Hereditary angioedema attacks cease after tranexamic acid treatment

Key takeaways:

• The patient, aged 66 years, had no previous edema.
• The patient tested positive for a mutation in the plasminogen gene.
• The patient did not experience any attacks for 13 months with treatment.

ANAHEIM, Calif. — A patient with hereditary angioedema and a plasminogen gene mutation did not have any attacks with tranexamic acid, according to a poster at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting.

This total reduction in attack frequency with prophylactic treatment was consistent with results from previous case series, Ryan Friedman, MD, resident in internal medicine at Oregon Health & Science University, said during his presentation.

“Traditionally, hereditary angioedema (HAE) has been characterized by a deficient C1 inhibitor. Recently, HAE with normal C1 inhibitor activity has also been described,” Friedman said.

Multiple mutations that lead to the development of HAE with normal C1 activity have been identified, including a mutation in the plasminogen gene, characterized as HAE-PLG. HAE-PLG can develop at any age, with a 3:1 gender ratio between female and male patients.

Also, Friedman said, HAE-PLG frequently presents with tongue swelling.

“While multiple medications have received FDA approval for HAE prophylaxis for HAE with decreased C1 esterase inhibitor level, there are limited data to guide treatment for patients with HAE with normal C1 inhibitor activity,” Friedman said.

Friedman described a man, aged 66 years, who went to urgent care with a swollen tongue. At the time, he was taking a beta blocker, a calcium channel blocker, a statin and a protein pump inhibitor.

“Prior to this episode, he had never experienced symptoms of edema in his life,” Friedman said.

The swelling resolved without intervention.

“Over the course of the next 9 months, he had eight subsequent ED visits for angioedema symptoms, which ultimately led to three inpatient admissions over concerns for airway swelling, two intubations and one tracheostomy,” Friedman said.

During the first ED visit, the patient’s C1 inhibitors, C4 and tryptase levels all were normal. During the first six visits, he received H1 and H1 antihistamines, fresh frozen plasma, glucocorticoids and epinephrine, all without any measurable improvement.

Also, the patient received a C1 inhibitor concentrate while he was intubated during his seventh and eighth ED visits.

The patient’s mother had experienced tongue swelling, and his son had died in his 20s from asphyxia secondary to upper airway obstruction. Genetic testing was offered to all the patient’s living relatives, but it was only performed for him and for his sister.

The patient and his sister both tested positive for the HAE-PLG mutation in the plasminogen gene, but she had never experienced any symptoms concerning for angioedema.

The patient then began prophylactic tranexamic acid (TXA) treatment, and he did not experience any recurrent edema for the next 13 months.

The exact mechanism underlying the pathogenesis of HAE for patients with HAE-PLG is unknown, Friedman said, but the mutation is believed to increase plasminogen activation, increasing plasmin-derived bradykinin.

“TXA is thought to interfere with this by inhibiting the cleavage of plasminogen to plasmin,” Friedman said.

Although rare, Friedman continued, multiple types of HAE can present with normal C1 inhibitor levels.

“When HAE with normal C1 inhibitors is suspected, genetic testing should be sent,” he said.

Also, a previous case series found that three cases of HAE treated with TXA had a mean 93.9% reduction in attack frequency, compared with three cases treated with danazol that had a mean 83.3% reduction and six cases treated with progestins with a mean 46.3% reduction.

“This patient’s 100% reduction in attack frequency with prophylactic TXA was consistent with the results from previous case series, which demonstrated that TXA was highly effective at reducing the frequency of angioedema attacks,” Friedman said.

However, Friedman cautioned, TXA is not a replacement for rescue therapy.

“As such, while it has not received FDA approval for treatment of hereditary angioedema, and comes with an increased risk for thrombotic events, TXA should be considered for prophylactic therapy for patients with HAE-PLG,” he said.