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Is topical tranexamic acid superior to standard treatment for epistaxis in adult patients in a prehospital setting – A Literature Review
Introduction
The World Health Organization predicts that the proportion of elderly individuals within the population will increase in the coming years. In just six years, about 16% of the world’s population will be the age of 60 or above (World Health Organization 2024). From the perspective of epistaxis, patients who present with epistaxis are mostly elderly (Walker et al. 2007). Prehospital treatment with tranexamic acid for epistaxis has an unknown opportunity to reduce the number of patients transported to an emergency department. This literature review aims to illuminate the evidence around the prehospital use of tranexamic acid for epistaxis.
After searching four databases (PubMed, Medline, Clinal, and Scopus), no evidence was found about using tranexamic acid for epistaxis in a prehospital seRing. Consequently, this review focused on the administration of tranexamic acid in an emergency department seRing.
Nine papers were found. After reviewing them with JBI’s critical appraisal tools (Moola et al. 2020a; Moola et al. 2020b; Barker et al. 2023), a paRern emerged: tranexamic acid was given as the primary treatment or after the primary treatment failed. Tranexamic acid can be used as the primary drug for epistaxis in a prehospital seRing. Therefore, this literature review divides the articles into primary or additional treatments.
Primary treatment
Patients with epistaxis seen by an ambulance will likely only have normal first aid as a treatment option. Tranexamic acid can be the drug of choice for the aRending prehospital provider.
In Turkey, Sedat Akkan (Akkan et al. 2019) researched the differences between 3 treatment strategies among patients with anterior epistaxis aRending an emergency department. The first strategy was atomised tranexamic acid together with 15 minutes of external compression, and the second strategy was atomised normal saline together with 15 minutes of external compression. The third strategy was the insertion of a Merocel tampon. The primary outcome was the lack of bleeding after 15 min of treatment. Secondary outcomes are the need for rescue treatment and rebleeding within 24 hours. Akkan concluded that there was no statistically significant difference between the tranexamic acid and tampon groups; both groups were superior to the normal saline group. In the tampon group, there was a greater complaint about pain related to the treatment compared to the other groups.
Another study from Turkey (Ekmekyapar et al. 2022) compared tranexamic acid, epinephrine, and lidocaine with anterior nasal packing in patients with anterior epistaxis. The primary outcome was the time it took to stop the bleeding. Secondary outcomes were vital signs and blood parameters. Among the 108 patients included in this study, the authors did not find any statistically significant difference between the three groups with any of the outcomes. Therefore, the authors concluded that all drugs are safe for treating anterior epistaxis.
Close by in northern Iran, researchers (Amini et al. 2021) looked at first-line treatment with tranexamic acid or phenylephrine + lidocaine together with anterior nasal packing. The aimed cohort included patients with anterior epistaxis and were under treatment with aspirin, clopidogrel or both in the emergency department. The primary outcome was bleeding cessation, together with secondary outcomes such as rebleeding within 72 hours
and length of stay in the emergency department. Amini concluded that there was a higher proportion in the tranexamic acid group of bleeding cessation and a decreased length of stay, together with a smaller number of patients with rebleeding.
Kirsten Whitworth (Whitworth et al. 2020) conducted a randomised control trial in the United States, examining the difference between topical atomised tranexamic acid and oxymetazoline for patients with anterior epistaxis in an emergency department. The authors’ primary outcome was hemostasis within 30 minutes. Secondary outcomes included rebleeding in the emergency department within 48 hours, admission, and needing consultation with an ear, nose, and throat specialist. The study’s sample size was small, N=38. Whitworth concluded that tranexamic acid treatment was superior to Oxymetazoline.
These four articles looked at tranexamic acid as a part of the first-line treatment for epistaxis patients. The literature also describes tranexamic acid as an addon if the primary treatment fails.
Additional treatment
Patients who come to an emergency department with epistaxis can be treated with different drugs or simple first aid. This section will concentrate on articles examining tranexamic acid as an additional treatment.
