Author: Jessica Bode, MD (EM Resident Physician, PGY-2, NUEM) // Edited by: Elizabeth Byrne, MD (EM Resident Physician, PGY-4 NUEM) // Expert Commentary: Ann Vertovec, MD
Citation: [Peer-Reviewed, Web Publication] Bode J , Byrne E (2016, December 6). TXA In Epistaxis [NUEM Blog. Expert Commentary By Vertovec A]. Retrieved from http://www.nuemblog.com/blog/txa-epistaxis
Overview
Sixty percent of the general population experiences a nosebleed at least once in their lifetime, making this a common emergency department (ED) presentation. Most cases occur before age 10 or between 45 and 65 years of age. The vast majority of epistaxis cases are anterior, with 90% of those occurring in Kiesselbach’s plexus located in the nasal septum. Usually the precipitating event is nasal trauma or irritation.
Typical management of anterior epistaxis in the ED involves employing non-invasive measures first such as having the patient hold firm pressure over the nasal septum for 10-15 minutes after taking care to blow out all clots. It’s unclear how often these measure alone are successful, but further management employs vasoconstrictor agents, cauterization, and nasal packing with ribbon gauze or nasal tampon. A simpler, more effective method could reduce the downsides of this approach which include prolonged length of stays, risk of infection, and significant patient discomfort.
Tranexamic Acid (TXA) is a synthetic analog of lysine that reversibly binds to plasminogen or plasmin, preventing plasmin from binding to and degrading fibrin and therefore preserving clot formation. It has roughly eight times the anti-fibrinolytic activity of an older analogue, ε-aminocaproic acid. TXA is available commercially in both a 100 mg/mL injectable solution, and an oral 650 mg tablet. Though the FDA-approved indications for TXA are limited to the treatment of hemophilia (injectable form) and menorrhagia (tablet form), it has been been gaining traction in the literature as a promising therapy for a variety of bleeding disorders - including epistaxis.
The Study
Zahed R et al. A new and rapid method for epistaxis treatment using injectable form of tranexamic acid topically: a randomized controlled trial. Am J Emerg Med. 2013 Sep;31(9):1389-92.
Study Design
Large city, single academic center randomized controlled trial
Population
Adult patients presenting to the ED with ongoing epistaxis, excluding patients with any of the following:
- major trauma
- posterior epistaxis
- known history of bleeding disorder such as thrombocytopenia, hemophilia, and platelet disorders
- international normalized ratio greater than 1.5
- shock
- visible bleeding vessel
Intervention Protocol
A total of 216 patients were randomized into one of two treatment arms, receiving either 1) 15cm cotton packing soaked in tranexamic acid (500mg in 5ml), removed after bleeding stopped or 2) usual anterior nasal packing (ANP) with cotton balls soaked in epinephrine (1:100,000) + lidocaine (2%) for 10 minutes and then re-packed with cotton pledgets covered with tetracycline that were removed after 3 days.
Outcome Measures
Outcomes included 1) time needed to arrest initial bleeding, 2) hours needed to stay in hospital, 3) any re-bleeding during 24 hours and 1 week later were recorded, and 4) the patient satisfaction at discharge time on a 0-10 scale.
Results
Interpretation
Notably, 71% of patients in the TXA group had cessation of bleeding in under 10 minutes compared to 31.2% of the ANP group. Length of stay was drastically reduced in the TXA group as well, with 95.3% of patients discharged in under two hours in contrast to 6.4% of the ANP group. Re-bleeding within the first 24 hours was reported less frequently in the TXA group (4.7% TXA vs. 12.8% ANP) as was re-bleeding within 1 week (2.8% TXA vs. 11% ANP). Finally, satisfaction rates were higher in the TX arm (8.5 ± 1.7) compared with the ANP group (4.4 ± 1.8) ( P < .001).
Overall, the authors concluded that topical application of injectable TXA was superior to usual anterior nasal packing in the ED setting. The study was a well-designed RCT that evaluated a practice-changing therapy that would serve to stop bleeding, increase ED throughput, and improve patient satisfaction. There were, however, significant gaps that will ultimately merit further investigation. For one, exclusion criteria prevented assessment of posterior epistaxis as well as patients with elevated INRs, known bleeding disorders or major trauma. There was also no grading of the epistaxis thus it is hard to know if topical TXA is superior than packing varying on the severity of bleeds. In addition, one of the design difficulties acknowledged by the authors is that this study was not truly blinded owing to the unique differences in color, consistency, and smell of the treatment options. Furthermore, there was also a marked imbalance in the two groups with more people in the TXA group having a history of epistaxis (58% vs 14%) that may falsely elevate the effectiveness of the intervention. And finally, others have pointed out that cotton pledgets soaked in tetracycline may represent a substandard competitor.
Conclusion
Injectable TXA applied topically for patients with anterior epistaxis is a promising new therapy that may ultimately become a mainstay of treatment, though it will require further research before it is more broadly generalizable to all-comers presenting to the ED with epistaxis.
Expert Commentary
Hi Jessica,
Thank you for your review of this study regarding TXA. TXA use in epistaxis sounds very promising, but its efficacy in a broader range of patients needs to be verified in larger studies. We have come a long way from the old days of petroleum jelly ribbon packing which was uncomfortable, time consuming and often less effective. Rapid Rhino, Merocel and similar products have really simplified nosebleed management but they are still uncomfortable, require oral antibiotics, and mandate close follow up for removal. In addition, they are associated with a risk of infection and even hypoxia in predisposed patients. I have occasionally used Gelfoam and Quick Clot on patients with some success but the TXA results in the article are even more encouraging with shorter ED stay and less re-bleeding. I look forward to further studies of TXA for epistaxis, in particular with patients on blood thinners who often have significant nosebleeds and are prone to re-bleeding.
By the way, my three favorite mainstays for treating nosebleeds are initial use of a nasal clip, topical cocaine (the only topical anesthetic that is also a vasoconstrictor), and use of suction to remove clots and isolate the bleeding source.
Ann Vertovec, MD
Attending Emergency Physician, Northwestern Lake Forest Hospital
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References
- Kucik CJ, Clenney T. Management of epistaxis. Am Fam Physician 2005; 71:305.
- Alvi A, Joyner-Triplett N. Acute epistaxis. How to spot the source and stop the flow. Postgrad Med 1996; 99:83.
- Aeumjaturapat S., Supanakorn S., and Cutchavaree A.: Toxic shock syndrome after anterior-posterior nasal packing. J Med Assoc Thai 2001; 84: pp. 453-458
- Nilsson IM, “Clinical Pharmacology of Aminocaproic and Tranexamic Acids,” J Clin Pathol Suppl, 1980, 14:41-7.
- David Clinkard and David Barbic (2016). Tranexamic Acid for Epistaxis–A Promising Treatment That Deserves Further Study. CJEM, 18, pp 72-73. doi:10.1017/cem.2015.55.
- Zahed R et al. A new and rapid method for epistaxis treatment using injectable form of tranexamic acid topically: a randomized controlled trial. Am J Emerg Med. 2013 Sep;31(9):1389-92.