Clinical Management of HAE
Clinical management of
hereditary angioedema (HAE) is complex and includes avoiding potential
triggers, management of acute attacks, and prophylaxis.
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,
frequent, or life-altering attacks. 5
Acute attacks
Unlike in Canada and Europe, prior to 2009 there were no specific treatments available
in the United States for acute attacks of HAE. However, there are now 2 treatment
options:
- Complement-1 esterase inhibitor protein
(C1-INH) concentrate for acute abdominal and facial attacks in adults and
adolescents.12,14
- Plasma
kallikrein inhibitor for acute HAE attacks in individuals 16 years of age
and older.15,16
C1-INH
C1-INH therapy works by replacing the missing or malfunctioning C1-INH protein in
patients with a C1-INH deficiency.12
Although adverse events are uncommon, the most frequent from the clinical trial
included nausea, diarrhea, abdominal pain, and muscle spasms.12,15
C1-INH has been used in Europe and Canada for many years. The 2010 Canadian Approach
calls for C1-INH dosing based on the patient’s body weight.5
Kallikrein inhibitor
A kallikrein inhibitor works by blocking the generation of kallikrein and its byproduct,
bradykinin, which is thought to cause HAE attacks.18
The therapy is generally well-tolerated, but side effects of dizziness, fatigue,
headache, nausea, and vomiting have been reported.15
There have been reports of anaphylaxis associated with the administration of this
therapy, therefore it carries a black box warning for anaphylaxis.
Prior treatments
Prior to the use of C1-INH and kallikrein inhibitor, 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). 5,12
Abdominal and laryngeal attacks
Abdominal and laryngeal attacks can be more severe 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. Likewise, treatment of laryngeal attacks should be initiated
as soon as there is evidence of such an attack (dysphagia, hoarse voice). At times,
intubation or tracheotomy may be necessary for laryngeal attacks.6
Prophylaxis
Short-term prophylaxis
Short-term prophylaxis is generally limited to patients in unusual circumstances,
particularly those about 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 24 hours before the procedure or just prior to it. If antifibrinolytics
or androgens are used, they are typically administered 5 days before the procedure
and continued for 2 days afterward.
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.
Long-term prophylaxis
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. C1-INH will also reduce the frequency
of attacks.5,6 However, that long-term
use of danazol or stanozolol may result in virilization and arterial hypertension.
Six-month liver function tests, annual lipid profiles, and biennial hepatic ultrasound
are recommended follow-up for these patients4
because these medications increase production of C1-INH in the liver and may result
in undesirable side effects, such as5
- Virilization, including hair loss and male pattern baldness
- Prostatic hypertrophy and prostatic carcinoma
- Gynecomastia
- Voice changes
- Hepatic adenomas, hepatocellular carcinoma, and peliosis hepatis
- Aggravation of cardiovascular disease, by lowering levels of high-density lipoprotein
(HDL)4,6
At times, some of these effects are irreversible.
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.
- Dental or surgical procedures: as mentioned above, short-term prophylaxis
should be considered for patients scheduled to undergo a dental or surgical procedure.
- Pregnancy: during pregnancy, women are treated for pain relief (as needed).
The UK consensus advises against the use of attenuated androgens during pregnancy
and recommends that all prophylaxis be stopped prior to conception. The consensus
does allow the cautious use of tranexamic acid, if needed. C1-INH may be used for
the treatment of severe attacks prior to delivery and in the delivery suite.The
Canadian algorithm concurs that long-term prophylaxis with androgens is contraindicated
during pregnancy and lactation. However, it does allow for the short-term prophylactic
use of danazol during the third trimester of pregnancy.5