The NoPAC trial (Reuben et al. 2021) looked at adults with epistaxis where standard first aid and topical administration with vasoconstrictors failed to stop the bleeding in an emergency department. The authors conducted a double-blind, randomised control trial. Their primary outcome was reducing the need for anterior nasal packing. Reuben did not distinguish between anterior and posterior epistaxis. The trial did not find any significant difference in the primary outcome. The authors did not find any statistically significant difference among the secondary outcomes.
Asha Birmingham (Birmingham et al. 2018) made a retrospective cohort study. They looked at patients who were treated for epistaxis between September 2014 and August 2016 in an emergency department. Patients who accomplished hemostasis after undergoing simple first aid, followed by the standard administration of lidocaine, epinephrine, or oxymetazoline, were excluded. The authors divided patients into two groups and they were treated with tranexamic acid or not. Their primary outcome is the length of stay in the Emergency department. Secondary outcomes included consultation with an otolaryngologist and anterior nasal packing. The authors did not find a statistically significant difference in the primary outcome. Among the secondary outcomes, there was a decrease in the need for consultation with an otolaryngologist and anterior nasal packing.
In southern Iran, Hosseinialhashemi (Hosseinialhashemi et al. 2022) conducted a double- blind, randomised control trial. The authors added tranexamic acid to their standard care for patients referred to their ears, nose, and throat emergency department from standard emergency departments. Hosseinialhashemi’s primary outcome was a reduction of anterior nasal packing. Secondary outcomes were the length of stay, electrical cauterisation, and rebleeding within 24 or 7 days. The conclusion discovered a reduction in anterior nasal packing, length of stay, and rebleeding within 24 hours. But there was no difference in electrical cauterisation or rebleeding within seven days.
In the capital of Iran, Tehran, Zahed (Zahed et al. 2018) looked at a patient taking aspirin, clopidogrel or both who presented with epistaxis. The study was a single-blind, randomised controlled trial. For patients to be included in the study, the first aid treatment (external compression of both nostrils) had to fail. Patients received either tranexamic acid or epinephrine together with lidocaine for ten minutes. The primary outcome was to see if the bleeding was stopped after ten minutes of intervention. Secondary outcomes included length of stay in ED, patient satisfaction and rebleeding within 24 or 7 days. Overall,
Zahed found favour of tranexamic acid in most outcomes compared to anterior nasal packing.
This review looked at articles treating patients with tranexamic acid as primary or as an additional treatment. In the search of articles, one was found that looked at treatment at home with tranexamic acid.
At home
Most articles have looked at treatment in an emergency department, except one where patients are treated at home.
All studies in this literature review look at either adults or adults and kids. Eshghi (Eshghi et al. 2014) looked at severe epistaxis in paediatrics with inherited coagulopathies. The cohort was divided into three groups, each with a tampon with either tranexamic acid, Chitosan, or Oxidized regenerated cellulose. The parents administered the tampons if the patient got epistaxis. The primary outcome was hemostasis within ten minutes. The authors found that the chitosan-based tampons were superior to the two other tampons. The nine articles have now been described. Some with tranexamic acid as the primary treatment and some with tranexamic acid as an additional treatment for the primary.
Conclusion
With an increasing elderly population and the perspective that most patients with epistaxis are elderly, it is within the healthcare system’s interest to increase the proportion of patients with epistaxis to be treated and left at home. This literature review has found a gap in the literature on administering tranexamic acid for epistaxis in a prehospital seRing. Dividing the articles into two groups, primary and secondary use of tranexamic acid, shows a tendency among the primary grouped articles that tranexamic acid is superior and safe to use compared to normal first aid in an emergency department. This is likely transferable to the prehospital seRing. When tranexamic acid is used in addition to the
primary treatment, the articles in this review do not have the same impact of stopping the bleeding. With the gap described in the literature, further research is needed to determine the relevance of tranexamic acid in treating epistaxis in a prehospital seRing.
