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hereditary angioedema (HAE)

see also:


  • hereditary angioneurotic oedema is an autosomal dominant condition caused by either a reduced (type I) or dysfunctional (type II) C1-esterase inhibitor (C1-INH) which is a blood protein enzyme which normally inhibits the kallikrein-mediated cleavage of HMW kininogen to bradykinin
  • the uncontrolled production of bradykinin results in angioneurotic oedema.
  • bradykinin is normally cleaved to inactive fragments with a half life of 15secs by kinase I and II which is angiotensin converting enzyme - obviously, the half life will be prolonged in patients on ACE inhibitors.
  • the angioedema often affects the lips, tongue, pharyngeal structures or larynx with potentially life threatening airway compromise.
  • may also:
    • affect the bowel wall causing abdominal pain.
    • be associated with bronchospasm, vasodilatation, hypotension, reflex teachycardia.
  • an attack usually lasts 2-5 days
  • acute episodes of angioedema may be triggered by infection, stress, menstruation, surgery, dental work, trauma and some medicines (including oestrogen-containing contraceptives and ACE-inhibitors) or may have no clear trigger.
  • it is thought to affect some 500 patients in Australia.


  • HAE is diagnosed by the finding of low C1 esterase inhibitor level or function.


  • surgery or any traumatic procedure of the oropharyngeal area such as dental work should be carefully planned.
  • the use of a prophylactic agent prior to such procedures reduces the risk of precipitating angioedema.
  • consult with an immunologist and ICU before the procedure
  • consider GA with endotracheal intubation for oropharyngeal procedures

for planned procedures

  • danazol is the first choice of prophylactic agent
  • 10mg/kg/day for 5-10 days before and 2-5 days after the procedure

for emergency or high risk procedures

C1 esterase inhibitor concentrate (Berinert)
  • 25 units/kg infusion given 1 hour prior to procedure


  • supportive care and close observation, preferably in an area with resuscitation facilities
  • antihistamines and corticosteroids have no role in the management of HAE related angioedema.
  • adrenaline may have a role in Rx as for anaphylaxis
  • C1 esterase inhibitor concentrate infusion (Berinert) may be indicated for severe cases (dose as for prophylaxis above)

bradykinin B2 receptor antagonists

icatibant (Firazyr)

  • introduced in Australia in 2010
  • much more effective than 3 day course of tranexamic acid (12-25mg/kg/dose (max 1.5g) 3-4 times per day)
  • dose: 30mg slow s/cut. injection into abdominal wall
  • most cases respond to a single dose, but a 2nd dose may be given in 6 hours if inadequate relief, or recurrence of symptoms
  • no more than 3 doses in a 24 hour period should be given
  • expensive: ~$AU40 per dose on PBS
  • hypersensitivity to Firazyr
  • ischaemic heart disease - theoretical risk of decrease in coronary blood flow from B2 antagonism
  • stroke in the past few weeks - theoretical possibility that antagonism may attenuate the late phase neuroprotective effects of bradykinin.
  • pregnancy (category C)
  • lactation as it it excreted in milk - thus recommended to discard milk within 12 hours of injection
  • children - no experience as yet
  • elderly - limited data on its safety
  • concomitant use of ACE inhibitors - patients with HAE should not be on ACEI's anyway.
adverse effects
  • injection site reactions - pain, burning, swelling, erythema
  • raised CK level
  • prolonged prothrombin time
  • dizziness, headache
  • asthma, cough, nasal congestion, urticaria, muscle spasms and hot flushes were uncommonly reported
hae.txt · Last modified: 2021/02/11 02:04 by gary1

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