SGEM#395: Too Much Blood from My Nose – Will TXA Help?

TXA is a synthetic derivative of lysine that inhibits fibrinolysis and thus stabilizes clots that are formed. It has been tried in several medical conditions and been reviewed on the SGEM. There is also a short YouTube video discussing the evidence for TXA.

• Trauma (CRASH-2): 1.5% absolute mortality benefit (SGEM#80)
• Isolated TBI (CRASH-3): No statistical difference in mortality (SGEM#270)
• Post-Partum Hemorrhage (WOMAN): No statistical difference in primary outcome (SGEM#214)
• Gastrointestinal Bleeding (HALT-It): No statistical difference in primary outcome (SGEM#301)
• Intracranial Hemorrhage (TICH-2 & ULTRA): No superiority for good neuro outcome (SGEM#236 and SGEM#322)

That first SGEM episode on using TXA for epistaxis showing favorable results also discussed eleven questions concerning epistaxis. It’s a good overview on the management of epistaxis. The episode included the Dundee protocol for adult epistaxis management from 2012.

A second RCT from the same group looked at TXA for adults with anterior epistaxis who were also taking antiplatelet medications. This too showed impressive results claiming superiority of TXA(SGEM#210).

When the NoPAC trial was published, it curbed some of the enthusiasm for TXA in epistaxis (SGEM#321). It was the largest double-blinded RCT (N=496), and found no reduction in the need for anterior packing with the use of intranasal TXA. However, this trial included patients who had already failed 10 min of pressure and 10 min of packing with a topical vasoconstrictor. They also used a lower dose of TXA in the noPAC study. Another issue was that 65% of the patients were taking anticoagulants. Lastly, the primary outcome was different than the previous two RCTs claiming efficacy.

These conflicting results have led to uncertainty regarding the use of TXA in patients with epistaxis. Hosseinialhashemi et al sought to provide some clarity with their trial looking at TXA in uncomplicated anterior epistaxis.

Clinical Question: Should we use TXA for uncomplicated anterior epistaxis?

Reference: Hosseinialhashemi et al. Intranasal Topical Application of Tranexamic Acid in Atraumatic Anterior Epistaxis: A Double-Blind Randomized Clinical Trial. Ann Emerg Med. 2022

• Population: 18-year-old and older, stable patients with atraumatic anterior epistaxis, without bleeding disorders or anticoagulation.
  • Excluded: Posterior bleeds, hemodynamically unstable, allergic to TXA; known nasopharyngeal, nasal cavity, or paranasal malignancy; pregnancy; the experience of out-of-hospital nasal packing; and epistaxis caused by trauma, known bleeding disorders, recent use of anticoagulation drugs or clopidogrel and patients who were prisoners.
• Intervention: Cotton pledgets soaked in TXA 500mg, phenylephrine 0.05g and lidocaine 10% x five sprays. Packing was removed after 15 minutes
• Comparison: Cotton pledgets without TXA but still soaked in phenylephrine 0.05g and lidocaine 10% x five sprays
• Outcome:
  • Primary Outcome: Need for anterior nasal packing
  • Secondary Outcomes: ED length more than 2h, needing electrical cauterization, rebleeding within 24h, rebleeding within 1-7 days.
• Type of Study: Single-center, double-blind RCT in a specialized ENT ED in Iran.

Authors’ Conclusions: “Intranasal topical application of tranexamic acid is associated with a lower rate of need for anterior nasal packing and a shortened stay in the ED; it may be considered a part of the treatment for atraumatic anterior epistaxis.”

Quality Checklist for Randomized Clinical Trials:

1. The study population included or focused on those in the emergency department. No
2. The patients were adequately randomized. Yes
3. The randomization process was concealed. Yes
4. The patients were analyzed in the groups to which they were randomized. Yes
5. The study patients were recruited consecutively (i.e. no selection bias). Yes
6. The patients in both groups were similar with respect to prognostic factors. Yes
7. All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Yes
8. All groups were treated equally except for the intervention. Yes
9. Follow-up was complete (i.e. at least 80% for both groups). Yes
10. All patient-important outcomes were considered. Yes
11. The treatment effect was large enough and precise enough to be clinically significant. Yes
12. Financial conflicts of interest. No

Results: They screened 315 patients and enrolled 240 patients. The patients were divided in two groups in a 1:1 ratio. The mean age of participants was 52 years, 52.5% were male and 30% were on aspirin.

