Final Mini-CAT: Tranexamic acid for epistaxis

Brief description of patient problem/setting

A 68-year-old male with Hx of CAD s/p PCI (on clopidogrel and aspirin), presents to the ED for an episode of epistaxis with large amount of blood that did not resolve with external nasal compression. The resident on his case asks his attending if they should try topical tranexamic acid (TXA). The attending states she has never tried this before and is unsure if it is an effective treatment strategy.

Search Question: Is topical tranexamic acid (TXA) an effective alternative to standard treatment in managing epistaxis?

 

PICO search terms:

P	I	C	O
Epistaxis	Topical tranexamic acid	Placebo	Control of bleeding
Nasal hemorrhage	Topical TXA	Standard treatment	Cessation of bleeding
Nosebleed		Topical vasoconstrictor	Reduction in rebleeding
		Topical anesthetic
		Packing/pressure

 

Search tools and strategy used:

Filters/limits use for all 3 search tools: last 5 years, MEDLINE, English, free full article/text

 

PubMed: (terms = topical tranexamic acid AND epistaxis) + filters above  54 results

Cochrane: (terms = tranexamic acid AND epistaxis) +filters above  1 Cochrane review, 34 trials

JAMA: (terms = tranexamic acid AND epistaxis) + some filters above  5 results

GoogleScholar: (terms = topical tranexamic acid AND epistaxis) + filters above  794 results

 

How I narrowed my choices:

Limiting my choices to only articles from the past 5 years via filters on these databases really narrowed down what had resulted from my searches. Some studies that showed up only observed the effects of the oral or injected forms of TXA, which I excluded, since I wanted to focus on the topical version. Although I specifically searched for “epistaxis,” many results interestingly included studies that focused on other forms of bleeding, such as intracranial, hemoptysis, or vaginal bleeding. And while many article titles and abstracts did match my PICO terms and question, I did not have full access to all of them (especially on the Cochrane database), so I was limited to what I had full access to. Another way that I narrowed my choices was by focusing on articles that applied to a general population (or those on blood thinners, because this is a common presentation in the ED and it applied to my patient scenario); so I excluded some articles that focused on very specific populations, for example those with Von Willebrand factor deficiency. The only website I had difficulty narrowing my results to were with Google Scholar, which provided many relevant studies with my search. In this case I focused on articles that were recent and came from highly regarded sources.

 

 

Articles Chosen:

1. “Tranexamic acid for patients with nasal haemorrhage (epistaxis)”

Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517002/

 

Citation: Joseph, J., Martinez-Devesa, P., Bellorini, J., & Burton, M. J. (2018). Tranexamic acid for patients with nasal haemorrhage (epistaxis). The Cochrane database of systematic reviews, 12(12), CD004328. https://doi.org/10.1002/14651858.CD004328.pub3

 

Type of study: Systematic review

 

Abstract

Background: Epistaxis (nosebleed) most commonly affects children and the elderly. The majority of episodes are managed at home with simple measures. In more severe cases medical intervention is required to either cauterise the bleeding vessel, or to pack the nose with various materials. Tranexamic acid is used in a number of clinical settings to stop bleeding by preventing clot breakdown (fibrinolysis). It may have a role in the management of epistaxis as an adjunct to standard treatments, reducing the need for further intervention.

Objectives: To determine the effects of tranexamic acid (oral, intravenous or topical) compared with placebo, no additional intervention or any other haemostatic agent in the management of patients with epistaxis.

Search methods: The Cochrane ENT Information Specialist searched the Cochrane ENT Register (via CRS Web); Central Register of Controlled Trials (CENTRAL) (via CRS Web); PubMed; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 29 October 2018.

Selection criteria: Randomised controlled trials (RCTs) of tranexamic acid (in addition to usual care) compared with usual care plus placebo, usual care alone or usual care plus any other haemostatic agent, to control epistaxis in adults or children.

