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

Prior to 2010, there was no replacement therapy readily accessible in Canada for acute attacks of HAE. Berinert® is the first and only C1 esterase inhibitor available in Canada since October 2010.

  • Berinert® (C1 Esterase Inhibitor, Human) is indicated for the treatment of acute abdominal or facial attacks of hereditary angioedema (HAE) of moderate and severe intensity.


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 for many years. The 2010 Canadian Approach calls for C1-INH dosing based on the patient’s body weight.5

Prior treatments

Prior to the use of C1-INH, solvent detergent plasma and fresh-frozen plasma (FFP) were administered for acute HAE attacks. Otherwise, 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


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. For more information, click (here).

Long-term prophylaxis

Prophylactic administration of antifibrinolytic agents (tranexamic acid or EACA) and/or synthetic attenuated androgens (danazol) 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.5
  • Dental or surgical procedures: as mentioned above, short-term prophylaxis should be considered for patients scheduled to undergo a dental or surgical procedure.5
  • 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


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