TXA: Still a Gold Medal for Stopping the Bleed?

TXA – Mechanism and Evidence: 

TXA (trans-4-(aminomethyl)cyclohexane carboxylic acid) is a synthetic lysine amino acid derivative that inhibits both plasminogen activation and plasmin activity that leads to inhibition of fibrinolysis. TXA slows down tissue-plasminogen-activator mediated conversion of plasminogen to plasmin. Also, it occupies the lysine binding sites on both plasminogen and plasmin, preventing clot breakdown.

The utility of topical TXA has been demonstrated in various case reports, small studies, and systematic reviews. Most trials favoring the use of topical TXA for the management of epistaxis were small, single-center studies. These small studies showed that topical TXA was a viable agent in the management of epistaxis in the ED.

A study by Zahed and colleagues found that patients who received TXA (500 mg/5 mL soaked in a cotton pledget, n = 107) more frequently achieved cessation of bleeding within 10 minutes, discharge within two hours, and experienced less rebleeding in 24 hours compared to patients who received usual care (n = 109). This was followed by multiple studies evaluating TXA for epistaxis in the ED in patients taking antiplatelet agents which showed success in using TXA compared to standard of care.  

Additional randomized trials and retrospective studies continued to support the efficacy of TXA in epistaxis compared to standard therapies, such as local vasoconstrictors and nasal packing, as well as oxymetazoline. Due to these consistent positive findings, TXA gained extensive popularity in the management of epistaxis in the ED; however, in 2021, the largest randomized control trial evaluating TXA in this patient population was published and results from this trial have led to less certainty about TXA’s utility for this condition. 

Hot-off the Press: 

In a study conducted in 26 EDs in the United Kingdom (NoPAC trial), investigators looked to test the effectiveness of topical intranasal TXA in reducing the need for anterior nasal packing in adult patients presenting to the ED. This study randomized 496 patients; 254 in the TXA group and 242 in the placebo group. All patients were treated with a topical vasoconstrictor (phenylephrine or dilute epinephrine) for 10 minutes followed by TXA or placebo. TXA treatment consisted of 4 mL (100 mg/mL) given in up to two divided doses of 2 mL. The remaining 2 mL were placed in the same manner if bleeding persisted. 43.7% (111/254) of patients in the TXA group required nasal packing compared to 41.3% (100/242) in the placebo group (p = 0.59). Hospital admission, length of hospital stay, blood transfusion, and recurrent epistaxis was similar between groups. The authors concluded that in patients presenting to the ED with atraumatic epistaxis that is uncontrolled with simple first-aid measures and a topical vasoconstrictor, topical TXA is no more effective than placebo at controlling bleeding and reducing the need for anterior nasal packing. Some caveats should be noted; all patients received a topical vasoconstrictor prior to randomization, the dose of topical TXA was lower compared to other studies, 25% of patients were managed with silver nitrate cautery, and > 60% of patients in each group were on anticoagulation. While this is the most rigorous study regarding the use of topical TXA in the management of epistaxis, based on the totality of the evidence, TXA may still be considered in the armamentarium of agents to combat epistaxis.

The most common dose used of TXA is 500 mg/5 mL soaked onto a cotton pledget and administered to the bleeding nostril. The intravenous formulation may be used for this indication and applied topically. Other agents that may be used in the management of epistaxis include topical vasoconstrictors such as oxymetazoline and phenylephrine.