Data collection and analysis: We used the standard methodological procedures expected by Cochrane. The primary outcomes were control of epistaxis: re‐bleeding (as measured by the proportion of patients re‐bleeding within a period of up to 10 days) and significant adverse effects (seizures, thromboembolic events). Secondary outcomes were control of epistaxis as measured by the time to stop initial bleeding (the proportion of patients whose bleeding is controlled within a period of up to 30 minutes); severity of re‐bleeding (as measured by (a) the proportion of patients requiring any further intervention and (b) the proportion of patients requiring blood transfusion); length of hospital stay and other adverse effects. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.

Main results: We included six RCTs (692 participants). The overall risk of bias in the studies was low. Two studies assessed oral administration of tranexamic acid, given regularly over several days, and compared it to placebo. In the other four studies, a single application of topical tranexamic acid was compared with placebo (one study) and a combination of epinephrine and lidocaine or phenylephrine (three studies). All participants were adults.

Tranexamic acid versus placebo: For our primary outcome, control of epistaxis: re‐bleeding (proportion re‐bleeding within 10 days), we were able to pool data from three studies. The pooled result demonstrated a benefit of tranexamic acid compared to placebo, the risk of re‐bleeding reducing from 67% to 47% (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.56 to 0.90; three studies; 225 participants; moderate‐quality evidence).

When we compared the effects of oral and topical tranexamic acid separately the risk of re‐bleeding with oral tranexamic acid reduced from 69% to 49%, RR 0.73 (95% CI 0.55 to 0.96; two studies, 157 participants; moderate‐quality evidence) and with topical tranexamic acid it reduced from 66% to 43%, RR 0.66 (95% CI 0.41 to 1.05; single study, 68 participants). We rated the quality of evidence provided by the single study as low, therefore it is uncertain whether topical tranexamic acid is effective in stopping bleeding in the 10‐day period after a single application. No study specifically sought to identify and report our primary outcome: significant adverse effects (i.e. seizures, thromboembolic events).

The secondary outcome time to stop initial bleeding (proportion with bleeding controlled within 30 minutes) was measured in one study using topical tranexamic acid and there was no evidence of a difference at 30 minutes (RR 0.79, 95% CI 0.56 to 1.11; 68 participants; low‐quality evidence). No studies reported the proportion of patients requiring any further intervention (e.g. repacking, surgery, embolisation). One study of oral tranexamic acid reported the proportion of patients requiring blood transfusion and found no difference between groups: 5/45 (11%) versus 6/44 (14%) (RR 0.81, 95% CI 0.27 to 2.48; 89 participants; low‐quality evidence). Two studies reported hospital length of stay. One study reported a significantly shorter stay in the oral tranexamic acid group (mean difference (MD) ‐1.60 days, 95% CI ‐2.49 to ‐0.71; 68 participants). The other study found no evidence of a difference between the groups.

Tranexamic acid versus other haemostatic agents: When we pooled the data from three studies the proportion of patients whose bleeding stopped within 10 minutes was significantly higher in the topical tranexamic acid group compared to the group receiving another haemostatic agent (70% versus 30%: RR 2.35, 95% CI 1.90 to 2.92; 460 participants) (moderate‐quality evidence).

Adverse effects across all studies: Five studies recorded ‘adverse effects’ in a general way. None found any difference between the groups in the occurrence of minor adverse effects (e.g. mild nausea and diarrhoea, ‘bad taste’ of gel). In one study a patient developed a superficial thrombophlebitis of both legs following discharge, however it is not reported in which group this occurred. No “other serious adverse effect” was reported in any study.

Authors’ conclusions: We found moderate‐quality evidence that there is probably a reduction in the risk of re‐bleeding with the use of either oral or topical tranexamic acid in addition to usual care in adult patients with epistaxis, compared to placebo with usual care. However, the quality of evidence relating solely to topical tranexamic acid was low (one study only), so we are uncertain whether or not topical tranexamic acid is effective in stopping bleeding in the 10‐day period after a single application. We found moderate‐quality evidence that topical tranexamic acid is probably better than other topical agents in stopping bleeding in the first 10 minutes.

