Archives of Academic Emergency Medicine. 2021; 9(1): e6 https://doi.org/10.22037/aaem.v9i1.875 OR I G I N A L RE S E A RC H Topical Tranexamic Acid versus Phenylephrine-lidocaine for the Treatment of Anterior Epistaxis in Patients Taking Aspirin or Clopidogrel; a Randomized Clinical Trial Keyvan Amini1, AmirAhmad Arabzadeh2∗, Sevda Jahed3, Payman Amini3 1. Department of Emergency Medicine, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran. 2. Department of surgery, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran. 3. School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran. Received: September 2020; Accepted: October 2020; Published online: 19 November 2020 Abstract: Introduction: Epistaxis is one of the most prevalent complaints in the emergency department (ED), especially in patients who take antiplatelet agents. This study aimed to compare the effect of topical use of tranexamic acid (TXA) with phenylephrine-lidocaine anterior nasal packing (PANP) in controlling epistaxis of patients who take aspirin or clopidogrel. Methods: This prospective, double-blind, parallel-group, randomized clinical trial was conducted to compare the effect of topical use of intravenous (IV ) TXA compared with PANP on controlling anterior epistaxis in patients who take aspirin or clopidogrel. Results: One hundred patients with the mean age of 59.24 ± 7.75 (45 – 75) years were studied (52% male). Two groups were similar in terms of age (p=0.81) and sex (p=0.23) distribution, diabetes mellitus (p=0.54), and hypertension (p = 0.037). The mean time to stop bleed- ing was 6.70 ± 2.35 minutes in the TXA group and 11.50±3.64 minutes in the PANP group (p=0.002). Bleeding recurrence occurred in 3 (6%) cases of the TXA group and 10 (20%) cases of the PANP group (p =0.03). Time to discharge from ED in the TXA group was significantly lower than the PANP group (p<0.001). The absolute risk reduction (ARR), relative risk reduction, and number needed to harm of treatment with TXA for anterior nasal bleeding were 14.00% (95%CI: 1.11 – 26.89), 17.50% (95%CI: 0.60 - 37.27), and 7.14 (95%CI: 3.71 -90.43), respectively. Conclusion: Topical TXA is an appropriate treatment option in bleeding cessation, and reducing re-bleeding and duration of hospital stay in patients with epistaxis who take antiplatelet agents. Keywords: Tranexamic Acid; phenylephrine, lidocaine drug combination; Epistaxis; Aspirin; Clopidogrel; Emergency Medical Services Cite this article as: Amini K, Arabzadeh A, Jahed S, Amini P. Topical Tranexamic Acid versus Phenylephrine-lidocaine for the Treatment of Anterior Epistaxis in Patients Taking Aspirin or Clopidogrel; a Randomized Clinical Trial. Arch Acad Emerg Med. 2021; 9(1): e6. 1. Introduction Epistaxis is described as bleeding from the nostrils, inner part of the nasal cavity, or nasopharynx, and is one of the most common complaints among patients referring to the emergency department (ED) (1). The lifetime prevalence of epistaxis is about 60% and up to 6% will need medical care (2). Global estimations show that nosebleed mostly occurs in children under 10 and elderly over 60 years old, which results in the bimodal age distribution (3). About 90% of nosebleeds ∗Corresponding Author: AmirAhmad Arabzadeh; Department of surgery, Fatemi Hospital, Ardabil, Iran. Email: amir.arabzadeh@arums.ac.ir, amir_medico@yahoo.com Fax number: +984533249947, Tel: +984533249947, ORCID: https://orcid.org/0000-0001-9594-5522. originate from Kiesselbach’s plexus in the anterior nasal sep- tum, while the remaining 10% occurs in the posterior nasal septum or the lateral wall of the nasal cavity (4). Many lo- cal and systemic conditions such as traumas (physical or medication-induced mucosal traumas), decreased nasal mu- cosa moisture, septal perforations, viral or bacterial rhinosi- nusitis, neoplasms, coagulation disorders, and some drugs such as anticoagulant or antiplatelet agents may cause epis- taxis (3). Although epistaxis is typically self-limiting; it can be life-threatening in elderly patients, especially those who have underlying diseases and take antiplatelet medications such as aspirin or clopidogrel (5). Various treatment strate- gies, from compression therapy to nasal packing, are avail- able in ED to control