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, frequent, or
    life-altering attacks.6

Acute attacks

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
  • Plasma kallikrein inhibitor for acute HAE attacks in individuals 12 years of age and older.
  • Bradykinin B2 Receptor Antagonist for treatment of acute HAE attacks in adults 18 years or older.

C1-INH

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.

Kallikrein inhibitor

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 of HAE.

Prior treatments

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


Prophylaxis

Short-term prophylaxis

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.

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. 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
  • 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.

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

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