Why is Tranexamic acid (TXA) given for angioedema?

Why Tranexamic Acid is Given for Angioedema

Tranexamic acid (TXA) is given for hereditary angioedema (HAE) primarily as long-term prophylaxis to reduce attack frequency, particularly when first-line C1-inhibitor therapies are unavailable, and is especially preferred in children, pregnancy (after first trimester), and resource-limited settings due to its favorable safety profile. 1

Mechanism of Action

TXA works as an antifibrinolytic agent by inhibiting the conversion of plasminogen to plasmin, which is a key step in kallikrein activation and bradykinin formation—the primary mediator of angioedema in HAE. 2 This mechanism addresses the underlying pathophysiology of bradykinin-mediated angioedema. 3

Clinical Indications and Efficacy

Long-Term Prophylaxis (Primary Use)

• TXA should be considered as long-term prophylaxis (LTP) when first-line C1-inhibitor therapies are unavailable, either alone or in combination with attenuated androgens. 1
• The recommended dosing is 30-50 mg/kg/day in 2-3 divided doses, with a maximum of 3-4 g daily. 1
• In a study of 37 patients with non-histaminergic angioedema, 75% reduction in attack frequency was achieved in 17 patients (46%) treated with TXA over 6 months, with no patients experiencing increased symptoms. 4
• Long-term effectiveness has been demonstrated in patients treated for 8-34 months without adverse effects on hepatic function or fibrinolytic activity. 5

Short-Term Prophylaxis (Limited Efficacy)

• TXA may be considered for short-term prophylaxis before procedures, but its efficacy is questionable for this indication. 1
• When used for short-term prophylaxis, doses of 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 have been suggested. 1
• Androgens appear more effective than TXA for short-term prophylaxis. 1

Acute Attack Treatment (Controversial)

• TXA used acutely during an ongoing attack has been reported to potentially prolong the attack. 1
• However, some patients report benefit when TXA is used very early during a well-defined prodromal period or immediately at attack onset, particularly for milder attacks (peripheral edema, less severe abdominal attacks). 1
• High-dose oral or IV TXA (1000 mg every 3-4 hours for 12-18 hours) may be effective for milder attacks, though trial data is very limited. 1

Special Populations

Children

• TXA should be the preferred drug for long-term prophylaxis in children when first-line agents are unavailable. 1
• Pediatric dosing is 15-25 mg/kg twice or three times daily (maximum), adjusted for gastrointestinal tolerability and efficacy. 1, 6
• TXA is preferred over androgens in children due to the high side effect burden of androgens, including virilization and precocious puberty. 1

Pregnancy and Breastfeeding

• TXA can be considered for HAE prophylaxis during pregnancy, preferably after the first trimester, when C1-inhibitor is unavailable. 1, 7
• Evidence of safety regarding teratogenicity and thrombosis risk is lacking, but case reports suggest it may be helpful. 1
• TXA can be used in breastfeeding mothers with appropriate risk-benefit consideration. 7

Safety Profile and Advantages

• TXA is well-tolerated, inexpensive, and has a very high safety profile compared to attenuated androgens. 1, 3, 4
• Main side effects are digestive in nature (nausea, diarrhea, gastrointestinal discomfort). 1, 4
• No thromboembolic events were observed in the 37-patient maintenance study, and hepatic function remains unaffected with long-term use. 5, 4
• Hypersensitivity reactions are rare but have been described. 3

Important Caveats

• Recent thrombosis, atrial fibrillation, or known thrombophilia are relative contraindications. 6
• TXA is not FDA-approved specifically for HAE but is approved as an antifibrinolytic agent. 1
• Efficacy is variable—while some patients achieve excellent control, approximately 27% in one study showed minimal reduction in attacks. 4
• TXA is considered a second-line or alternative therapy when C1-inhibitor replacement, icatibant, or ecallantide are unavailable. 1