nosebleed (6). Some studies suggest us- ing tranexamic acid (TXA), an antifibrinolytic agent, in oral, This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem K. Amini et al. 2 intravenous (IV ), or topical forms to control epistaxis; but the clinical evidence of its use is limited, especially in patients who receive antiplatelet aggregation agents (7-9). Since us- ing antiplatelet drugs is common in older ages, it is of great importance to appropriately manage this group of patients. This study aimed to compare the effect of topical use of intra- venous (IV ) TXA with phenylephrine-lidocaine anterior nasal packing (PANP) in controlling epistaxis of patients who take aspirin or clopidogrel. 2. Methods 2.1. Study design and setting This prospective, double-blind, parallel-group, randomized clinical trial was conducted in the ED of the Fatemi Hospital, affiliated to Ardabil University of Medical Sciences (ARUMS), to compare the effect of topical use of TXA (intravenous (IV ) form) with PANP, in controlling anterior epistaxis. This study was approved by the Ethics Committee of ARUMS (ethics code: IR.ARUMS.REC.1398.249) and was registered on the Iranian Registry of Clinical Trials (IRCT) with the number IRCT20191008045031N1. Before beginning the study, patients were assured that they were free to participate or not, they would not be charged any additional fees for participating, and the researchers adhered to ethical principles and their personal information is com- pletely confidential and would not be published anywhere. The written informed consent was obtained from all partici- pants before the study. 2.2. Participants All patients who referred to ED with an episode of epistaxis and were under treatment with antiplatelet drugs (aspirin, clopidogrel, or both) were enrolled in this study. Patients not willing to participate in the study and those with mul- tiple trauma, hereditary hemorrhagic or platelet disorders, hemophilia, renal dysfunction, or obvious bleeding from other parts of the body were excluded. 2.3. Intervention After diagnosis confirmation by an emergency medicine spe- cialist in the ED, eligible patients were randomly allocated to either receive a single topical application of 1-gram TXA IV form (Tranexip (B: 215)) or PANP (Nasophrin (lot: 902872)) using block randomization method. The triage nurse who was blinded to the intervention, delivered prepacked se- quentially numbered boxes, which were not accessible to other ED staff and contained intervention material, in the procedure room. The TXA group received a wad of cotton steeped in the injectable form of TXA (500 mg in 5 mL), which was lodged into the bleeding nostril. The PANP group re- ceived a wad of cotton steeped in phenylephrine (1:100,000) + lidocaine (2%) lodged into the bleeding nostril and re- mained for 10 minutes. Following bleeding cessation, tetra- cycline ointment-soaked PANP was inserted and left in place for 3 days for both groups. To assess intervention outcomes in both groups, a blinded attending emergency medicine specialist confirmed bleeding cessation and in case of per- sistent bleeding despite initial intervention, an appropriate second-line treatment e.g., cautery was considered. 2.4. Outcome The primary outcome was bleeding cessation time defined as the time it took the treatment to stop bleeding. The sec- ondary outcomes were: (a) bleeding recurrence defined as re-bleeding within 72 hours after the initial bleeding episode, (b) the length of hospital stay, and (c) the relationship be- tween bleeding recurrence with sex, hypertension (HTN), and diabetes mellitus (DM) in both treatment arms. Patient’s demographic information such as age, sex, duration of as- pirin or clopidogrel administration and their dosage were recorded in researcher-developed questionnaires that were filled out by the patients. 