What is the management plan for a patient with hereditary angioedema (HAE)?

Management of Hereditary Angioedema (HAE)

The management of hereditary angioedema requires a comprehensive approach including on-demand treatment for acute attacks, short-term prophylaxis for procedures, and long-term prophylaxis for frequent attacks, with plasma-derived C1 inhibitor (pdhC1INH) being the first-line therapy for acute attacks. 1

Acute Attack Management

First-Line Treatments

• Plasma-derived C1 inhibitor concentrate (1000-2000 U intravenously) is the most effective first-line treatment for acute HAE attacks 1, 2
• Other effective first-line options include icatibant (30 mg subcutaneously) and ecallantide (plasma kallikrein inhibitor) 2, 3
• Early treatment is critical - on-demand treatment is most effective when administered as early as possible during an attack 1, 3
• All patients with HAE should have access to an effective on-demand HAE-specific agent and a contingency plan for management of acute attacks 1

Airway Management for Laryngeal Attacks

• Laryngeal attacks should be observed in a medical facility capable of performing intubation or tracheostomy if necessary 1, 4
• Patients should be closely monitored for signs of impending airway closure (change in voice, loss of ability to swallow, difficulty breathing) 1, 4
• Avoid direct visualization of the airway unless absolutely necessary, as trauma from the procedure can worsen angioedema 1
• If signs of impending airway closure develop, consider elective intubation by physicians highly skilled in airway management 1, 4

Ineffective Treatments for Acute Attacks

• Standard angioedema treatments (epinephrine, corticosteroids, antihistamines) are NOT effective for HAE attacks 4, 2
• Neither anabolic androgens nor antifibrinolytic drugs provide reliably effective treatment for acute attacks 1
• These medications require several days to become effective and thus have minimal impact during the acute phase 1

Supportive Care

• For abdominal attacks, provide symptomatic treatment including analgesics, antiemetics, and aggressive hydration 1, 2
• Monitor for narcotic addiction risk in patients with frequent attacks 1
• Fresh frozen plasma (FFP) may be used if specific HAE medications are unavailable, though it carries theoretical risk of worsening symptoms 1

Prophylactic Treatment

Short-Term Prophylaxis

• Short-term prophylaxis is indicated before dental work, surgical procedures, or invasive medical procedures 1
• First-line option: plasma-derived C1INH (1000-2000 U or 20 U/kg for children) 1, 2
• Alternative options:
  • Fresh frozen plasma (2 U or 10 mL/kg for children) administered several hours before procedure 1
  • High-dose anabolic androgens (danazol 6-10 mg/kg/day in divided doses, maximum 200 mg three times daily) for 5-10 days before and 2 days after procedure 1, 5
• For emergency procedures and in pregnant patients, plasma-derived C1INH is preferred 1

Long-Term Prophylaxis

• Consider for patients with frequent or severe attacks 2, 3
• First-line options:
  • Plasma-derived C1INH (intravenous or subcutaneous) 1, 2
  • Lanadelumab (monoclonal antibody) 1, 3
• Second-line options:
  • Attenuated androgens (danazol, stanozolol, oxandrolone) at lowest effective dose 1, 6
  • Antifibrinolytic agents (tranexamic acid) 1, 6
• Anabolic androgens should be initiated at either high or low dose and then slowly titrated to the lowest effective dose 1
• Dosage adjustments should not be made more frequently than once per week 1

Special Considerations

Pregnancy

• pdhC1INH is recommended as first-line therapy for both acute attacks and prophylaxis during pregnancy 1
• Antifibrinolytics may be used for mild attacks during pregnancy if pdhC1INH is unavailable 1
• Anabolic androgens should be discontinued at least 2 months before attempting conception due to risk of fetal abnormalities 1
• Close follow-up by staff familiar with HAE is recommended for at least 72 hours after delivery 1

Home Therapy and Self-Administration

• Self-administration of medication should be encouraged when appropriate 2, 3
• Home therapy significantly reduces time to treatment and improves outcomes 2, 7
• Patient education about recognizing attacks and proper administration technique is essential 8, 7

Common Pitfalls to Avoid

• Delaying treatment of acute attacks, especially those involving the airway 1, 4
• Using standard angioedema treatments (antihistamines, corticosteroids, epinephrine) which are ineffective for HAE 4, 2
• Discharging patients with oropharyngeal or laryngeal involvement without adequate observation 1
• Failing to provide patients with access to on-demand treatment 1, 8
• Inappropriate use of narcotics leading to addiction risk in patients with frequent attacks 1

Global Access Considerations

• Significant disparities exist in HAE management resources between high-income and low-income countries 1
• In many low-income countries, first-line treatments are unavailable, and patients rely on second-line options like attenuated androgens and antifibrinolytics 1
• Efforts should be made to improve global access to effective HAE treatments 1