Tranexamic Acid for Angioedema
Tranexamic acid (TXA) is primarily indicated as a second-line long-term prophylactic agent for hereditary angioedema (HAE) when first-line C1-inhibitor therapies are unavailable, but it has no established role in acute treatment of angioedema attacks and is NOT recommended for histamine-mediated or allergic angioedema. 1
Role in Hereditary Angioedema (HAE)
Long-Term Prophylaxis (Primary Indication)
TXA should be considered for long-term prophylaxis in HAE patients when C1-inhibitor replacement therapy is unavailable or inaccessible. 1 The mechanism involves inhibition of plasminogen conversion to plasmin, thereby reducing bradykinin formation. 2
Dosing for long-term prophylaxis:
- Adults: 30-50 mg/kg/day in 2-3 divided doses, maximum 3-4 g daily 1, 3
- Children: 15-25 mg/kg twice or three times daily (maximum 3 g/day), adjusted for gastrointestinal tolerability 1, 3
Efficacy is variable but can be substantial: In a study of 37 patients with non-histaminergic angioedema, 75% reduction in attack frequency was achieved in 46% of patients, though approximately 27% showed minimal benefit. 4, 1 TXA appears less effective than attenuated androgens but has a significantly better safety profile. 5, 1
Short-Term Prophylaxis (Limited Role)
TXA may be considered for procedural prophylaxis, though its efficacy is questionable and androgens appear more effective for this indication. 1 If used, dosing is 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
Acute Treatment (NOT Recommended as Monotherapy)
TXA is NOT effective as monotherapy for acute HAE attacks. 5 Standard angioedema treatments including epinephrine, corticosteroids, and antihistamines are ineffective for HAE because the mechanism involves bradykinin, not histamine. 5
There are isolated case reports of TXA use (1g every 6 hours) combined with icatibant for severe bradykinin-mediated angioedema with airway obstruction, but this represents off-label emergency use rather than standard practice. 6
Role in ACE Inhibitor-Induced Angioedema
The evidence for TXA in ACE inhibitor-induced angioedema is extremely limited, consisting only of case reports. 2 While the theoretical mechanism is sound (both conditions involve bradykinin), there are no controlled trials supporting this use. This remains investigational and should not be considered standard therapy. 2
Special Populations
Pregnancy and Lactation
TXA can be considered for HAE prophylaxis during pregnancy, preferably after the first trimester, when C1-inhibitor is unavailable. 1, 7 It can also be used during breastfeeding with appropriate risk-benefit assessment. 7
Pediatric Patients
TXA should be the preferred drug for long-term HAE prophylaxis in children when first-line agents are unavailable due to its superior safety profile compared to androgens. 1
Safety Profile and Contraindications
TXA has a very high safety profile with primarily digestive side effects (nausea, diarrhea, gastrointestinal discomfort). 1, 8, 4
Relative contraindications include:
- Recent thrombosis 1
- Atrial fibrillation 1
- Known thrombophilia 1
- History of thromboembolic events during pregnancy 7
No thromboembolic events were observed in the 37-patient maintenance study, though hypersensitivity reactions have been rarely reported. 4, 8
Critical Limitations
TXA is not FDA-approved specifically for HAE but is approved as an antifibrinolytic agent. 1 It represents the least effective of the prophylactic modalities for HAE when compared to C1-inhibitor replacement and androgens. 5 However, its low cost, excellent tolerability, and high safety profile make it valuable in resource-limited settings or when other options are contraindicated. 1, 4