There have been only three RCTs on this subject since 1995. Since then there have been significant changes in nasal cauterisation and packing techniques (for example, techniques including nasal endoscopy and more invasive approaches such as endoscopic sphenopalatine artery ligation). New trials would inform us about the effectiveness of tranexamic acid in light of these developments.

 

 

 

2. “Efficacy of topical tranexamic acid in epistaxis: A systematic review and meta-analysis”

Link: https://www-sciencedirect-com.york.ezproxy.cuny.edu/science/article/pii/S0735675721008779

 

Citation: Janapala, R. N., Tran, Q. K., Patel, J., Mehta, E., & Pourmand, A. (2022). Efficacy of topical tranexamic acid in epistaxis: A systematic review and meta-analysis. The American Journal of Emergency Medicine, 51, 169–175. https://doi.org/10.1016/j.ajem.2021.10.043 

 

Type of study: Systematic review and meta-analysis

 

Abstract

Introduction

Epistaxis is a very common presentation in the emergency department (ED), accounting for approximately 1 in 200 ED visits in the United States. Currently, standard practice includes the initial use of topical anesthetics and vasoconstrictors, followed by more invasive treatments such as nasal packing, cauterization or surgical ligation for refractory cases. Over the years several studies have investigated the potential use of topical Tranexamic Acid (TXA) in the management of epistaxis. We have conducted a meta-analysis to assess the efficacy of topical TXA versus other standard practices or placebo in the management of epistaxis.

 

Methods

PubMed and Scopus databases were searched from inception to April 2021. We included randomized controlled trials and observational studies investigating the efficacy of TXA in bleeding cessation in epistaxis in adults. The primary outcome measured was the prevalence of bleeding cessation after treatment at first assessment. Other outcomes were bleeding reoccurrence between 24 and 72 h and at 7–8 days. A random-effects model was used to estimate odds ratio (OR) for outcomes.

 

Results

A total of eight studies were included in the analysis, including seven randomized trials and one retrospective study. We included a total of 1299 patients, 596 (46%) received TXA while 703 (54%) received control treatment (placebo, lidocaine plus vasoconstrictors or local anesthetics). Patients who were treated with TXA were 3.5 times (OR 3.5, 95% CI 1.3–9.7) more likely to achieve bleeding cessation at the first assessment. Patients treated with TXA had 63% (OR 0.37, 95% CI 0.20–0.66) less likelihood of returning due to rebleeding at 24–72 h.

 

Conclusion

Topical TXA is associated with better bleeding cessation rates after treatment compared to the standard practices. 

 

 

3. “Topical Tranexamic Acid versus Phenylephrine-lidocaine for the Treatment of Anterior Epistaxis in Patients Taking Aspirin or Clopidogrel; a Randomized Clinical Trial”

 

Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720853/pdf/aaem-9-e6.pdf

 

Citation: Amini, K., Arabzadeh, A., Jahed, S., & Amini, P. (2020). 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), e6. https://doi.org/10.22037/aaem.v9i1.875

 

Type of study: Randomized Clinical Trial

 

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 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%) 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.

 

 

4. “Topical Tranexamic Acid Compared With Anterior Nasal Packing for Treatment of Epistaxis in Patients Taking Antiplatelet Drugs: Randomized Controlled Trial”

Link: https://onlinelibrary.wiley.com/doi/epdf/10.1111/acem.13345

Citation: Zahed, R., Mousavi Jazayeri, M. H., Naderi, A., Naderpour, Z., & Saeedi, M. (2017). Topical tranexamic acid compared with anterior nasal packing for treatment of epistaxis in patients taking antiplatelet drugs: Randomized Controlled Trial. Academic Emergency Medicine, 25(3), 261–266. https://doi.org/10.1111/acem.13345

Type of study: Randomized Control Trial

 

Abstract:

Objective: We evaluated the efficacy of topical application of the injectable form of tranexamic acid (TXA)compared with anterior nasal packing (ANP) for the treatment of epistaxis in patients taking antiplatelet drugs (aspirin, clopidogrel, or both) who presented to the emergency department (ED).