2.5. Randomization The random allocation sequence was generated by our triage nurse, using SPSS software for windows version 16, which was stratified by the center. All patients who met the inclu- sion criteria were randomly allocated to either the TXA group or the PANP group using a random sampling method. Se- quentially numbered boxes containing intervention medica- tions and materials were previously prepared and our nurse used a random allocation sequence to allocate a treatment to each patient. The boxes were completely identical in ap- pearance, size, and weight and were delivered sequentially to the medical intern. The triage nurse was blinded to the in- tervention and the contents of the boxes. Because of obvious differences in color and smell of the two medications used for our trial, the medical intern who performed the intervention was not blinded to the intervention. However, the attending emergency medicine specialist who evaluated the treatment outcomes and confirmed the bleeding cessation and bleed- ing recurrence within 72 hours was completely blinded to the intervention. The person who statistically analyzed the data was also blinded to the group assignment. 2.6. Statistical analysis Based on the data extracted from a previous similar trial, con- sidering the power of 90%, first type error of 0.5%, efficacy in the group p1 = 28.3, and p2 = 66.7%, the sample size was de- termined as 40 per group using the sample size formula for the intervention. We assigned the sample size of 50 people to each group considering the possibility of sample drop out. All data were analyzed using Statistical Package for the So- This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 3 Archives of Academic Emergency Medicine. 2021; 9(1): e6 Figure 1: Patient allocation flowchart. PANP: phenylephrine/lidocaine soaked anterior nasal packing; TXA: tranexamic acid. cial Sciences (SPSS) version16. Descriptive statistical meth- ods (frequency, percentage, mean ± standard deviation [SD]) were used for the presentation of the findings. Independent T-test was used to compare the quantitative findings and Chi- square test was used to compare the qualitative findings. P- values of less than 0.05 were considered significant. The absolute risk reduction, relative risk reduction, and number needed to harm (uncontrolled bleeding) of treat- ment with TXA for anterior nasal bleeding were calculated and reported with 95% confidence interval (CI). 3. Results 3.1. Baseline characteristics of the studied cased One hundred patients with the mean age of 59.24 ± 7.75 (45- 75) years were studied (52% male). Figure 1 shows the allo- cation flowchart of the study. Baseline characteristics of the studied cases were compared between groups in table 1. The two groups were similar in terms of the age (p = 0.81) and sex (p = 0.23) distribution, diabetes mellitus (p = 0.54), hyperten- sion (p= 0.037), and history of bleeding (p = 0.001). This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem K. Amini et al. 4 3.2. Treatment outcomes Table 2 compares the treatment outcomes between the groups. The mean time to stop bleeding was 6.70 ± 2.35 minutes in the TXA group and 11.50 ± 3.64 minutes in the PANP group (p=0.002 ). Bleeding recurrence occurred in 3 (6%) of the cases who were treated with TXA and 10 (20%) cases treated with PANP (p=0.03). Time to discharge from ED in the TXA group was significantly lower than the PANP group (p<0.001). Patients with a history of HTN had signifi- cantly higher rates of bleeding recurrence in the PANP group (p= 0.001). The absolute risk reduction (ARR), relative risk reduction, and number needed to harm of treatment with TXA for ante- rior nasal bleeding were 14.00% (95%CI: 1.11 – 26.89), 17.50% (95%CI: 0.60 - 37.27), and 7.14 (95%CI: 3.71 -90.43), respec- tively. 4. Discussion The findings of this study indicate that the use of TXA for management of epistaxis is associated with faster bleeding cessation, lower rates of re-bleeding, and a shorter length of hospital stay compared to PANP. Treatment with TXA had 17.5% lower risk of rebleeding. Number needed to harm of treatment with TXA was 7.1, which means that about 7 pa- tients need to be treated with TXA in order for one case to have uncontrolled bleeding. Local compression is the first step in management of epis- taxis with anterior circulation origin (10). The next steps may include the application of a cotton swab soaked in vasocon- strictors, cauterization, and nasal packing. Finally, nasal en- doscopy may be considered to find underlying pathogene- sis, in cases with recurrent epistaxis (5, 10). Current clini- cal guidelines suggest using