Treatment of Hereditary Hemorrhagic Telangiectasia Epistaxis

Stepwise Treatment Algorithm

The American Society of Hematology recommends beginning with moisturizing topical therapies, such as saline gels and humidification, to prevent epistaxis in patients with Hereditary Hemorrhagic Telangiectasia (HHT) 1, 2
Nasal moisturization is the foundation of epistaxis prevention through air humidification and topical application of saline solution or gels to reduce cracking and bleeding of fragile telangiectasias 3, 4

For epistaxis not responding to moisturizing therapies alone, oral tranexamic acid is now recommended as standard treatment, with a 17.3% reduction in epistaxis duration per month in 118 patients and a 54% reduction in composite epistaxis endpoints (duration and intensity) in 22 patients 1, 5, 4
Randomized controlled trials demonstrated no increase in thrombotic complications and hemoglobin improvement was not significant, though patients were not severely anemic at baseline 1

For moderate bleeding unresponsive to tranexamic acid, local ablative procedures, such as laser treatment and electrosurgery, are recommended before systemic antiangiogenics, with stronger evidence for laser treatment and electrosurgery 1, 2

For severe epistaxis failing moisturizing therapies, oral tranexamic acid, and/or local ablative therapies, systemic bevacizumab is now recommended, with a 50% relative reduction in mean epistaxis severity score (ESS) in the InHIBIT-Bleed study (238 patients with moderate-to-severe HHT bleeding) 1, 2, 5, 6
Systemic bevacizumab resulted in substantial improvements in hemoglobin, iron infusion needs, and red cell transfusion requirements, with a favorable safety profile and only 2% venous thromboembolism rate and no fatal adverse events 1, 2

Thalidomide downregulates VEGF levels and improves vascular wall integrity, with effectiveness documented in 67 patients across small studies, but its use is limited due to persistent peripheral neuropathy as an adverse event 1, 5

The treatment escalation is based on understanding that increased VEGF drives telangiectasia formation in HHT, and normalization of VEGF suppresses these anomalous vascular structures, explaining why systemic antiangiogenic therapy targeting VEGF (bevacizumab) is more effective than local destructive procedures 1, 2

Epistaxis in HHT can last hours per day and causes significant psychosocial morbidity, social isolation, and difficulties with employment, travel, and routine daily activities, and treatment decisions should prioritize reducing bleeding burden to improve these quality-of-life outcomes, not just hemoglobin levels 1, 3, 4, 8