References
Akkan, S., Çorbacıoğlu Ş, K., Aytar, H., Emektar, E., Dağar, S. and Çevik, Y. (2019) ‘Evaluating EGectiveness of Nasal Compression With Tranexamic Acid Compared With Simple Nasal Compression and Merocel Packing: A Randomized Controlled Trial’, Ann Emerg Med, 74(1), 72-78, available: http://dx.doi.org/10.1016/j.annemergmed.2019.03.030.
Amini, K., Arabzadeh, A.A., Jahed, S. and Amini, P. (2021) ‘Topical Tranexamic Acid versus Phenylephrine-lidocaine for the Treatment of Anterior Epistaxis in Patients Taking Aspirin or Clopidogrel; a Randomized Clinical Trial’, Archives of Academic Emergency Medicine, 9(1), 1-7.
Barker, T., Stone, J., Sears, K., Klugar, M., Tufanaru, C., Leonardi-Bee, J., Aromataris, E. and Munn, Z. (2023) ‘The revised JBI critical appraisal tool for the assessment of risk of bias for randomized controlled trials’, JBI Evidence Synthesis, 21(3), 494-506.
Birmingham, A.R., Mah, N.D., Ran, R. and Hansen, M. (2018) ‘Topical tranexamic acid for the treatment of acute epistaxis in the emergency department’, Am J Emerg Med, 36(7), 1242-1245, available: http://dx.doi.org/10.1016/j.ajem.2018.03.039.
Ekmekyapar, M., Sahin, L. and Gur, A. (2022) ‘Comparison of the therapeutic eGicacy of topical tranexamic acid, epinephrine, and lidocaine in stopping bleeding in non- traumatic epistaxis: a prospective, randomized, double-blind study’, Eur Rev Med Pharmacol Sci, 26(9), 3334-3341, available: http://dx.doi.org/10.26355/eurrev_202205_28753.
Eshghi, P., Jenabzade, A. and Habibpanah, B. (2014) ‘A self-controlled comparative clinical trial to explore the eGectiveness of three topical hemostatic agents for stopping severe epistaxis in pediatrics with inherited coagulopathies’, Hematology, 19(6), 361-4, available: http://dx.doi.org/10.1179/1607845413y.0000000135.
Hosseinialhashemi, M., Jahangiri, R., Faramarzi, A., Asmarian, N., Sajedianfard, S., Kherad, M., Soltaniesmaeili, A. and Babaei, A. (2022) ‘Intranasal Topical Application of Tranexamic Acid in Atraumatic Anterior Epistaxis: A Double-Blind Randomized Clinical Trial’, Ann Emerg Med, 80(3), 182-188, available:http://dx.doi.org/10.1016/j.annemergmed.2022.04.010.
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Reuben, A., Appelboam, A., Stevens, K.N., Vickery, J., Ewings, P., Ingram, W., JeGery, A.N., Body, R., Hilton, M., Coppell, J., Wainman, B. and Barton, A. (2021) ‘The Use of Tranexamic Acid to Reduce the Need for Nasal Packing in Epistaxis (NoPAC): Randomized Controlled Trial’, Annals of Emergency Medicine, 77(6), 631-640, available: http://dx.doi.org/10.1016/j.annemergmed.2020.12.013.
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Whitworth, K., Johnson, J., Wisniewski, S. and Schrader, M. (2020) ‘Comparative EGectiveness of Topically Administered Tranexamic Acid Versus Topical Oxymetazoline Spray for Achieving Hemostasis in Epistaxis’, Journal of Emergency Medicine, 58(2), 211-216, available: http://dx.doi.org/10.1016/j.jemermed.2019.11.038.
World Health Organization (2024) Ageing and health, available: https://www.who.int/news- room/fact-sheets/detail/ageing-and-health [accessed 20. February 2024].
Zahed, R., Mousavi Jazayeri, M.H., Naderi, A., Naderpour, Z. and Saeedi, M. (2018) ‘Topical Tranexamic Acid Compared With Anterior Nasal Packing for Treatment of Epistaxis in Patients Taking Antiplatelet Drugs: Randomized Controlled Trial’, Acad Emerg Med, 25(3), 261-266, available: http://dx.doi.org/10.1111/acem.13345.
