Hereditary Hemorrhagic Telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a genetic disorder affecting how blood vessels develop throughout the body. This condition is inherited in an autosomal dominant pattern, meaning a child has a 50% chance of inheriting the altered gene. While HHT is a chronic condition often characterized by recurrent nosebleeds and small lesions called telangiectasias, the potential for specific internal complications makes it potentially life-threatening. The severity of HHT depends on the development of abnormal blood vessel connections in vital organs, which often present without prior symptoms. Early identification and treatment of these internal abnormalities are the primary focus for preventing serious events.
The Core Risk: Understanding Arteriovenous Malformations (AVMs)
The underlying problem in HHT is the failure of small blood vessels, called capillaries, to fully form in certain areas. Capillaries normally connect arteries, which carry high-pressure blood, to veins, which return low-pressure blood. In people with HHT, this capillary network is bypassed, leading to a direct connection between an artery and a vein. This abnormal vessel structure is known as an arteriovenous malformation (AVM) when it involves larger vessels. Since arterial blood is under high pressure, the fragile walls of the AVM are constantly stressed. This structural weakness can lead to two main life-threatening issues: rupture, causing internal bleeding, or high-flow shunting, which causes complications by overwhelming the circulatory system.
Organ-Specific Life-Threatening Complications
The most dangerous complications of HHT involve AVMs that develop in the lungs and the brain. Pulmonary AVMs (PAVMs) are present in 15% to 45% of HHT patients and pose a significant risk of stroke. These malformations allow blood to bypass the capillaries that normally filter out microscopic clots, bacteria, and air bubbles, letting them travel directly to the brain. This process, called paradoxical embolism, can result in a stroke or a brain abscess (infection).
Cerebral AVMs (CAVMs) in the brain affect about 10% to 20% of patients, but their consequences are often severe. The fragile nature of the malformation wall means that a rupture can cause an intracranial hemorrhage, a type of bleeding stroke that can be immediately fatal or cause permanent neurological damage. CAVMs may also present with symptoms such as seizures or chronic headaches.
AVMs can also form in the liver, occurring in up to 75% of HHT patients, though rupture is rare in this location. Liver AVMs are characterized by massive blood shunting, where a large volume of blood flows quickly from the arteries to the veins. This high-volume circulation can strain the heart, leading to high-output cardiac failure, where the heart cannot pump blood fast enough to meet the body’s needs.
A less frequent, but still serious, complication involves AVMs in the spinal cord. These spinal AVMs can cause pressure on the nerves and surrounding tissues. If they rupture or cause significant structural damage, the resulting complications can include paralysis.
Screening and Diagnosis for High-Risk AVMs
Since the most dangerous AVMs are often asymptomatic until a catastrophic event occurs, proactive screening is the cornerstone of HHT management. The diagnosis of HHT itself is made using clinical criteria. Once a diagnosis is confirmed, or even if the condition is suspected, screening for internal AVMs is immediately necessary.
- Recurrent nosebleeds
- Visible telangiectasias
- Internal AVMs
- A family history of the disorder
Screening for PAVMs often begins with a non-invasive test called transthoracic contrast echocardiography, or a “bubble test.” This procedure uses agitated saline contrast injected into a vein; if bubbles appear in the left side of the heart, it indicates a right-to-left shunt, strongly suggesting a PAVM. If this test is positive, a CT scan is used to precisely locate and measure the PAVM.
To screen for CAVMs, a specialized magnetic resonance imaging (MRI) of the brain is performed. This imaging technique identifies malformations that are at high risk of bleeding. Family screening is also important, as first-degree relatives should be evaluated and screened for visceral AVMs even if they have no symptoms.
Therapeutic Management of HHT Risks
The primary goal of therapy is to eliminate or significantly reduce the risk posed by high-flow AVMs in the lungs and brain. The most common and effective treatment for PAVMs, and many CAVMs, is transcatheter embolization. This minimally invasive procedure involves guiding a catheter through a blood vessel to the site of the AVM. Once at the site, a blocking agent, such as a coil or a specialized plug, is deployed to occlude the feeding artery, which shuts down the blood flow to the malformation.
Embolization is generally recommended for any PAVM with a feeding vessel greater than 2-3 millimeters in diameter to prevent stroke. For certain brain AVMs where embolization is not feasible, surgical intervention or focused radiation therapy may be considered to remove or shrink the lesion.
Newer systemic drug therapies, such as anti-angiogenic agents, are also being used to manage the severity of some AVMs, particularly those in the liver and gastrointestinal tract. These medications work by targeting the abnormal signaling pathways that cause the vessels to form and grow. With consistent screening and timely intervention, the life-threatening complications associated with AVMs can be significantly mitigated, allowing most individuals with HHT to live a normal lifespan.