What is Hereditary Hemorrhagic Telangiectasia (HHT)?

In the normal circulatory system, arteries take oxygenated blood from the heart and push it out to all parts of the body under high pressure, while the veins return the blood back to the heart. Small capillaries typically connect the arteries to the veins. A person with HHT lacks capillaries in a few blood vessels in critical locations resulting in arteries that connect directly into veins, creating a fragile vessel that can bleed or cause other problems. These abnormal blood vessels are called telangiectases (tel-AN-jee-eck-TA-sees) if they involve small blood vessels (nose, stomach and intestine) and arteriovenous malformations (AVMs) if they involve a larger blood vessel (lung, brain and liver). Telangiectases often occur near the surface of the skin like the mucous membranes in the nose while AVMs appear in the internal organs of the body.

Most patients with HHT are aware of their nosebleeds yet are often unaware of the high frequency (over 40 percent) of brain or lung involvement and that AVMs in these areas that may lead to severe complications if untreated. Further, these AVMs are more often than not without symptoms, and physicians treating complications often don't realize that the underlying disorder is HHT. As a result, many patients are undiagnosed.

What are the symptoms of Hereditary Hemorrhagic Telangiectasia (HHT)?

The location of the telangiectases or AVMs impacts what problems a person with HHT might develop. The most common symptom by far is nosebleeds, affecting about 90 percent of HHT patients. Those with abnormal GI tract blood vessels should watch for dark stools or blood in the stool. Nosebleeds and bleeding into the intestine can cause severe anemia resulting in fatigue, shortness of breath, chest pain and light-headedness. Those with AVMs in the lung (called pulmonary AVMs or PAVMs) may be short of breath at rest or with exercise, may develop stroke or mini-stroke (TIA), heart attack or unusual infection such as brain abscess. Rarely, PAVMs can rupture and cause bleeding in the chest (especially during pregnancy) or coughing up blood. HHT patients with brain AVMs (also called cerebral AVMs or CAVMs) do not generally have warning symptoms prior to a life-threatening brain hemorrhage. Heart failure is another risk HHT patients face due to high flow liver AVMs (also called hepatic AVMs or HAVMs); these patients can also develop liver or bile duct problems.

How does HHT affect women and pregnancy?

Female hormones are known to affect bleeding of abnormal HHT blood vessels. For some women, nosebleeds vary through the menstrual cycle and become worse after menopause. Most pregnant women with HHT can expect no serious HHT-related complications, although they will generally be classified as high-risk. For some, new skin telangiectases are detected, while others report improvements. There is great concern for pregnant women with an AVM in their lung. During pregnancy, there is a 60 percent increase in blood circulation that is essential to the development of the baby. This increase in pressure on weak abnormal blood vessels increases the risk of a life threatening rupture in the lung. Research shows that it is safe and effective to perform treatment (embolization — see below) on pulmonary AVMs during the second trimester of pregnancy.

How is HHT diagnosed?

In the mid 1990s scientists discovered that an abnormal gene on either chromosome 9 or 12 causes HHT. Chromosome 9 (endoglin, HHT-1) and chromosome 12 (activin-like kinase, HHT-2) tell the body to produce a substance that is involved in the formation of blood vessels. There are at least three other abnormal genes that can cause HHT. HHT is a "dominant" disorder since one abnormal copy of the gene from one parent can cause the disorder. Although there is a 50 percent chance of inheriting this abnormal gene, children who do not have it cannot pass on the disease.

Genetic testing for HHT is available at HHT Centers of Excellence, including Penn. Genetic testing can be extremely helpful in screening large families, in particular family members who have no signs or symptoms of HHT. The diagnosis can be made clinically if a person has three or more of the following criteria and HHT is suspected if they have two of the criteria:

  1. Nosebleeds that are spontaneous and recurrent
  2. Telangiectases are prevalent at characteristic sites, such as lips, oral cavity, fingers and nose
  3. AVMs are present in lung, brain, GI, liver or spine
  4. Family history indicates that a parent, sibling or child has HHT

How is HHT treated at the University of Pennsylvania?

Interventional Radiologists are one of the few specialists who can permanently treat this disease that affects approximately half a million people worldwide. As vascular experts, Interventional Radiologists perform embolization - blocking the blood flow to the affected area - to prevent symptoms and complications.

The University of Pennsylvania Hereditary Hemorrhagic Telangiectasia (HHT) Center of Excellence is co-directed by Drs. Scott Trerotola and Reed Pyeritz, and is a multidisciplinary practice which facilitates the comprehensive coordination of care necessary for treating HHT patients, including the full array of counseling, screening, diagnosis, and treatment.

What is a pulmonary arteriovenous malformation (PAVM)?

A PAVM is an abnormal connection between one or more arteries in the lung with one or more veins (see figures). In a normal lung, the capillary is not only the site where oxygen enters the bloodstream, it is also a filter for small blood clots and bacteria that occur in our bloodstream all the time. In a PAVM, this filtering function is lost, and thus a clot or bacterium can pass through to the pulmonary veins and from there to the heart, where it is pumped anywhere in the body. Depending upon where it goes, it can produce a variety of symptoms listed above, most commonly stroke. In a simple PAVM there is one feeding artery, and in a complex PAVM there are two or more. A more rare form of PAVM called diffuse type has innumerable abnormal connections.

How are PAVMs treated?

The standard treatment for PAVMs is a minimally invasive, image-guided procedure called embolization, which is performed by Interventional Radiologists at HHT Centers of Excellence and performed by Dr. Trerotola at Penn. In this procedure, the abnormal connection between the artery and vein is blocked with a variety of devices, most commonly a basket-like device called an Amplatzer Vascular Occluder in conjunction with platinum coils. As shown in the figures, these devices cause the feeding artery to clot and become a scar, and the abnormal connection shrinks away over time.

The embolization procedure is done on an outpatient basis under moderate sedation and local anesthesia. Depending upon the number of PAVMs, the procedure can take 1-4 hours and the recovery is two hours. Patients can return to normal activities the next day.

How successful is PAVM embolization?

In experienced hands such as in an HHT Center of Excellence, PAVM embolization is virtually 100 percent successful. Depending upon the type of embolization device used, there is up to a 20 percent chance that the treated PAVM will need further treatment in the future. However, based on research done at Penn, if the combination of an Amplatzer and coils is used, this risk is far lower, approaching 0 percent.

Can PAVMs recur?

As noted above, provided combination therapy can be used, the risk of a treated PAVM needing to be retreated is low. However, PAVMs treated in other fashions may persist or recur and these can be retreated. Also, PAVMs too small to treat initially may grow over time, which is why lifelong surveillance with CT scans every five years is necessary.

Selected publications about PAVMs from the Penn HHT center

Woodward CS, Pyeritz RE, Chittams JL, Trerotola SO, Treated Pulmonary Arteriovenous Malformations: Patterns of Persistence and Associated Retreatment Success. Radiology. 2013;269:919-926

Trerotola SO and Pyeritz RE. PAVM embolization: an update. AJR 2010;195:837-45.

Trerotola SO and Pyeritz RE. Does use of coils in addition to Amplatzer vascular plugs prevent recanalization? AJR 2010; 195:766-771.

Trerotola SO, Bernhardt B, Pyeritz R, Outpatient single-session pulmonary arteriovenous malformation embolization. JVIR 2009;20:1287-1291.

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