resorbable packing for patients with bleeding disorders or those receiving antiplatelet or an- ticoagulation agents (10). Packing strategies have shown to lessen the length of hospital stay compared to non-packing ways such as cauterization, embolization, and ligation (11). Tranexamic acid is a synthetic analogue of lysine amino acid, which binds to plasminogen and plasmin, thereby inhibiting their ability to bind to residual lysine in fibrin, thus prevent- ing fibrinolysis. It is used in heavy menstrual bleedings, post- partum hemorrhage, bleedings following dental procedures, and hematologic disorders (12). This treatment is readily available, inexpensive, and easy to apply (12, 13). Several studies have investigated its effect on controlling epistaxis in patients taking or not taking antiplatelet drugs (9). Interest- ingly, it has been beneficial in nebulized and atomized in- tranasal forms in patients with difficult-to-control epistaxis (14, 15). Literature review on TXA efficacy demonstrates its benefits in reducing recurrent bleeding and duration of hos- pital stay, as well as higher patient satisfaction. Similar to our findings, Zahed et al. showed that TXA is sig- nificantly more efficient in bleeding cessation within 10 min- utes of application, compared to PANP, in patients receiv- ing antiplatelet medications such as aspirin and clopidogrel. Moreover, TXA reduced re-bleeding within one week of the first episode and the length of hospital stay (7). In a study by Saeedi et al., 68% of people treated with TXA achieved hemostasis in 5-10 minutes, whereas this measure was 15-20 minutes in patients treated with anterior nasal tampon. They also reported lower re-bleeding rates and hospital length of stay in patients receiving TXA, compared to anterior tam- pon, which are consistent with our findings (16). Atabaki et al. made a comparison between phenylephrine and TXA in terms of achieving hemostasis after 10 minutes of applica- tion in patients with nosebleed, and observed a significant difference between two groups (17). The results of another study by Zahed et al., comparing topical use of the injectable form of TXA with ANP with tetracycline ointment, demon- strated that TXA was more efficient in stopping initial bleed- ing, which led to shorter hospital stay length, but it showed no superiority in reducing bleeding recurrence (9). Compari- son of the effect of topical application of IV form of TXA with topical oxymetazoline spray, a vasoconstrictor medication, revealed the significant advantage of using TXA to control bleeding (18). A retrospective study of adult patients with epistaxis who were admitted to a general hospital showed that using TXA had considerable results in reducing bleeding. The results of this study specified diabetes and hypertension as strong pre- dictors of re-admission, which is in agreement with our find- ings (19). A number of studies have investigated the effect of TXA on some hematologic disorders (20, 21). The results of a placebo-controlled cross-over trial in patients with heredi- tary hemorrhagic telangiectasia complaining of epistaxis re- vealed that the administration of TXA significantly reduces the mean duration of epistaxis per month but not the me- dian number of epistaxis episodes per month (20). A similar trial by Geisthoff et al. also suggests that the administration of one gram of TXA, three times daily for three months can reduce epistaxis score by 54% compared to the placebo in pa- tients with hereditary hemorrhagic telangiectasia (21). Among anticoagulant medications, TXA was considered an effective management option in a patient with underlying atrial fibrillation, receiving rivaroxaban (a factor X inhibitor used for stroke prophylaxis) who was referred to ED due to epistaxis (22). In contrast to our findings, some studies found little or no benefits in using TXA for treating epistaxis. The re- sults of one study, comparing TXA gel with placebo, showed no significant differences in time to control bleeding and its recurrence (23). Using oral TXA for 10 days as adjunct ther- apy revealed no superiority to placebo regarding re-bleeding This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 5 Archives of Academic Emergency Medicine. 