Hereditary haemorrhagic telangiectasia is a genetic condition that causes abnormal blood vessels throughout the body, leading to frequent bleeding and potential complications in multiple organs. Treatment focuses on managing symptoms, preventing serious complications, and improving quality of life through a combination of established therapies and emerging approaches being tested in clinical research.

Managing a Complex Vascular Condition

When someone receives a diagnosis of hereditary haemorrhagic telangiectasia, often called HHT or Osler-Weber-Rendu syndrome, they typically face a lifetime of managing bleeding episodes and monitoring for complications. The main goals of treatment are to control bleeding, prevent dangerous events such as strokes or brain bleeds, manage anaemia that results from blood loss, and help patients maintain a good quality of life despite their symptoms. Treatment decisions depend heavily on which organs are affected, how severe the symptoms are, and the individual characteristics of each patient^[1].

Because HHT affects blood vessels in different parts of the body in different ways, treatment must be highly personalised. Some people experience mainly nosebleeds and skin changes, while others develop large abnormal blood vessel connections called arteriovenous malformations or AVMs in their lungs, brain, or liver. These larger malformations can cause life-threatening complications if they rupture or create problems with blood flow^[3]. The severity of HHT varies dramatically even within the same family, which means that treatment plans need to be tailored to each person’s specific situation.

Medical societies have developed guidelines to help doctors screen for complications and recommend treatments. These guidelines emphasise the importance of early diagnosis and regular monitoring at specialised centres familiar with HHT. Patients benefit from coordinated care involving multiple specialists, including ear, nose and throat doctors, blood specialists, lung doctors, brain specialists, and others depending on which organs are affected^[3].

Alongside the established treatments that doctors use routinely, researchers are actively investigating new therapies through clinical trials. These studies explore drugs that target the biological pathways disrupted in HHT, offering hope for more effective treatments in the future. Some of these experimental approaches have shown promising early results, though they require further testing before becoming standard care.

Standard Medical and Surgical Approaches

The foundation of HHT treatment involves addressing the most common and troublesome symptom: recurrent nosebleeds. These bleeds, medically termed epistaxis, occur because fragile abnormal blood vessels in the nose lining rupture easily. More than ninety percent of people with HHT experience nosebleeds, which often begin in childhood or adolescence and typically worsen with age^[8].

For managing nosebleeds at home, doctors recommend keeping the nasal passages moist with humidification, applying topical moisturising therapies such as nasal gels or ointments, and learning proper techniques to stop active bleeding. When a nosebleed starts, patients should sit upright, lean slightly forward, and apply firm pressure to the soft part of the nose for at least ten minutes. Lying down or tilting the head back can cause blood to flow down the throat, which may lead to nausea^[3].

Medical treatments for more severe or frequent nosebleeds include drugs that help blood clot more effectively. Antifibrinolytic agents such as tranexamic acid work by preventing the breakdown of blood clots that form after bleeding. This medication can be taken orally on a regular basis or used topically in the nose^[9].

When nosebleeds become severe enough to require surgical intervention, ear, nose and throat specialists can perform procedures to seal or remove the problematic blood vessels. Endonasal coagulation, using laser or electrical energy to carefully burn and close abnormal vessels, is often considered a first-line surgical option. This procedure can provide relief for many patients, though the effects tend to be temporary as new abnormal vessels develop over time^[8].

The chronic blood loss from nosebleeds and bleeding in the digestive tract frequently causes iron deficiency anaemia, a condition where the blood cannot carry enough oxygen because of low iron levels. Treating this anaemia is crucial for maintaining energy and overall health. Doctors prescribe iron supplements, often given intravenously through a vein when oral iron tablets are not absorbed well enough or cannot keep up with ongoing blood loss. In cases of severe anaemia, blood transfusions may be necessary to quickly restore healthy red blood cell levels^[3].

