Hereditary Angioedema (HAE)

Patients with hereditary angioedema (HAE) experience recurrent and unpredictable episodes of swelling of the mucous membranes and subcutaneous tissues of the face, extremities, abdomen, and larynx.¹ The swelling can be life-threatening when it affects the upper airway because laryngeal edema can result in airway obstruction and respiratory failure.^2,3 Most commonly, the symptoms of HAE are due to low blood levels of the C1-esterase inhibitor (C1-INH) protein or C1-INH dysfunction as a consequence of abnormalities of the SERPING1 gene.¹

Many triggers can precipitate an HAE attack. For example, surgical trauma or dental work may lead to respiratory distress, impairment of the airway, and possibly hemodynamic instability.² An episode of HAE may also develop preoperatively.³ It is therefore important that periprocedural planning be undertaken to prevent acute episodes of HAE and decrease associated morbidity and mortality.

Preventive medical care (eg, colonoscopies, dental procedures, breast examinations) is encouraged because it may reduce the need for additional invasive medical procedures that can increase the likelihood of an attack of HAE.⁴

Preparation for Surgery and Medical Procedures

Perioperative management includes the early identification of potential triggers and symptoms because many gastrointestinal attacks, for example, resemble other acute medical conditions and lead to unnecessary surgeries.⁵ The correct management of symptoms, which may involve endotracheal intubation, is essential, as is ongoing prophylactic treatment with the goal of preventing acute episodes.³ The medical team performing the surgery or other relevant medical procedure should be made aware of the patient’s clinical presentation, current pharmacologic management, and treatments for previous episodes.³ 

The avoidance of triggers is the preferred preparation for a medical procedure. General anesthesia and intubation should not be used, if possible, and minimally invasive surgery should be planned, if feasible, to decrease the chance of trauma. Local anesthetics and twilight sedation can be administered instead.⁴ However, not every patient is a candidate for these approaches, and short-term prophylaxis may be required.⁴

Pharmacologic Prophylaxis for Medical Procedures

Short-term prophylaxis should be considered for patients with HAE who must undergo medical procedures involving the upper airway, such as dental work and intubation.⁶ Patients receiving long-term prophylaxis should continue their medication.³

Replacement therapy with plasma-derived C1-INH concentrates is frequently recommended for patients undergoing procedures that mechanically affect the upper way, either alone or in addition to other prophylactic medication.^3,4,6 C1-INH replacement is administered intravenously close to the time of the procedure, usually within an hour before.^3,4 The recommended dose is not yet established; however, a dose of 1000 U or 20 U/kg is often prescribed.⁶ 

Alternatives to C1-INH concentrates if these are not available include fresh frozen plasma (FFP).⁶ Recombinant formulations of C1-INH may also reduce post-procedure attacks and can be considered when plasma-derived medication is not available. Androgens such as danazol may be administered up to 5 days before a procedure and up to 3 days afterward.⁶ However, the frequent use of short courses of androgen therapy may cause the side effects that usually develop during long-term use.⁶ Although it was previously given for short-term prophylaxis, tranexamic acid is not currently recommended before medical procedures.⁶

Patients should be monitored continuously during the postoperative period. They should be made aware that short-term prophylaxis may not be effective, and that angioedema may develop within up to 3 days after the surgery or procedure.³ It is important to educate patients to recognize potential symptoms of HAE before they are discharged.⁷ Additionally, and according to recent guidelines, they should be instructed to carry 2 doses of medication for on-demand self-administration if needed.⁶ The medical team should ensure that the medication is available to the patient following discharge.⁴

References

1. Busse PJ, Christiansen SC. Hereditary angioedema. N Engl J Med. 2020;382(12):1136-1148. doi:10.1056/NEJMra1808012

2. L Vilaça MJ, M Coelho F, Faísco A, Carmona C. Anesthetic considerations for a patient with hereditary angioedema – a clinical case. [Article in Portuguese] Rev Bras Anestesiol. 2017;67(5):541-543. doi:10.1016/j.bjan.2015.03.005

3. Sebastian R, Tobias JD. Perioperative care of a patient with hereditary angioedema. Pediatr Anesth Crit Care J. 2014; 2(1):19-25. doi:10.14587/paccj.2014.5

4. Craig T. Triggers and short-term prophylaxis in patients with hereditary angioedema. Allergy Asthma Proc. 2020;41(Suppl 1):S30-S34. doi:10.2500/aap.2020.41.200058

5. Williams AH, Craig TJ. Perioperative management for patients with hereditary angioedema. Allergy Rhinol (Providence). 2015;6(1):50-55. doi:10.2500/ar.2015.6.0112

6. Maurer M, Magerl M, Betschel S, et al. The international WAO/EAACI guideline for the management of hereditary angioedema-the 2021 revision and update. Allergy. 2022. Epub ahead of print. doi:10.1111/all.15214

7. Zanette G, Stellini E, Sivolella S, Bacci C, Facco E. Hereditary angioedema and anxiety in oral surgery: a case series report. Quintessence Int. 2015;46(5):417-422. doi:10.3290/j.qi.a33180

Reviewed by Kyle Habet, MD, on 6/30/2022.

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Diana Diez Gaspar, PharmD, PhD

Diana earned her PhD and PharmD with distinction in the field of Medicinal and Pharmaceutical Chemistry at the Universidade do Porto. She is an accomplished oncology scientist with 10+ years of experience in developing and managing R&D projects and research staff directed to the development of small proteins fit for medical use.