Methods: A randomized, parallel-group clinical trial was conducted at two EDs. A total of 124 participants were randomized to receive topical TXA (500 mg in 5 mL) or ANP, 62 patients per group. The primary outcome was the proportion of patients in each group whose bleeding had stopped at 10 minutes. Secondary outcomes were the rebleeding rate at 24 hours and 1 week, ED length of stay (LOS), and patient satisfaction.

Results: Within 10 minutes of treatment, bleeding was stopped in 73% of the patients in the TXA group, compared with 29% in the ANP group (difference=44%, 95% confidence interval, 26% to 57%; p<0.001). Additionally, rebleeding was reported in 5 and 10% of patients during the first 24 hours in the TXA and the ANP groups, respectively. At 1 week, 5% of patients in the TXA group and 21% of patients in the ANP group had experienced recurrent bleeding (p=0.007). Patients in the TXA group reported higher satisfaction scores (median [interquartile range {IQR}], 9 [8–9.25]) compared with the ANP group (median [IQR]=4[3–5]; p<0.001). Discharge from the ED in<2 hours was achieved in 97% of patients in the TXA group versus 13% in the ANP group (p<0.001). There were no adverse events reported in either group.

Conclusions: In our study population, epistaxis treatment with topical application of TXA resulted in faster bleeding cessation, less rebleeding at 1 week, shorter ED LOS, and higher patient satisfaction compared with ANP.

 

 

5. “Evaluating Effectiveness of Nasal Compression With Tranexamic Acid Compared With Simple Nasal Compression and Merocel Packing: A Randomized Controlled Trial”

Link: https://www-sciencedirect-com.york.ezproxy.cuny.edu/science/article/pii/S0196064419302495

Citation: Sedat Akkan, Şeref K. Çorbacıoğlu, Halit Aytar, Emine Emektar, Seda Dağar, Yunsur Çevik,

Evaluating Effectiveness of Nasal Compression With Tranexamic Acid Compared With Simple Nasal Compression and Merocel Packing: A Randomized Controlled Trial, Annals of Emergency Medicine,

Volume 74, Issue 1,2019, Pages 72-78, ISSN 0196-0644, https://doi.org/10.1016/j.annemergmed.2019.03.030. (https://www.sciencedirect.com/science/article/pii/S0196064419302495)

 

Type of study: Randomized Control Trial

 

Abstract:

Study objective

The primary objective of this study is to compare the effectiveness of 3 treatment protocols to stop anterior epistaxis: classic compression, nasal packing, and local application of tranexamic acid. It also aims to determine the frequency of rebleeding after each of these protocols.

 

Methods

This single-center, prospective, randomized controlled study was conducted with patients who had spontaneous anterior epistaxis. The study compared the effect of 3 treatment options, tranexamic acid with compression but without nasal packing, nasal packing (Merocel), and simple nasal external compression, on the primary outcome of stopping anterior epistaxis bleeding within 15 minutes.

 

Results

Among the 135 patients enrolled, the median age was 60 years (interquartile range 25% to 75%: 48 to 72 years) and 70 patients (51.9%) were women. The success rate in the compression with tranexamic acid group was 91.1% (41 of 45 patients); in the nasal packing group, 93.3% (42 of 45 patients); and in the compression with saline solution group, 71.1% (32 of 45 patients). There was an overall statistically significant difference among the 3 treatment groups but no significant difference in pairwise comparison between the compression with tranexamic acid and nasal packing groups. In regard to no rebleeding within 24 hours, the study found rates of 86.7% in the tranexamic acid group, 74% in the nasal packing group, and 60% in the compression with saline solution group.

