What is the management approach for patients with Hereditary Hemorrhagic Telangiectasia (HHT)?

Management of Hereditary Hemorrhagic Telangiectasia (HHT)

Patients with Hereditary Hemorrhagic Telangiectasia should be managed by a multidisciplinary team at specialized HHT centers of excellence to optimize outcomes and reduce complications. 1

Diagnosis and Screening

• Diagnosis is based on the Curaçao criteria, which includes:

  • Recurrent spontaneous epistaxis
  • Multiple telangiectasias
  • Visceral lesions (AVMs in lungs, liver, brain, GI tract)
  • First-degree relative with HHT 2

• Genetic testing is recommended for:

  • Asymptomatic family members from families with known HHT
  • Diagnostic confirmation in suspected cases
  • Identification of specific mutations (ENG, ACVRL1/ALK1, SMAD4) 2

Organ-Specific Screening and Management

Liver Involvement

• Screening: Doppler ultrasound is recommended as the initial screening technique for liver vascular malformations due to its accuracy, non-invasiveness, availability, and low cost 2

• Management approach:

  • Asymptomatic liver involvement: No treatment is currently recommended 2
  • Symptomatic liver involvement:
    • High-output heart failure: Intensive medical therapy (correction of anemia, salt restriction, diuretics, antihypertensive agents) 2
    • Portal hypertension complications: Treat as in cirrhotic patients 2
    • Cholangitis: Antibiotics (biliary stenting not recommended) 2

• For patients with progressive deterioration despite medical therapy:

  • Liver transplantation is the only definitive curative option for severe hepatic vascular malformations 2
  • Transarterial embolization should be absolutely avoided in patients with biliary symptoms due to high risk of complications 1

Pulmonary AVMs

• All HHT patients should undergo screening for pulmonary AVMs due to risk of serious CNS complications (stroke, brain abscess) 3
• Treatment is recommended for feeding arteries ≥3 mm to prevent paradoxical embolism 2
• Percutaneous embolization is the preferred treatment approach 3

Epistaxis and GI Bleeding Management

• First-line treatments for epistaxis:

  • Humidification, nasal moisturization, and avoidance of trauma
  • Topical therapies (saline sprays, lubricants)
  • Antifibrinolytics (tranexamic acid) for moderate-severe cases 2

• For refractory GI bleeding and epistaxis:

  • Systemic antiangiogenic therapy with bevacizumab has shown promising results 2
  • Both scheduled "continuous" maintenance and as-needed "intermittent" maintenance strategies are used 2

Anemia and Iron Deficiency

• Screen all adults with HHT for iron deficiency regardless of bleeding symptoms 2
• Screen children with recurrent bleeding and/or anemia symptoms 2
• Treatment approach:
  • Oral iron as initial therapy for mild deficiency
  • Intravenous iron as first-line for severe anemia or when oral replacement is expected to be inadequate 2
  • Red blood cell transfusions for symptomatic anemia or hemoglobin <7 g/dL 2

Special Considerations

Anticoagulation and Antiplatelet Therapy

• Avoid dual antiplatelet therapy and combination of antiplatelet with anticoagulation when possible 2
• When anticoagulation is necessary:
  • Heparin agents and vitamin K antagonists are preferred over direct oral anticoagulants 2
  • Consider hemostatic treatments or anticoagulation modification in poorly tolerating patients 2

Pregnancy Management

• Specialized obstetric care is recommended due to potential complications 1
• Screening for pulmonary AVMs before pregnancy is advisable to prevent complications 2
• Avoid transarterial embolization during pregnancy if possible 2

Pitfalls and Caveats

1. Diagnostic delays are common in HHT, leading to preventable complications. Early referral to specialized centers is crucial 1

2. Fragmented care is detrimental - coordinated multidisciplinary management at HHT centers provides optimal outcomes 1

3. Inappropriate interventions can cause harm:

   • Transarterial embolization in patients with biliary symptoms can lead to catastrophic complications 1
   • Transjugular intrahepatic portosystemic shunts may worsen hyperdynamic circulation in HHT patients with liver involvement 2

4. Hormonal therapies (estrogens, progestins, SERMs) have inconsistent benefits and significant thromboembolic risks 2

5. Antiangiogenic therapies require careful monitoring for thrombotic risks and optimal maintenance strategies are still being determined 2