Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease, is one of the most common inherited bleeding disorders in the world, yet many people have never heard of it. People most frequently experience nosebleeds, though HHT is a complex bleeding and vascular disorder that has implications that go far beyond the nose.
Read on to learn more about what HHT is, how it affects the body, and why early diagnosis and treatment are so important.
What Is HHT and How Common Is it?
HHT is a genetic blood vessel disorder. Some capillaries develop abnormally, creating fragile connections that are prone to bleeding and other complications.
These fragile vessels can appear close to the surface of the skin or mucous membranes as tiny red spots (called telangiectasias) or as larger, deeper vascular malformations called arteriovenous malformations (AVMs) in major organs.
Hanny Al-Samkari, M.D., co-director of the HHT Center at Massachusetts General Hospital in Boston, says HHT affects an estimated 1 in 5,000 people and is the second most common genetic bleeding disorder in the U.S. and worldwide, with a prevalence roughly twice that of hemophilia. “For every man with hemophilia, there is approximately one woman and one man with HHT,” Al-Samkari says. “Strong evidence also suggests that HHT is the most severe inherited bleeding disorder of women.”
It’s also vastly underdiagnosed. The nonprofit advocacy group Cure HHT estimates that up to 80% of people with HHT don’t know that they have it, and the average delay in diagnosis is 27 years.
HHT is sometimes called the “great masquerader” because its symptoms can look like more familiar conditions such as iron-deficiency anemia, migraine, asthma, stroke, congestive heart failure, or liver disease. “Patients are often misdiagnosed as having von Willebrand disease as well, given the propensity for nosebleeding and heavy menstrual bleeding in HHT,” Al-Samkari says.
How HHT Can Put Major Organs at Risk
While nosebleeds are often the earliest and most visible symptom of HHT, the deeper concern lies in AVMs — abnormal connections between arteries and veins that bypass the normal capillary network. AVMs can develop in these critical organs:
- Lungs:Approximately 40% of people with HHT have AVMs in the lungs, according to Cure HHT. These AVMs can rupture, causing coughing up of blood or life-threatening lung bleeding (of special concern in pregnant women with HHT) and also can allow small blood clots or bacteria to pass directly into the bloodstream and travel to the brain, increasing the risk of stroke or brain abscess. Most pulmonary AVMs can be identified through screening and are treatable once found.
- Liver:Liver vascular malformations are present in roughly 75% of people with HHT, though noticeable symptoms are present only about 10% of the time. These types of malformations can strain the heart and lead to heart failure, liver disease and other complications.
- Brain:Brain vascular malformations affect approximately 15% of HHT patients and can sometimes rupture without warning, leading to bleeding in the brain. This is why experts recommend brain screening for anyone diagnosed with HHT, regardless of age.
Chronic Anemia and Internal Bleeding: The Hidden Burden of HHT
For many families, the most constant burden of HHT isn’t a dramatic event like a stroke but rather chronic blood loss. Roughly 95% of people with HHT experience recurring nosebleeds, often beginning in childhood or adolescence, that can range from merely a nuisance to severe episodes that take hours to stop, require emergency room intervention, and/or require a blood transfusion.
“It is quite common for patients with HHT to have recurrent nosebleeding severe enough that it leads to clinical depression, anxiety, or post-traumatic stress disorder,” Al-Samkari says.
Bleeding isn’t limited to the nose, however. Telangiectasias in the stomach or intestines occur in around 80% of patients, and roughly a third will develop chronic gastrointestinal (GI) bleeding, usually after age 30.
Over time, repeated bleeding from the nose and GI tract can lead to iron-deficiency anemia, which occurs in approximately 60% to 70% of patients and is often recurrent. The National Bleeding Disorders Foundation’s Medical and Scientific Advisory Council (MASAC) recommends that all people with HHT be routinely screened for iron-deficiency anemia, regardless of sex, age, or severity of symptoms. Notably, the guidelines set higher thresholds than standard lab reference ranges, recognizing that chronic blood loss in HHT puts patients at risk even when standard tests might appear normal.
Treatment options for iron-deficiency anemia range from diet and oral iron supplements to IV iron infusions or red blood cell transfusions, depending on severity. Al-Samkari says it’s not uncommon for patients with HHT to rely on regular intravenous iron infusions.
Diagnosis, Screening, and Why Early Detection Matters
Because HHT can mimic many other conditions, getting the correct diagnosis is a critical first step. Evaluation typically includes:
- A detailed personal and family history, especially focusing on nosebleeds and unexplained anemia.
- A focused physical exam looking for telangiectasias on the skin, lips, tongue, and inside the nose.
- Review of established HHT clinical criteria and guidelines.
- Consideration of DNA-based genetic testing and genetic counseling.
- Targeted imaging to screen for AVMs in the lungs, brain, liver, and other organs.
Genetic testing can identify mutations in genes in the majority of patients, but a negative genetic test does not fully rule out HHT. That’s why clinical evaluation and family history remain essential.
Early detection is key because most major manifestations of HHT are treatable once identified. Nosebleeds can often be controlled with stepwise therapies — from humidification and topical treatments to tranexamic acid, laser procedures, and, in severe cases, surgical options. “Thankfully, nosebleeding and gastrointestinal bleeding in HHT is now manageable with advanced medications that reduce abnormal blood vessel growth — so-called antiangiogenic medications that have been repurposed from the treatment of cancer. These include medications such as bevacizumab, pomalidomide and pazopanib,” Al-Samkari says. AVMs in the lungs and brain often can be treated with embolization, surgery, or other targeted therapies before they cause life-threatening complications.
“HHT remains without FDA-approved therapies, but this will hopefully change soon, given that new drug development has recently accelerated drastically in this disease,” Al-Samkari says. At least six new medications developed specifically to treat HHT that target bleeding and blood vessel formation are now in clinical trials or set to enter clinical trials over the next six months.
“The future is therefore looking brighter for the 80,000 Americans and 1.6 million people worldwide with HHT,” Al-Samkari says.