 

Conclusion

Applying external compression after administering tranexamic acid through the nostrils by atomizer stops bleeding as effectively as anterior nasal packing using Merocel. In addition, the tranexamic acid approach is superior to Merocel in terms of decreasing rebleeding rates.

 

 

Author (Date)	Level of Evidence	Sample/Setting (# of subjects/ studies, cohort definition etc. )	Outcome(s) studied	Key Findings	Limitations and Biases
Jonathan Joseph,  Pablo Martinez‐Devesa, Jenny Bellorini, Martin J Burton, and Cochrane ENT Group (2018)	Systematic review	-6 RCTs (4 used topical txa and 2 used oral) -692 participants -all participants were adults who had epistaxis requiring intervention – Patients were treated with tranexamic acid (in addition to usual care) compared to placebo, no treatment or any other agent used to stop bleeding	-Primary: Control of epistaxis, re-bleeding, significant adverse effects -Secondary: time to stop initial bleeding, severity of re-bleeding, length of hospital stay, other adverse events	-It is uncertain whether topical TXA is effective in stopping bleeding in the 10‐day period after a single application. -TXA was shown to be better at stopping patients bleeding within 10 minutes in comparison to other hemostatic agents (70% vs 30%). -The number of RCTs included were very limited.More updated information is needed.	-Quality of evidence relating solely to topical txa was low (one study only), so this article is uncertain whether or not topical txa is effective in stopping bleeding in the 10‐day period after a single application -3 of the 6 RCTs were conducted over 20 years ago -Quality of evidence for the outcomes assessed was moderate or low
Rajesh Naidu Janapala, Quincy K. Tran, Jigar Patel, Esha Mehtaa, Ali Pourmanda (2022)	Systematic review and meta-analysis	-7 RCTs, 1 retrospective study -1299 participants (596 received txa vs 703 in the control group)	-Primary outcomes: bleeding cessation after treatment with TXA at first re-assessment by the study authors. -Secondary outcomes: recurring bleeding between 24-72 h and 7–8 days	-Pts treated with topical TXA were 3.5x more likely to cessation of bleeding in comparison to any control treatment (nasal packing, topical vasoconstrictors, placebo). -TXA had higher rates of patient satisfaction compared to other existing treatment modalities. -The rate of rebleeding within 1-3 days was lower in the TXA group. -No statistically significant difference in the occurrence of adverse events between TXA and other groups.	-4 RCTs with concern for risk of bias -Majority of studies were not double-blinded -Small # of studies -Did not perform further statistical analyses for association of patients’ characteristic (like HTN, anticoagulant/antiplatelet use)
Keyvan Amini,  AmirAhmad Arabzadeh, Sevda Jahed, Payman Amini (2021)	Randomized Control Trial	-Prospective, double-blind, parallel-group, RCT -Pts in the ED w anterior epistaxis and who take aspirin or clopidogrel. -100 patients – Excluded: multiple trauma, hereditary hemorrhagic or plt disorders, hemophilia, renal dysfxn, or obvious bleeding from other areas	-Primary: bleeding cessation time -Secondary: bleeding recurrence, length of hospital stay, and the relationship btwn bleeding recurrence with sex, HTN, and DM	-Topical TXA was faster in time to stop bleeding in comparison to phenylephrine + lidocaine. -Bleeding recurrence and time to discharge, were also significantly lower in the TXA group compared to phenylephrine + lidocaine. -NNH of the TXA treated group was 7.1.	-Small sample size -Lack of an objective measurement index for the bleeding cessation
Zahed, R., Mousavi Jazayeri, M. H., Naderi, A., Naderpour, Z., & Saeedi, M. (2017).	Randomized Controlled Trial	-Randomized, parallel-group clinical trial conducted at 2 EDs. -124 participants (62 with topical TXA and 62 with anterior nasal packing) and all were taking antiplatelet drugs (aspirin, clopidogrel, or both) -Those included had persistent bleeding after 20 min of manual compression	-Primary: proportion of pts in each group whose bleeding stopped at 10 min. -Secondary: rebleeding rate at 24 hrs and 1 week, ED length of stay, and pt satisfaction	Topical TXA significantly better at stopping bleeding within 10 minutes, in comparison to ANP. Rebleeding within 24 hrs was higher in the ANP group (10%) compared to the TXA group (5%). Recurrent bleeding within 1 week was lower in the TXA group. TXA had higher satisfaction scores. TXA group had significantly shorter ED length of stay compared to ANP. No adverse events reported in either group.	-Those w/ posterior epistaxis were excluded -Physicians and pts were not blinded to treatment -Did not stratify tx assignment by the specific antiplatelet the pt was taking, so cannot make conclusions about the relative benefit of the study tx on the basis of either antiplatelet agent or a combination of the agents. -There was a higher proportion of pts with a Hx of epistaxis in the TXA group compared with the ANP group (so benefits of TXA may be underestimated).
Sedat Akkan, Şeref K. Çorbacıoğlu, Halit Aytar, Emine Emektar, Seda Dağar, Yunsur Çevik (2019)	Randomized Controlled Trial	-Single-center, prospective, RCT -135 pts who had spontaneous anterior epistaxis -All pts were 18 y/o or older -excluded: those on anticoagulant, hemodynamic instability, AMS, traumatic epistaxis, known bleeding disorder	-Primary: cessation of bleeding within 15 min -Secondary: rate of rebleeding within 24 hrs	-For stopping epistaxis within 15 min, success in the compression + txa = 91.1%; in nasal packing =  93.3%; in the compression + saline = 71.1% (no statistically significant difference btwn the txa and nasal packing groups) – 7 of 45 pts in the nasal packing group c/o severe pain and requested procedure termination -The Txa group had less rebleeding than the other two groups	-Study was done outside of the US (Turkey) -Neither the physician nor the pts were blind to the nasal packing in the nasal packing group because of the nature of tx -Small sample size -Nosebleeds were not classified based on severity -Only used a specific type of nasal packing (Merocel), others may be more effective or comfortable.

