HHT: More Common Than Hemophilia, Yet Still Widely Missed

A 38-year-old Iraq War veteran with pallor and fatigue experienced 3 to 5 nosebleeds weekly, including occasional gushers. He also had low hemoglobin levels, black and tarry stools, and a family history of nosebleeds.

Running tired him out, and he developed shortness of breath. The patient also had small red spots sprinkled over his face, lips, tongue, and a couple tips of his fingers.

These symptoms include several hallmarks of hereditary hemorrhagic telangiectasia (HHT), a genetic bleeding disorder that is more common than clinicians may realize, said hematologist Hanny Al-Samkari, MD, an associate professor with Harvard Medical School and Massachusetts General Hospital. He spoke to colleagues during a recent webinar on rare and ultrarare blood disorders sponsored by the Association of VA Hematology/Oncology (AVAHO).

The condition is uncommon but not extremely rare, affecting 1 in 5000 people—making it more common than hemophilia (1 in 10,000), Al-Samkari said. Still, HHT is often undetected, and patients typically wait 27 years to receive a diagnosis.

“If anybody in the audience hasn’t seen a patient with HHT, it’s not because you haven’t seen one,” Al-Samkari said. “You've seen one. It's just that it wasn’t clear they had HHT when you saw them.”

Manifestations of HHT

HHT is a progressive bleeding disorder caused by abnormal blood vessel formation. Dilated blood vessels in areas such as mucous membranes cause chronic gastrointestinal hemorrhage, tiny red spots (like the veteran had) and severe recurrent nose bleeds (epistaxis).

“There is no disease that causes epistaxis in humans like HHT,” Al-Samkari explained.

HHT also causes blood vessel malformations in the lungs, liver, brain, and other organs that can contribute to:

• High-output cardiac failure
• Liver disease and cirrhosis (the patient’s mother died of liver disease aged 50 years)
• Pulmonary hypertension and hemorrhage • Migraine headaches, heart failure, thromboembolism, aneurysm, and epilepsy
• Hemorrhagic stroke, transient ischemic attack, and sudden death (a cousin of the patient died suddenly aged 5 years of a supposed aneurysm)

Not surprisingly, patients have reduced overall survival compared to healthy counterparts.

New Data Reveal Extent of Complications

Al-Samkari highlighted the findings of the 2026 CHORUS study that he led, which included 600 patients in a prospective HHT registry (median age 53 years, 60% female). Most patients (63%) weren’t diagnosed until mid-to-late adulthood even though most had symptoms as early as when they were aged 13 years. Recurrent nosebleeds occurred in 95% of patients, gastrointestinal bleeding in 30%, and heavy menstrual bleeding in 35% of menstruation-age females. Iron deficiency and/or anemia were found in 68% overall. Serious complications included intracranial hemorrhage (3%), pulmonary hemorrhage (2%), venous thromboembolism (7%), arterial thromboembolism (11%), heart failure (7%), and pulmonary hypertension (7%).

Al-Samkari said patients should undergo several types of screening for arteriovenous malformations: echocardiogram with agitated saline contrast (“echo bubble study”) every few years; brain magnetic resonance imaging once, unless symptoms warrant more screening; and liver imaging such as Doppler ultrasound.

Treatment Pearls: Boosting Iron Levels

There are no US Food and Drug Administration-approved treatments for HHT, but therapies can help. Al-Samkari, who wrote about his HHT protocols in Blood in 2024, offered tips about treating the disorder. The recommended level for ferritin is > 50 ng/mL and > 20% for transferrin saturation. If patients are under these levels, Al-Samkari considers that a trigger for iron infusion. Oral iron is usually not enough except in cases of mild bleeding. Most patients will need intravenous (IV) iron infusion. There are several possible IV iron formulations, he said, but ferric carboxymaltose must be avoided due to potential adverse effects.

Al-Samkari offered recommendations about medication therapy and procedures for patients with HHT:

• Acute, unstable bleeding: IV anti-fibrinolytics
• Chronic, stable, and mild bleeding: either tranexamic acid (3-4 g daily) in 2-3 divided doses or ε-aminocaproic acid (3-4 g daily) in divided doses
• Chronic, stable, and moderate bleeding: Tranexamic acid or ε-aminocaproic acid; clinical trials of novel agents; systemic pomalidomide in nosebleed-predominant cases (2-4 mg daily); bevacizumab in gastrointestinal bleeding-predominant (5 mg/kg infusions)
• Chronic, stable, and severe bleeding: Clinical trial, pomalidomide, or bevacizumab.

Al-Samkari discloses relationships with Agios, Amgen, Alnylam, Sobi, Sanofi, Argenx, Pharmacosmos, Novartis, Alpine, Diagonal, Vaderis, and Terremoto.