Winning EEM 2022 Post! | TXA for Epistaxis – Clinical Controversy

Winner EEM 2022 Blog Post Competition!

Congratulations to Dr. Matthew Stampfl, University of Wisconsin School of Medicine, on being the winner of the Essentials of Emergency Medicine 2022 blog post contest. Here is his winning post! Enjoy.

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Written by Matthew Stampfl

The Controversy | Topical TXA for Epistaxis
An 83-year-old male with history of dementia and atrial fibrillation on warfarin comes in with bleeding from the nose for the past 90 minutes. Direct pressure doesn’t seem to have helped, but his caregiver really wants to avoid packing if possible, since he became extremely agitated last time he received it. Your attending says to pull out the vial of TXA, but you ask: “Wait, wasn’t there a recent study that found TXA didn’t help?”

The Case for TXA
TXA is a fixture in algorithms for epistaxis, including a recent one promulgated by the New England Journal of Medicine. This is based on multiple smaller studies showing promising efficacy.

For instance, a 2018 RCT included 124 patients with epistaxis on antiplatelet agents and compared topical TXA (500 mg) on a pledget to topical lidocaine-epinephrine on a pledget followed by nasal packing. Patients were only eligible for inclusion if 20 minutes of direct pressure failed to resolved their symptoms. The primary outcome was cessation of bleeding within 10 minutes, which occurred 73% of the time in the TXA group vs 29% in the lidocaine-epinephrine/nasal packing group.

Another RCT in 2019 took 135 patients and split them between three arms: atomized TXA (500 mg) with compression, nasal packing with Merocel, and compression alone. Primary outcome was cessation of bleeding within 15 minutes. This occurred 91.1% of the time in the TXA arm vs 93.3% in the Merocel packing arm and 71.1% in the compression alone group. On analysis, both TXA and Merocel were significantly better than placebo, though they were not different from each other.

The Argument Against
However, the largest RCT (NoPAC, 2021) on TXA in epistaxis comes to a different conclusion. It was a double-blinded multicenter RCT which enrolled 496 patients with epistaxis that failed to resolve with 10 minutes of direct pressure followed by topical vasoconstrictor application and then another 10 minutes of direct pressure. Patient were randomized between TXA or saline delivered via cotton wool dental rolls (the UK’s equivalent to pledgets). The protocol called for 200 mg TXA soaked into the dental roll which was held in place in the nare via nasal clip for ten minutes. If this did not control the bleeding, the treatment would be repeated once. Primary outcome in this trial was need for anterior nasal packing, which was placed at the discretion of the treating clinician. There was no significant difference in rates of packing between the groups, with 43.7% of the TXA undergoing packing vs. 41.3% of the placebo group.

My Take and Recommendations
So where does this leave us? We want to be evidence-based, and the largest study on the topic calls into question whether TXA in epistaxis improves outcomes. On the other hand, we know our 83-year-old won’t tolerate packing well, and we would like to spare him (and us) that experience if possible.

Digging into the NoPAC trial reveals a few differences that might contribute to its divergent findings. For one, TXA was given as a 200 mg dose x 2 rather than the single 500 mg used elsewhere. Moreover, all patients enrolled in NoPAC had to first fail a topical vasoconstrictor, which potentially selects a somewhat different patient population. Finally, NoPAC was conducted in the UK, which may limit generalizability to the US given practice variation (e.g. UK patients who undergo nasal packing are admitted for an average of three days). 

A 2021 systematic review of topical TXA in epistaxis included 1,299 patients across 8 studies (including NoPAC). Unfortunately, NoPAC was excluded from the analysis of bleeding cessation because its outcome was avoiding packing, but the remaining trials showed that TXA had 3.5 times greater odds of bleeding control at first reassessment.

Thus, the evidence isn’t clear. But as with all treatments we provide to our patients, we have to weigh the risks and benefits. On the benefit side of the ledger, it is unclear if TXA will help this patient to avoid packing. Conversely, topical TXA has minimal adverse effects, is quite inexpensive and won’t take long to trial. Given the negligible downsides of TXA and the known harms of packing this patient, let’s give TXA a try!