 

 

Brief Summary of Conclusions:

#1. Joseph et. al. (2018): Whether topical TXA is effective in stopping bleeding in the 10‐day period after a single application is uncertain. TXA was more effective at stopping bleeding within 10 minutes in comparison to other hemostatic agents (epi and lido or phenylephrine) (70% vs 30%).

 

#2. Janapala et. al. (2022): Patients treated with topical TXA were 3.5x more likely to have cessation of bleeding in comparison to any control treatment (nasal packing, topical vasoconstrictors, placebo). TXA had higher rates of patient satisfaction and lower rate of rebleeding. No statistically significant difference in the occurrence of adverse events between TXA and other groups.

 

#3. Amini et. al. (2021): Topical TXA was faster in cessation of bleeding in comparison to phenylephrine + lidocaine. Bleeding recurrence and time to discharge, were significantly lower in the TXA group compared to phenylephrine + lidocaine. For example, those whose hospital stay lasted <1 hour comprised of 19 pts in the TXA group and 3 in the phenylephrine + lidocaine group; for patients that needed to stay >4 hours at the hospital, there were 2 in the TXA group and 18 in the phenylephrine + lido group.

 

#4. Zahed et. al. (2017): Topical TXA was better at stopping bleeding within 10 minutes than anterior nasal packing (ANP). Rebleeding within 24 hrs was higher in the ANP group (10%) compared to the TXA group (5%). Recurrent bleeding within 1 week was lower in the TXA group. Those in the TXA group had a median patient satisfaction score of 9 versus ANP group with a score of 4 (p<0.001). Discharge from the ED in<2 hours was achieved in 97% of patients in the TXA group versus 13% in the ANP group (p<0.001). No adverse events reported in either group.