Key Results: TXA was superior to usual care for adult patients presenting with anterior epistasis.

• Primary Outcome: Need for anterior packing
  • TXA Group 50.0% vs No TXA group 64.2% (NNT 7)
  • Odds Ratio [OR], 0.56; 95% confidence interval [CI], 0.33 to 0.94.
• Secondary Outcomes: 
  • No statistical differences between the two groups in terms of the need for electrical cauterization and the rate of rebleeding within 1 to 7 days.
  • TXA was associated with a lower rate of stay in the ED for more than 2 hours (9.2% vs 20.8%) OR 0.38 (95% CI, 0.18 to 0.82) and rebleeding in 24 hours (15.0% vs 30%) OR 0.41 (95% CI, 0.22 to 0.78) compared with the rates in the control group.

1. Selection Bias: These were patients that from an ENT emergency department of a referral academic-teaching otolaryngology center. It is unclear if these represent the same patients who present to a community emergency department. You could argue that patients with more severe nose bleeds would present to this subspecialized ED. If TXA works in these cases than it should work in milder cases. Or if disease severity is lower than the impact of TXA might be less and not be statistically different from usual care.

2. External Validity: The second point is related to the first nerdy point. This was not only a specialist ENT ED, but it was also a single centre study in Iran. The patient population may not have external validity to patients we see in our own EDs?

3. Standard Care: Standard care in Iran may differ from our standard care. Some places like to apply ice packs, or use different external devices to stop bleeding and a variety of intranasal medications.

4. Electric Cautery: After the treatment in both groups, bipolar cauterization was used when there was a visible bleeding site in the anterior part of the nasal cavity. Many patients required electric cautery in this trial. This included about two-thirds of the patients in both groups.

This result is much higher than in my practice experience. It further suggests that these are selected patients with more severe disease and/or Iran has a different standard practice. In addition, electric cautery is not available where I’ve worked in multiple sites in Ontario, Canada. Perhaps those in the UK, USA, Europe, Australia/NZ and elsewhere could respond about their use of electric cautery.

Electric cautery could have some potential harms. These direct harms or any other harms/adverse events were not mentioned in the manuscript. It is an unfortunate trend for studies either to under-report or not report harms at all.  How can clinicians and patients make an informed decision with only knowing the potential benefits and not knowing the potential harms?

5. Other Situations: This trial is silent on other clinical situations of epistaxis which are routinely encountered in the ED. This includes traumatic bleeding, patients on anticoagulants drugs or patients who represent to the ED with refractory bleeding.

Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors’ conclusions but would have made a friendly amendment to qualify that it was in a select population at a subspecialized ENT ED in Iran.

SGEM Bottom Line: It is reasonable to add TXA to your cotton pledgets for adults with uncomplicated anterior epistaxis.

Case Resolution: Jim blew out his nose and you applied cotton pledgets soaked with vasoconstricting solution and TXA. His epistaxis resolved without the need for anterior packing. You provide him instructions to avoid nose picking, you improved patient satisfaction and ED flow.

Clinical Application: If TXA is rapidly available, consider adding it to patients with atraumatic anterior epistaxis in your cotton pledgets. An NNT 7 for decreasing the need for anterior packing is clinically important, TXA is cheap, and a single topical application is very unlikely to cause harm.

Dr. Dominique Trudel

What Do I Tell the Patient?  Blow your nose to remove some of the blood. Then we will put a cotton pack up your nose. It will have two medications on the cotton. One medication stops bleeding by pinching off the blood vessels. The other medication stops bleeding by helping your body form a clot/scab. We will leave the packing in for 15min to see if it works. After 15 minutes it will be pulled out. If you are not bleeding, you can be on your way with some advice. If it is bleeding, we will pack it, send you home and see you back tomorrow.

Keener Kontest: Last weeks’ winner was Kevin Burns a PA from New Haven CT. He knew PAs can practice in Manitoba, Ontario, New Brunswick, Alberta and Nova Scotia.

Listen to the SGEM podcast to hear this weeks’ question. Send your answer to TheSGEM@gmail.com with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.

Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.