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Date: March 6th, 2018
Reference: Zahed et al. Topical Tranexamic Acid Compared With Anterior Nasal Packing for Treatment of Epistaxis in Patients Taking Antiplatelet Drugs: Randomized Controlled Trial. AEM March 2018.
Guest Skeptic: Dr. Justin Morgenstern is an emergency physician and the Director of Simulation Education at Markham Stouffville Hospital in Ontario. He is the creator of the excellent #FOAMed project called First10EM.com
Case: A 77-year-old woman with known coronary artery disease is on clopidogrel and aspirin because of a stent placed four month ago. She has epistaxis that has not resolved despite twenty minutes of well applied anterior pressure. As you are preparing your equipment, she tells you that this is her third episode of epistaxis, and she is really hoping there is some alternative to the anterior packing she had the last two times.
Background: About 60% of the population will experience a nose bleed. There is a bimodal distribution (<10yrs and > 60yrs) with the majority of refractory hemorrhages are seen in the elderly. In more than two-thirds of the time no cause is identified
An anterior bleed is much more common than a posterior bleed and often occurs at the Kiesselbach’s Plexus. It is usually easy to diagnose anterior versus posterior epistaxis with direct visualization.
There are many causes of epistaxis and a variety of treatments. For the adult management of epistaxis there is something called the Dundee Protocol. We will put a link in the show notes to the protocol.
The American College of Chest Physicians published some evidence-based recommendations in 2012 on anticoagulation therapy [1]. We will summarize some of the recommendations for emergent anticoagulation reversal in the emergency department in the show notes.
TXA is a synthetic derivative of lysine that inhibits fibrinolysis and thus stabilizing clots that are formed. TXA has been widely used in elective surgical cases and has shown decreased need for blood transfusion and reduction in mortality. It made sense to look at it for the treatment of epistaxis.
Zahed et al did a randomized control trial (RCT) in 2013 on using TXA for the treatment of anterior epistaxis [2]. They excluded patients on anticoagulation medications but not those taking antiplatelet drugs
We reviewed that RCT on SGEM#53 and the bottom line was that for patients with anterior epistaxis, consider soaking the packing in TXA to stop the bleeding and get them home sooner.
The SGEM also reviewed the use of TXA in the CRASH-2 on SGEM#80 with Anand Swaminathan. And coming up soon, we have an episode reviewing the use of TXA in post-partum hemorrhage.
Clinical Question: In patients taking antiplatelet medication who present to the emergency department with epistaxis, does topical tranexamic acid result in less bleeding than standard anterior nasal packing?
Reference: Zahed et al. Topical Tranexamic Acid Compared With Anterior Nasal Packing for Treatment of Epistaxis in Patients Taking Antiplatelet Drugs: Randomized Controlled Trial. AEM March 2018.
- Population: Patients taking antiplatelet medications (aspirin, clopidogrel, or both) with epistaxis continuing after 20 minutes of pressure.
- Exclusions: Traumatic epistaxis, anticoagulant use, inherited bleeding disorders, inherited platelet disorders, INR > 1.5, shock, a bleeding visible vessel, renal disease, or lack of consent.
- Intervention: Anterior packing with a 15cm cotton pledget soaked in 500mg of tranexamic acid and left in place until bleeding stopped.
- Comparison: Anterior packing with a cotton pledget soaked in epinephrine (1:100,000) and lidocaine (2%) and left in place for 10 minutes. It was then removed and a standard anterior nasal pack was placed for three days.
- Outcome:
- Primary Outcome: Bleeding at 10 minutes
- Secondary Outcomes:
- Epistaxis recurrence at 24 hours and 7 days after treatment
- Emergency department length of stay (LOS)
- Patient satisfaction on a 0–10 numeric scale
Authors’ Conclusions: “In our study population, epistaxis treatment with topical application of TXA resulted in faster bleeding cessation, less re-bleeding at 1week, shorter ED LOS, and higher patient satisfaction as compared with ANP”.
Quality Checklist for Randomized Clinical Trials:
- The study population included or focused on those in the emergency department. Yes
- The patients were adequately randomized. Yes
- The randomization process was concealed. Yes
- The patients were analyzed in the groups to which they were randomized. Yes
- The study patients were recruited consecutively (i.e. no selection bias). No. There were a high number of exclusion due to lack of consent.
- The patients in both groups were similar with respect to prognostic factors. Yes
- All participants (patients, clinicians, outcome assessors) were unaware of group allocation. No
- All groups were treated equally except for the intervention. Unsure
- Follow-up was complete (i.e. at least 80% for both groups). Yes
- All patient-important outcomes were considered. Yes
- The treatment effect was large enough and precise enough to be clinically significant. Yes
Key Results: They randomized 124 patients in this trial with a median age of about 60 years with slightly more men than women included in the study.
