surveillance for juvenile polyposis with upper GI tract surveillance every 1-3 years starting at age 18 years 1
• All patients with SMAD4 pathogenic variants must be managed in conjunction with a specialist HHT center with experience in evaluating and managing both HHT and juvenile polyposis complications 1

Treatment Philosophy

• The fundamental pathology involves enlarged vessels with thin walls that are prone to rupture and bleeding throughout multiple organ systems 2, 3
• There is no curative treatment—all management is symptomatic and aimed at reducing bleeding complications and preventing life-threatening sequelae from arteriovenous malformations 7, 8
• Quality of life should drive treatment decisions, not just laboratory values, given the profound psychosocial impact of recurrent bleeding 1