For abnormal blood vessels on the skin or in the nose lining, doctors may use laser treatments. Vascular laser therapy or intense pulsed light treatment directs concentrated light energy at the visible blood vessels, causing them to shrink and close. The heat destroys the abnormal vessels while leaving minimal scarring. Multiple treatment sessions are typically needed, and ongoing maintenance treatments may be required as new vessels form^[6].

Arteriovenous malformations in internal organs require more complex interventions. Pulmonary AVMs in the lungs, which affect approximately fifteen to thirty percent of HHT patients, are usually treated even when not causing symptoms because they pose significant risks. The preferred treatment is embolisation, a minimally invasive procedure where a specialist threads a thin tube through blood vessels to reach the AVM and blocks it with tiny plugs or coils. This prevents blood from flowing through the abnormal connection^[8].

Brain AVMs present particularly serious risks of bleeding or stroke. When discovered, they may be treated through surgery, embolisation, or stereotactic radiosurgery, which uses focused radiation beams to gradually close off the malformation. The choice of treatment depends on the size, location, and characteristics of the brain AVM. Some small, asymptomatic brain AVMs may simply be monitored without immediate intervention^[3].

Liver involvement in HHT can lead to high-output heart failure, where the heart must work excessively hard to pump blood through the numerous abnormal connections in the liver. When liver AVMs cause symptoms, medical management focuses on treating heart failure and its complications. In severe cases that do not respond to medication, liver transplantation may be considered as a treatment option^[3].

Patients with HHT require ongoing surveillance throughout their lives. Annual blood tests check for anaemia by measuring haemoglobin and iron levels. Screening for lung AVMs is recommended every five years in adults using specialised echocardiography with contrast bubbles. Brain MRI screening helps detect occult brain AVMs in approximately ten percent of patients. Regular monitoring allows doctors to detect and treat complications before they become dangerous^[8].

Emerging Therapies in Clinical Research

Understanding that HHT results from mutations in genes that control blood vessel formation has opened doors to developing targeted therapies. Researchers have identified that mutations in genes such as ENG, ACVRL1, and SMAD4 prevent the production of proteins normally found in blood vessel linings, leading to the development of abnormal vessels. This knowledge has guided scientists toward drugs that might correct these underlying biological problems^[2].

One of the most promising approaches currently being studied involves blocking vascular endothelial growth factor, or VEGF, a protein that promotes blood vessel growth. People with HHT have elevated levels of VEGF, which may contribute to the formation of abnormal vessels. A drug called bevacizumab, which is an antibody that binds to and neutralises VEGF, has been tested in HHT patients with encouraging results^[13].

Bevacizumab was originally developed and approved for treating certain cancers, but doctors have begun using it in HHT patients who suffer from severe bleeding that has not responded to other treatments. The drug is administered as an intravenous infusion, typically given every two weeks for several months. Clinical studies have shown that bevacizumab can reduce the frequency and severity of nosebleeds, decrease the need for blood transfusions, and improve quality of life in some patients^[14].

In one reported case, a man in his forties with HHT who required three to five units of blood transfusion monthly because of gastrointestinal bleeding was treated with bevacizumab at a dose of five milligrams per kilogram every two weeks for twelve weeks. Within the first month of treatment, his symptoms improved markedly, and he did not require any blood transfusions during the entire three-month treatment period. The patient experienced no adverse side effects from the medication^[14].

Some researchers have also investigated using bevacizumab applied directly into the nose in a nasal spray form. This intranasal bevacizumab approach aims to treat the abnormal blood vessels in the nose lining while minimising exposure of the rest of the body to the drug. Early reports suggest this may be effective for reducing nosebleeds, but more rigorous research is needed to determine optimal dosing, long-term effectiveness, and safety^[10].

Beyond anti-VEGF therapies, scientists are exploring other molecular pathways that might be targeted to prevent or treat HHT. High-throughput screening studies have identified several compounds that could potentially correct the blood vessel defects caused by HHT gene mutations. These include drugs that affect proteins such as FKBP12, PI3-kinase, and angiopoietin-2, all of which play roles in blood vessel development and stability^[13].