2021; 9(1): e6 Table 1: Screening performance characteristics of rapid emergency medicine score (REMS) and rapid acute physiology score (RAPS) in pre- diction of mortality and poor outcome Variables Treatments P value TXA (n = 50) PANP (n = 50) Age (year) 45 - 55 17 (34.0) 18 (36.0) 55 - 65 27 (54.0) 25 (50.0) 0.91 ≥ 65 6 (12.0) 7 (14.0) Sex Male 29 (58.0) 23 (46.0) 0.2 Female 21 (42.0) 27 (54.0) Diabetes mellitus Yes 7 (14.0) 5 (10.0) 0.54 No 43 (86.0) 45 (90.0) Hypertension Yes 5 (10.0) 13 (26.0) 0.037 No 45 (90.0) 37 (74.0) Data are presented as mean ± standard deviation (SD) or number (%). TXA: tranexamic acid; PANP: phenylephrine/lidocaine soaked anterior nasal packing. Table 2: Overall performance of rapid emergency medicine score (REMS) and rapid acute physiology score (RAPS) in prediction of in-hospital mortality and poor outcome Variables Treatments P value TXA (n = 50) PANP (n = 50) Successful bleeding control Number (%) 47(94.0) 40 (80.0) 0.037 Bleeding Cessation Time (minutes) < 5 10 (20.0) 1 (2.0) 5 – 10 35 (70.0) 6 (12.0) 0.001 10 - 15 5 (10.0) 22 (4.0) ≥ 15 0 (0.0) 21 (42.0) Re-bleeding in 72 hours N (%) 3 (6.0) 10 (20.0) 0.03 Duration of hospital stay (Hours) <1 19 (38.0) 3 (6.0) 1 – 2 26 (52.0) 5 (10.0) <0.001 2 -4 3 (6.0) 24 (48.0) >4 2 (4.0) 18 (36.0) Data are presented as mean ± standard deviation (SD) or number (%). TXA: tranexamic acid; PANP: phenylephrine/lidocaine soaked anterior nasal packing and its severity within 10 days of initial epistaxis (24). In the survey of Birmingham et al., topical TXA was not beneficial for reducing ED length of stay; however, it was associated with a significant reduction in otolaryngologist consults and nasal packing rates in management of acute epistaxis (25). Topical use of the IV form of TXA seems to provide a better treatment option for anterior epistaxis compared with PANP in patients, taking antiplatelet drugs. The advantages of topi- cal TXA treatment demonstrated in our study included quick bleeding cessation, and reducing re-bleeding and duration of hospital stay in patients. The technique is also relatively sim- ple and is easy to teach and learn. 5. Limitation The main limitation of this study was the small sample size. Another limitation was the lack of an objective measurement index for the bleeding cessation in patients with epistaxis; however, we tried to reduce the effect of this limitation by asking for the opinions of an emergency medicine attend for confirming bleeding cessation. 6. Conclusion Topical TXA is an appropriate treatment option for cessation of bleeding, and reducing re-bleeding and duration of hospi- tal stay in patients with epistaxis who take antiplatelet agents. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem K. Amini et al. 6 7. Declaration 7.1. Acknowledgements The authors would like to thank Ardabil University of Medi- cal Sciences, Ardabil, Iran for financial support, cooperation, and assistance throughout the study. 7.2. Author contribution K.A. and A.A.; Designed and performed experiments, ana- lyzed data, and wrote the paper. K.A. and S.J.; Performed ex- periments. P.A.; Performed bioinformatics analyses. K.A. and A.A.; Supervised the research. 7.3. Funding/Support None. 7.4. Conflict of interest The authors declare no conflict of interest. References 1. Viehweg TL, Roberson JB, Hudson J. Epistaxis: diagnosis and treatment. Journal of oral and maxillofacial surgery. 2006;64(3):511-8. 2. Chaaban MR, Zhang D, Resto V, Goodwin JS. Demo- graphic, seasonal, and geographic differences in emer- gency department visits for epistaxis. Otolaryngology– Head and Neck Surgery. 2017;156(1):81-6. 3. Bell MD G. Management of Epistaxis. 2016. 4. Tabassom A, Cho JJ. Epistaxis (nose bleed). StatPearls [In- ternet]. 2020. 5. Svider P, Arianpour K, Mutchnick S. Management of epis- taxis in children and adolescents: avoiding a chaotic ap- proach. Pediatric Clinics. 2018;65(3):607-21. 6. Wojak JC, editor Endovascular Treatment of Epistaxis. Seminars in Interventional Radiology; 2020: Thieme Medical Publishers. 7. Runyon MS. Topical tranexamic acid for epistaxis in pa- tients on antiplatelet drugs: a new use for an old drug. Academic Emergency Medicine. 2018;25(3):360-1. 