More patients had their epistaxis stopped in 10 minutes when treated with TXA
- Primary Outcome: Bleeding stopped at 10 minutes in 73% of the TXA group and 29% of the standard packing group (absolute difference 44%; 95% confidence interval 26-57%; p<0.01) NNT 2
- Secondary Outcomes:
- 24 Hour Re-Bleeding: 5% with TXA vs. 10% control (p=0.30)
- 1-Week Re-Bleeding: 5% with TXA vs. 21% control (p=0.007)
- Emergency Department Length of Stay: 97% of TXA group discharged within two hours vs. 13% of controls (p<0.001)
- Patient Satisfaction: 9/10 with TXA vs. 4/10 with control (p<0.001)
- Adverse Events: No difference in serious adverse events.
1) Bias: There may have been selection bias introduced into the study. Of the 384 patients approached, 92 were excluded due to failure to provide consent. It is unclear how many patients were screened had their epistaxis resolved with the initial 20 minutes of pressure.
Another possible source of bias in this study is the lack of blinding. They said blinding was not possible due to the different number of pledgets required for anterior nose packing and the differences in the colour, smell and consistency of the medications used. However, the outcome assessors were blinded to group allocation.
2) Strawman Comparison: This study used bleeding stopped at ten minutes as the primary outcome. Standard anterior packing is not really supposed to stop bleeding at ten minutes and requires time to develop a stable pack. Would a 24 or 48-hour outcome have been a fairer comparison? However, when looking at the secondary outcome of 24 hours or one-week the TXA was still superior to standard care.
3) Length of Stay (LOS): The LOS times were presented just as the percentage left by two hours. However, it is difficult to determine if the difference is important. If most people in the TXA group left the department after one hour and 55 minutes, and the control group left at two hours and 5 minutes, this may not be an important difference. What was the actually difference in length of stay?
4) Who was Doing the Packing: Technique is probably more important in the outcomes after anterior packing than it is in using topical TXA. In this study, procedures were primarily done by trainees (PGY2s and PGY3s). That could impact the generalizability of the results to more experienced providers?
5) Other Treatment Options: The study looked at anterior nasal packing with cotton pledget. Frequently in epistaxis, multiple treatment options are used. Other options include cautery, epinephrine and commercial packing devices. These other treatment options were not commented upon in the paper.
Comment on Authors’ Conclusion Compared to SGEM Conclusion: We generally agree with the authors conclusions.
SGEM Bottom Line: Despite some limitations in this un-blinded trial, topical tranexamic acid appears to improve some patient important outcomes in patients who are taking antiplatelet medications who present with epistaxis.
Case Resolution: You discuss this trial on topical TXA with your patient, and she jumps at the alternative. After ten minutes the bleeding has stopped. You call her a week later to follow-up, and she is thrilled that the bleeding didn’t re-occur, and she didn’t have to spend multiple days with an anterior pack in place.
Dr. Justin Morgenstern
Clinical Application: Using topical tranexamic acid for epistaxis in the context of antiplatelet drug use seems to result in faster bleeding cessation, less re-bleeding at one week, and higher patient satisfaction. However, I would like to know if we always wait for the initial trial of 20 minutes of pressure, or are there patients who may benefit from starting TXA immediately? My personal practice is to use epinephrine, lidocaine, and TXA on all patients who are still bleeding by the time I see them in the room.
What Do I Tell My Patient? There is a medication called tranexamic acid that might help stop your nose bleed faster and get you out of the emergency department sooner. We also think that it makes the blood clot stronger, so there is less chance that you will start bleeding again later this week. It requires that I place this piece of cotton soaked in the medication in your nose for about ten minutes. We don’t know of any major side effects. Would you like to try it?
Keener Kontest: Last weeks’ winner was Simon McCormick an EM consultant from South Yorkshire. He knew Prontosil was the first sulfa drug and was discovered by German physician and chemist Gerhard Domagk in 1932.
Listen to the SGEM podcast on iTunes to hear this weeks’ question. If you know the answer send an email to TheSGEM@gmail.com with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.
#SGEMHOP
SGEMHOP: Now it is your turn SGEMers. What do you think of this episode? Tweet your comments using #SGEMHOP. What questions do you have? Ask them on the SGEM blog. The best social media feedback will be published in AEM.
Also, don’t forget those of you who are subscribers to Academic Emergency Medicine can head over to the AEM home page to get CME credit for this podcast and article. We will put the process on the SGEM blog:
- Go to the Wiley Health Learning website
- Register and create a log in
- Search for Academic Emergency Medicine – “March”
- Complete the five questions and submit your answers
- Please email Corey (coreyheitzmd@gmail.com) with any questions or difficulties.
Other FOAMed:
Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.
- Holbrook et al. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012.
- Zahed et al. A new and rapid method for epistaxis treatment using injectable form of tranexamic acidtopically: a randomized controlled trial. Am J EM 2013
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