Researchers are also investigating hormone-based therapies. Some studies have examined the use of drugs that block oestrogen effects or alter hormone levels, based on observations that symptoms sometimes worsen during pregnancy when hormone levels change dramatically. Anti-oestrogen therapy has shown some promising results in reducing bleeding, though further research is needed to understand the long-term effects and limitations of lifelong hormone treatment^[10].

The location and design of clinical trials for HHT treatments vary. Some studies are conducted at specialised HHT centres of excellence in North America, Europe, and other regions around the world. These centres have the expertise and resources to carefully evaluate new treatments in this relatively rare condition. Eligibility for clinical trials typically depends on factors such as the severity of symptoms, which organs are affected, whether standard treatments have been tried, and the patient’s overall health status^[7].

Clinical trials generally progress through distinct phases. Phase I trials primarily assess safety and determine appropriate dosing in small numbers of patients. Phase II trials expand to larger groups to evaluate whether the treatment shows evidence of effectiveness while continuing to monitor safety. Phase III trials compare the new treatment against current standard treatments in large patient populations to definitively establish benefits and risks. Most experimental HHT treatments are currently in early phases of testing.

Gene therapy approaches, which would aim to correct the underlying genetic defects in HHT, are being explored in laboratory studies but have not yet reached human testing. These futuristic treatments would theoretically address the root cause of the disease rather than just managing symptoms. However, delivering corrected genes specifically to blood vessel cells throughout the body presents significant technical challenges that researchers are working to overcome^[13].

Most common treatment methods

• Topical nasal care and humidification
  • Moisturising gels or ointments applied to nasal passages to prevent drying and cracking
  • Humidifiers to maintain moisture in the air and reduce nasal irritation
  • Saline nasal sprays to keep tissues moist
• Iron replacement therapy
  • Oral iron supplements taken daily to replace iron lost through bleeding
  • Intravenous iron infusions when oral supplements are insufficient or poorly tolerated
  • Regular monitoring of iron levels, haemoglobin, and haematocrit
• Antifibrinolytic medications
  • Tranexamic acid taken orally or applied topically to prevent clot breakdown
  • Used to reduce frequency and severity of bleeding episodes
• Blood transfusions
  • Administered when anaemia becomes severe despite iron replacement
  • May be required regularly in patients with persistent heavy bleeding
• Laser and ablation therapies
  • Vascular laser treatment for skin telangiectases
  • Intense pulsed light therapy for visible blood vessels
  • Endonasal coagulation using laser or electrical energy to seal nasal blood vessels
  • Cauterisation of bleeding sites during active episodes
• Embolisation procedures
  • Catheter-based technique to block pulmonary arteriovenous malformations
  • Tiny plugs or coils inserted to prevent blood flow through abnormal vessels
  • Used for lung, liver, and some other internal AVMs
  • Minimally invasive alternative to open surgery
• Surgical interventions
  • Nasal septum skin grafting for severe recurrent nosebleeds
  • Surgical removal of accessible arteriovenous malformations
  • Neurosurgery for brain AVMs when indicated
  • Liver transplantation in cases of severe symptomatic liver involvement
• Stereotactic radiosurgery
  • Focused radiation beams to gradually close brain arteriovenous malformations
  • Non-invasive alternative to surgical removal in selected cases
• Anti-angiogenic therapy (experimental)
  • Bevacizumab infusions to block vascular endothelial growth factor
  • Used for severe bleeding not responsive to standard treatments
  • Intranasal bevacizumab spray being studied for nosebleeds
  • Currently considered off-label use requiring further research
• Antibiotic prophylaxis
  • Preventive antibiotics before dental work and certain medical procedures
  • Required for patients with pulmonary AVMs to prevent brain infections and strokes