Hereditary Hemorrhagic Telangiectasia: Diagnosis and Modern Management of the Most Common Inherited Bleeding Disorder

| 23 September 2024

Written by Leah Stanley MSc' 26 (Candidate)

On September 12th, 2024, Dr. Hanny Al-Samkari, a guest speaker from Harvard Medical School and Massachusetts General Hospital, was welcomed at Medical Grand Rounds. Dr. Al-Samkari gave the Department of Medicine a fascinating presentation titled “Hereditary Hemorrhagic Telangiectasia: Diagnosis and Modern Management of the Second Most Common Inherited Bleeding Disorder.”

Dr. Al-Samkari described Hereditary Hemorrhagic Telangiectasia (HHT) as a structural problem of the vascular system, where angiogenesis (the formation of new blood vessels) is impaired. When angiogenesis is compromised, blood vessels cannot retain all the components of blood.1 The abnormal blood vessels are fragile and often burst, causing blood to escape from the circulatory system in what is known as a hemorrhage.1-2 Specifically, HHT is characterized by lesions known as arteriovenous malformations (AVMs), where blood passes quickly from arteries to veins, bypassing the normal capillary network. AVMs may form in the liver, lungs, brain, mouth, gut, face and fingers, disrupting blood flow and oxygen circulation.

Since HHT is inherited, it is readily passed down through families. Diagnosis is primarily based on symptoms, confirmed with genetic testing to identify the altered gene. Common symptoms include nosebleeds, migraines, iron deficiency anemia, heavy menstrual bleeding, and abnormal red marks on the face, hands and tongue. There is a lack of societal understanding of these symptoms, resulting in the underdiagnosis of HHT. In North America, HHT affects approximately 1:10,000 people, which is likely an underestimate.3 Symptoms are underrecognized, therefore HHT may present in multiple generations of a family before a diagnosis is confirmed.

There is no cure for HHT, and symptoms worsen without intervention. Dr. Al-Samkari highlighted how HHT negatively impacts quality of life, particularly due to nosebleeds, which often interfere with work, school, and relationships. Psychological comorbidities, such as anxiety and depression are common due to severe nosebleeds.

Current research focuses on repurposing drugs approved for other diseases, such as cancer. Furthermore, intravenous iron supplementation is required to treat iron deficiency anemia, associated with HHT. Dr. Al-Samkari cautioned against ferric carboxymaltose due to the risk of bone fractures. Instead, he promoted traditional methods such as ferric gluconate.

In a discussion with TMED students, Dr. Al-Samkai told a striking story of a man who was diagnosed with HHT in his 30’s, with three children. Although the children were experiencing symptoms, the family did not suspect an inherited bleeding disorder until the man’s AVMs became extremely severe. This story emphasized the need for public awareness of HTT and the importance of genetic testing for all family members of the diagnosed individual. Furthermore, Dr. Al-Samkai discussed how there is an equity issue for women with inherited bleeding disorders, contrasting the significant financial investment in hemophilia (which predominantly affects men) with the lack of investment into HTT (which affects women equally, or more than men).

In conclusion, Dr. Al-Samkai is a passionate and dedicated clinician-scientist who strives to completely turn around the lives of patients affected by HTT. On a final note, Dr. Al-Samkai’s advised TMED students to “do something you sincerely enjoy”, leaving the class inspired.

References

Benoit Ho-Tin-Noé, Yacine Boulaftali, Eric Camerer; Platelets and vascular integrity: how platelets prevent bleeding in inflammation. Blood 2018; 131 (3): 277–288. doi: https://doi.org/10.1182/blood-2017-06-742676

About Hereditary Hemorrhagic Telangiectasia (HHT). Hereditary Hemorrhagic Telangiectasia (HHT). Published June 18, 2024. https://www.cdc.gov/hht/about/index.html#:~:text=HHT%20is%20a%20genetic%20disorder,even%20among%20affected%20family%20members.

McDonald J, Stevenson DA. Hereditary hemorrhagic telangiectasia. GeneReviews® - NCBI Bookshelf. Published November 24, 2021. https://www.ncbi.nlm.nih.gov/books/NBK1351/