Clinical Management of HAE
Clinical management of
hereditary angioedema (HAE) is complex and includes avoiding potential
triggers, management of acute attacks, and prophylaxis.12
Acute and prophylactic needs of patients
Treatment of HAE is complex, because it can involve the use of separate algorithms:
- Treatment of acute HAE attacks.
- Prophylaxis, which includes preparation for exposure to known triggers, such as
dental procedures, surgeries, or giving birth, and treatment for patients with life-threatening,
Unlike in Canada and Europe, there were no specific treatments in the United States
for acute attacks of HAE prior to 2009. However, there are now 3 treatment options:
- Complement-1 esterase inhibitor protein
(C1-INH) concentrate for acute HAE attacks in adults and adolescents.12
kallikrein inhibitor for acute HAE attacks in individuals 12 years of age
- Bradykinin B2 Receptor Antagonist for treatment of acute HAE attacks in adults 18
years or older.
C1-INH therapy works by replacing the missing or malfunctioning C1-INH protein in
patients with a C1-INH deficiency. Adverse reactions linked to C1-INH therapy include nausea, diarrhea, abdominal pain, dysguesia, and muscle spasms.
A kallikrein inhibitor works by blocking the generation of kallikrein and its byproduct,
bradykinin, which is thought to cause HAE attacks. The therapy is generally
well-tolerated, but there have been reports of anaphylaxis associated with the administration
of this therapy.
Bradykinin B2 Receptor Antagonist
Bradykinin is a vasodilator thought to be responsible for the characteristic HAE
symptoms of localized swelling, inflammation, and pain. Bradykinin B2 receptor antagonists
bind to the bradykinin B2 receptor and prevent bradykin from activating this receptor.
This blocks bradykin from inducing the clinical symptoms of an acute, episodic attack
Prior to the use of newer agents, fresh-frozen plasma (FFP) was administered for
acute HAE attacks. Besides FFP, other treatments had included an increase in androgen
dosing and antifibrinolytic medications, such as
tranexamic acid or
epsilon-aminocaproic acid (EACA).2
Abdominal and laryngeal attacks
Abdominal and laryngeal attacks can be more severe and more dangerous than other types of acute attacks.
For abdominal attacks, treatment should be initiated as soon as possible to avoid
pain and disruption of the patient's life. Pain medications may also be helpful
during abdominal attacks. It is vital that treatment of laryngeal attacks
be initiated at the first signs of such an attack (eg, dysphagia, hoarse voice).
In severe cases, intubation or tracheotomy may be necessary for laryngeal attacks.6
Short-term prophylaxis is generally adminsitered to patients who need to undergo
a surgical or dental procedure. Short-term prophylactic therapy may include C1-INH,
attenuated androgens, or tranexamic acid. C1-INH infusions can be given 1-6 hours
before the procedure. If androgens are used, they are typically administered 5 days
before the procedure and continued for 2 days afterward.6
The Canadian guidelines differentiate short-term treatment based on whether a procedure
is a mild manipulation, such as minor dental work, or a more major procedure, such
as intubation or surgery.
Prophylactic administration of antifibrinolytic agents (tranexamic acid or EACA)
and/or synthetic attenuated androgens (danazol or stanozolol) has proven useful
in reducing the frequency or severity of attacks. However, long-term use of danazol
or stanozolol could produce adverse reactions, including virilization and arterial
hypertension. Six-month liver function tests, annual lipid profiles, and biennial
hepatic ultrasound are recommended follow-ups for these patients2,12
because these medications increase production of C1-INH in the liver and may result
in undesirable side effects, such as:4
- Virilization, including hair loss and male pattern baldness
- Testicular atrophy
- Voice changes
- Hepatic adenomas, hepatocellular carcinoma, and peliosis hepatis
- Aggravation of cardiovascular disease, by lowering levels of high-density lipoprotein
At times, some of these effects are irreversible.
C1-INH will also reduce the frequency of attacks.
Additional considerations in the treatment of patients with HAE include:
- Monitoring of "trigger" medications: because various medications, such as
oral contraceptives, hormone replacement therapy, and ACE inhibitors, can contribute
to the onset of attacks, medication history and selection should be carefully reviewed
when treating patients with HAE attacks.6
- Dental or surgical procedures: as mentioned above, short-term prophylaxis
should be considered for patients scheduled to undergo a dental or surgical procedure.6
- Pregnancy: during pregnancy, women are treated for pain relief (as needed).
During pregnancy symptoms of HAE attacks may stay the same, worsen or improve. Attacks
may increase during the third trimester. Prophylaxis with TXA is acceptable. Androgen
therapy is contraindicated. C1-INH can be used for the treatment of acute attacks.8