What is the role of Tranexamic acid in the treatment of angioedema?

Tranexamic Acid in Angioedema

Primary Recommendation

Tranexamic acid is an effective second-line agent for long-term prophylaxis of hereditary angioedema (HAE) when first-line C1-inhibitor therapies are unavailable, but it has NO role in the acute treatment of angioedema attacks. 1

Role in Hereditary Angioedema

Long-Term Prophylaxis (Primary Indication)

Tranexamic acid should be used as long-term prophylaxis to reduce attack frequency in HAE patients, particularly when C1-inhibitor replacement therapy is unavailable or unaffordable. 1

• The recommended dosing is 30-50 mg/kg/day divided into 2-3 doses, with a maximum of 3-4 g daily 1, 2
• Approximately 46% of patients achieve a 75% reduction in attack frequency, though efficacy is variable with about 27% showing minimal benefit 1
• In a French study of 37 patients, 75% reduction in attacks occurred in 17 patients (46%), with no patients experiencing increased symptoms 3
• Tranexamic acid appears less effective than attenuated androgens but has a significantly superior safety profile 1

Special Populations Where Tranexamic Acid is Preferred

Tranexamic acid should be the preferred prophylactic agent in children, pregnant women (after first trimester), and resource-limited settings due to its excellent safety profile. 1

• Pediatric dosing: 15-25 mg/kg twice or three times daily (maximum 3 g/day), adjusted for gastrointestinal tolerability 1, 2
• Pregnancy: Can be used after the first trimester when C1-inhibitor is unavailable, as it is safer than androgens which are contraindicated 1
• Tranexamic acid may be particularly effective in HAE-FXII subtype, especially in patients with estrogen-related triggers 4

Short-Term Prophylaxis (Questionable Efficacy)

Tranexamic acid may be considered for short-term prophylaxis before procedures, though androgens appear more effective for this indication. 1

• Suggested dosing: 30-50 mg/kg or maximum 3-4.5 g daily in 2-3 divided doses from 5 days before until 2 days after the procedure 1
• The efficacy for short-term prophylaxis is questionable compared to other options 1

NOT Effective for Acute Attacks

Tranexamic acid is NOT effective as monotherapy for acute HAE attacks and should never be used for this purpose. 1

• Standard angioedema treatments including epinephrine, corticosteroids, and antihistamines are also ineffective for HAE because the mechanism involves bradykinin, not histamine 1, 5
• Acute attacks require plasma-derived C1-inhibitor (1000-2000 U IV) or icatibant (30 mg subcutaneously) 5

Role in ACE Inhibitor-Induced Angioedema

Emerging evidence suggests tranexamic acid may have a role in ACE inhibitor-induced angioedema, though this is not yet guideline-supported. 6, 7

• A retrospective study of 16 patients showed 14 of 14 patients (100%) who received TXA before intubation did not require intubation 7
• The mechanism is logical: TXA inhibits conversion of plasminogen to plasmin, reducing kallikrein activation and bradykinin formation 6
• This indication requires further investigation before routine recommendation 6, 7

Safety Profile and Monitoring

Tranexamic acid is well-tolerated, inexpensive, and has a very high safety profile compared to attenuated androgens. 1

• Main side effects are digestive: nausea, diarrhea, gastrointestinal discomfort 1, 3
• No thromboembolic events were observed in the French study of 37 patients over an average of 20 months 3, 8
• Relative contraindications: recent thrombosis, atrial fibrillation, or known thrombophilia 1
• Unlike androgens, tranexamic acid does not require hepatic monitoring or ultrasounds 5

Regulatory Status

Tranexamic acid is NOT FDA-approved specifically for HAE but is approved as an antifibrinolytic agent. 1

Critical Pitfalls to Avoid

• Never use tranexamic acid for acute angioedema attacks—it requires several days to become effective 1, 5
• Do not substitute tranexamic acid for C1-inhibitor therapy when the latter is available, as C1-inhibitor is more effective 1
• Do not use tranexamic acid in patients with active thrombosis or high thrombotic risk 1
• Recognize that approximately 27% of patients will have minimal response, so reassess efficacy after an adequate trial period 1