When is short-term vs long-term prophylaxis therapy given in patients with hereditary angioedema (HAE)?

Short-Term vs Long-Term Prophylaxis in Hereditary Angioedema

Short-term prophylaxis should be used for patients undergoing procedures or experiencing predictable triggers, while long-term prophylaxis is indicated for patients with frequent, severe attacks that significantly impact quality of life. 1

Short-Term Prophylaxis (STP)

Short-term prophylaxis is indicated in the following situations:

• Predictable upcoming stressors that are known to precipitate HAE attacks, such as:

  • Dental procedures, particularly extractions 1
  • Invasive medical or surgical procedures 1
  • Procedures involving the head and neck region, especially those requiring intubation 1

• Medication options for STP include:

  • C1 inhibitor replacement therapy (first-line): 1000-2000 U or 20 U/kg for children, administered several hours before the procedure 1
  • Attenuated androgens (second-line): Danazol 6-10 mg/kg/day in divided doses (maximum 200 mg three times daily) for 5-10 days before and 2 days after the procedure 1, 2
  • Fresh frozen plasma (FFP): 2 units (10 mL/kg for children) administered 12 hours before the procedure, when first-line therapies are unavailable 1
  • Tranexamic acid: 30-50 mg/kg/day (maximum 3-4.5 g daily) in 2-3 divided doses, from 5 days before until 2 days after the procedure, though efficacy is questionable 1

• Timing of administration:

  • STP should be administered before the procedure to prevent attacks 1, 3
  • For emergency procedures, plasma-derived C1INH is preferred 1

Long-Term Prophylaxis (LTP)

Long-term prophylaxis should be individualized based on:

• Attack frequency and severity 1

• Location of attacks (especially laryngeal involvement) 1

• Access to acute care 1

• Comorbid conditions 1

• Patient preference 1

• Medication options for LTP include:

  • C1 inhibitor replacement therapy (first-line): Plasma-derived C1INH at a starting dose of 1000 U every 3-4 days, with dose adjustments based on response 1
  • Attenuated androgens: Danazol at the lowest effective dose (typically 100 mg every other day to 600 mg daily) 1, 2
  • Antifibrinolytic agents: Tranexamic acid 30-50 mg/kg/day in 2-3 divided doses (maximum 3 g/day) 1

Special Considerations

Children

• For STP: FFP (10 mL/kg) for acute treatment and tranexamic acid (15-25 mg/kg 2-3 times daily) are preferred when first-line therapies are unavailable 1
• For LTP: Tranexamic acid is preferred over androgens due to concerns about growth and development 1
• Attenuated androgens should generally be avoided before Tanner Stage V of puberty 1

Pregnancy

• C1INH is the only recommended treatment for both acute attacks and prophylaxis during pregnancy 1
• Androgens are contraindicated during pregnancy 1

Monitoring and Adjustments

• For androgen therapy: Regular monitoring for side effects with blood tests and periodic hepatic ultrasounds 1
• Dose adjustments:
  • For LTP with androgens, start with either high or low dose and titrate to the lowest effective dose 1
  • Changes in dosage should not occur more frequently than once per week 1

Common Pitfalls to Avoid

• Delaying treatment of acute attacks, which leads to longer attack duration and increased morbidity 3
• Using inappropriate treatments such as standard angioedema treatments, which are ineffective for HAE 3
• Failing to have on-demand therapy available during procedures, even when STP is administered 1
• Overlooking the need for airway monitoring during oropharyngeal or laryngeal attacks 1
• Not considering newer therapies that may provide better disease control with fewer side effects 4

By following these guidelines, clinicians can effectively manage HAE patients with appropriate prophylaxis strategies to minimize morbidity and mortality while improving quality of life.