TXA: Still a Gold Medal for Stopping the Bleed?

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Ruben Santiago
Ruben Santiago
Emergency Medicine Pharmacist and medication hustler at a level I trauma center in Miami, FL. Interests include trauma, toxicology, and infectious diseases.

The Pre-brief

  • Approximately one out of every 200 visits to the emergency department (ED) in the United States is due to epistaxis and about 60% of the world’s population will experience epistaxis in their lifetime
  • Tranexamic acid (TXA) is an antifibrinolytic agent that is used for multiple etiologies of hemorrhage, most famous (or infamous) for trauma, and may also be used in the management of postpartum hemorrhage, gastrointestinal bleeding, hemoptysis, dental bleeds, post-tonsillectomy bleeds, topical bleeds… chances are if its bleeding, someone probably gave TXA for it
  • Topical TXA is a noninvasive, nonpainful, low-cost treatment that may also be used in the management of epistaxis
  • When administered topically, there is a low rate of adverse events due to minimal systemic absorption
  • Small, single-center studies initially spurred interest in the use of topical TXA for epistaxis; however, a larger more recent study has challenged its overall acceptance for this condition

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. 

The Debrief

  • TXA is an antifibrinolytic agent that is used for multiple etiologies of hemorrhage
  • Small studies and systematic reviews support the use of TXA as a viable option for acute epistaxis
  • Although the largest trial demonstrates similar results versus placebo, TXA may still be considered as it is a low cost, noninvasive, nonpainful treatment option with a low adverse event rate
  • When administered topically, the IV formulation of TXA 500 mg/5 mL may be utilized and soaked onto a cotton pledget and placed in the bleeding nostril

References

  1. Gottlieb M, DeMott J, Peska G. Topical tranexamic acid for the treatment of acute epistaxis: a systematic review and meta-analysis. Ann Pharmacother. 2019; 53(6): 652 – 657. 
  2. Zahed R, Moharamzadeh P, AlizadehArasi S, Ghasemi A, Saeedi M. A new and rapid method for epistaxis treatment using injectable form of tranexamic acid topically: a randomized control trial. Am J Emerg Med. 2013; 31: 1389 – 1392. 
  3. Zahed R, Jazayeri M, Naderi A, Naderpour Z, Saeedi M. Topical tranexamic acid compared with anterior nasal packing for treatment of epistaxis in patients taking antiplatelet drugs: randomized controlled trial. Acad Emerg Med. 2018; 25(3): 261 – 266. 
  4. Birmingham A, Mah N, Ran R, Hansen M. Topical tranexamic acid for the treatment of acute epistaxis in the emergency department. Am J Emerg Med. 2018; 36(7): 1242 – 1245. 
  5. Dunn C, Goa K. Tranexamic acid: a review of its use in surgery and other indications. Drugs. 1999: 57(6): 1005 – 1032. 
  6. Cap AP, et. al. Tranexamic acid for trauma patients: a critical review of the literature. J Trauma. 2011; 71: S9 – S14.
  7. Reed R, Woolley T. Uses of tranexamic acid. Continuing Education in Anaesthesia Critical Care and Pain. 2015; 15(1): 32 – 37. 
  8. Wu T, et. al. Computational model of tranexamic acid on urokinase mediated fibrinolysis. PLoS ONE. 2020; 15(5): 1 – 11. 
  9. 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. 2020;9(1):e6.
  10. Whitworth K, Johnson J, Wisniewski S, Schrader M. Comparative effectiveness of topically administered tranexamic acid versus topical oxymetazoline spray for achieving hemostasis in epistaxis. J Emerg Med. 2020; 58(2): 211 – 216. 
  11. Akkan S, Corbaciogiu S, Aytar H, Emektar E, Dagar S, Cevik Y. Evaluating effectiveness of nasal compression with tranexamic acid compared with simple nasal compression and merocele packing: a randomized controlled trial. Ann Emerg Med. 2019; 74: 72 – 78. 
  12. Reuben A,  Appleboam A, Stevens K, Vickery J, Ewings P, Ingram W, et. al. The use of tranexamic acid to reduce the need for nasal packing in epistaxis (NoPAC): randomized controlled trial. Ann Emerg Med. 2021; 1 – 10.

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