8. Joseph J, Martinez-Devesa P, Bellorini J, Burton MJ. Tranexamic acid for patients with nasal haemorrhage (epistaxis). Cochrane Database of Systematic Reviews. 2018(12). 9. Zahed R, Mousavi Jazayeri MH, Naderi A, Naderpour Z, Saeedi M. Topical tranexamic acid compared with ante- rior nasal packing for treatment of epistaxis in patients taking antiplatelet drugs: randomized controlled trial. Academic Emergency Medicine. 2018;25(3):261-6. 10. Tunkel DE, Anne S, Payne SC, Ishman SL, Rosenfeld RM, Abramson PJ, et al. Clinical practice guideline: nosebleed (epistaxis). Otolaryngology–Head and Neck Surgery. 2020;162(1_suppl):S1-S38. 11. Zhou AH, Chung SY, Sylvester MJ, Zaki M, Svider PS, Hsueh WD, et al. To pack or not to pack: inpatient man- agement of epistaxis in the elderly. American journal of rhinology & allergy. 2018;32(6):539-45. 12. Sethi RK, Kozin ED, Abt NB, Bergmark R, Gray ST. Treatment disparities in the management of epistaxis in United States emergency departments. The Laryngo- scope. 2018;128(2):356-62. 13. Timp JF, Braekkan SK, Lijfering WM, van Hylckama Vlieg A, Hansen J-B, Rosendaal FR, et al. Prediction of recur- rent venous thrombosis in all patients with a first ve- nous thrombotic event: The Leiden Thrombosis Recur- rence Risk Prediction model (L-TRRiP). PLoS medicine. 2019;16(10):e1002883. 14. McGrath ER, Go AS, Chang Y, Borowsky LH, Fang MC, Reynolds K, et al. Use of oral anticoagulant therapy in older adults with atrial fibrillation after acute is- chemic stroke. Journal of the American Geriatrics Soci- ety. 2017;65(2):241-8. 15. Cai J, Ribkoff J, Olson S, Raghunathan V, Al-Samkari H, DeLoughery TG, et al. The many roles of tranexamic acid: An overview of the clinical indications for TXA in medical and surgical patients. European journal of haematology. 2020;104(2):79-87. 16. Abootalebi Ghahnavieh A, Tashayoie A, Nasr Esfahani M, Golshani K. Comparative Study of the Efficacy of Top- ical Tranexamic Acid with Nasal Tampon in Manage- ment of Epistaxis: A Randomized Clinical Trial. Scien- tific Journal of Kurdistan University of Medical Sciences. 2020;25(4):140-9. 17. Atabaki P, Soheili A, Aribi MS, Samarei R, Mehryar HR. A comparative study on the effect of topical phenylephrine with topical tranexamic acid in management of epistaxis. The J Urmia Nurs Midwifery Fac. 2017;15(7):488-96. 18. Whitworth K, Johnson J, Wisniewski S, Schrader M. Comparative Effectiveness of Topically Administered Tranexamic Acid Versus Topical Oxymetazoline Spray for Achieving Hemostasis in Epistaxis. The Journal of emer- gency medicine. 2020;58(2):211-6. 19. Jervis S, Saunders T, Belcher J, Skinner D. Evaluating three hundred and fifty-two admissions and predictors of re-admissions for epistaxis–is it time to re-evaluate tranexamic acid in epistaxis? Clinical Otolaryngology. 2017;42(2):439-42. 20. Gaillard S, Dupuis-Girod S, Boutitie F, Rivière S, Morinière S, Hatron PY, et al. Tranexamic acid for epistaxis in hereditary hemorrhagic telangiectasia patients: a European cross-over controlled trial in a rare disease. Journal of Thrombosis and Haemostasis. 2014;12(9):1494-502. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 7 Archives of Academic Emergency Medicine. 2021; 9(1): e6 21. Geisthoff UW, Seyfert UT, Kübler M, Bieg B, Plinkert PK, König J. Treatment of epistaxis in hereditary hem- orrhagic telangiectasia with tranexamic acid-a double- blind placebo-controlled cross-over phase IIIB study. Thrombosis Research. 2014;134(3):565-71. 22. Utkewicz MD, Brunetti L, Awad NI. Epistaxis compli- cated by rivaroxaban managed with topical tranexamic acid. The American journal of emergency medicine. 2015;33(9):1329. e5-. e7. 23. Tibbelin A, Aust R, Bende M, Holgersson M, Petruson B, Rundcrantz H, et al. Effect of local tranexamic acid gel in the treatment of epistaxis. ORL. 1995;57(4):207-9. 24. White A, O’reilly B. Oral tranexamic acid in the manage- ment of epistaxis. Clinical Otolaryngology & Allied Sci- ences. 1988;13(1):11-6. 25. Birmingham AR, Mah ND, Ran R, Hansen M. Topical tranexamic acid for the treatment of acute epistaxis in the emergency department. The American journal of emergency medicine. 2018;36(7):1242-5. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem Introduction Methods Results Discussion Limitation Conclusion Declaration References