 

#5. Akkan et. al. (2019): No statistical difference in success between compression + TXA versus nasal packing for stopping epistaxis within 15 min. Seven out of 45 pts in the nasal packing group c/o severe pain. The TXA group had less rebleeding.

 

 

Overarching conclusions: Topical TXA is an effective method of epistaxis management and may be superior to other methods in terms of reduced rebleeding rates and shorter length of stay. The outcome of patient satisfaction was not primarily focused on in several studies, but still very important. Patients treated with topical TXA had better satisfaction/comfort than those treated with more invasive treatments like nasal packing (with similar efficacy in epistaxis management).

 

 

 

Clinical Bottom Line:

Weight of evidence (in order from highest to lowest) and explanations:

Janapala et. al. (2022, article #2): This is a systematic review and meta-analysis, which is the highest quality level of evidence for this type of research question. It reviewed a total of 7 RCTs and 1 retrospective study. It had the largest sample size of almost 1300 participants, and it was just published this year in The American Journal of Emergency Medicine. This study conducted thorough analyses of the biases involved in the studies analyzed. I appreciated that topical TXA was compared to a wide variation of control treatment, including placebo, epinephrine + lidocaine or oxymetazoline, or phenylephrine +lidocaine. This gives us a better look at whether topical TXA should be considered an alternative for epistaxis management in the ED or if the standard treatments should just be continued.

Joseph et. al. (2018, article #1): This is a systematic review, which is of higher quality level of evidence than the rest of the articles which were RCTs. This article also comes from a highly regarded source, Cochrane. I ranked this study lower than the first because the data included was scarce and limited. It also had a smaller sample size (>600 participants), although this is larger than sample sizes of the rest of the RCTs below. This was also ranked lower than the first systematic review because the authors assessed the outcomes to be of moderate-low quality.

Amini et. al. (2021, article #3): Unlike the other two RCTs, below, this was the only one that was double-blinded. Although this one had the smallest sample size (100 subjects), this number was not very far off from the other RCTs’ sample sizes. This study was also only published last year and had few limitations. I also ranked this higher than the other two RCTs because this study compared topical TXA to another topical treatment instead of nasal packing like the other 2 below, and nasal packing is usually used as a last option after conservative tx with pressure and topical medication has failed.

Akkan et. al. (2019, article #5): This RCT compared TXA + compression vs anterior nasal packing. Out of the RCTs included here, this study had the largest sample size. While a limitation mentioned was that neither the physicians nor the patients were blinded, I would not consider this a major factor in the weight of evidence because it would be difficult to blind the subjects due to the nature of nasal packing itself. I ranked this one lower than the Amini study because this study done by Akkan et. al. only used Merocel nasal packing, which has been largely replaced by RhinoRocket in the US; therefore, the data gathered here may not be applicable to the local patient population.

Zahed et. al. (2017, article #4): This article was ranked last because it was the oldest published and had many limitations. First, it compared topical TXA versus nasal packing in patients taking antiplatelets. Although this data is important to know for this particular population, which is why I included this study in the first place, it also only applies to patients taking antiplatelets, so the data cannot be applied to the rest of the population. There were also other significant limitations as mentioned in the Summary of Evidence table above.

 

 

My articles included 2 systematic reviews and 3 RCTs, all published within the last 5 years. All of the articles had strong data suggesting that topical TXA was effective in cessation of acute epistaxis and may be better than several modalities of management standardly being used (anterior nasal packing, vasoconstrictors + analgesics, etc). While one of the systematic reviews (Cochrane) had inconclusive and low-quality results regarding rebleeding, stating a reduction in rebleeding was not significantly seen in those treated with TXA; I would argue, however, that they had a very limited amount of data. The other 4 articles included here supported topical TXA’s ability in reducing the occurrence of rebleeding, especially in comparison to other standard treatments (noting comparable or even better cessation of bleeding with txa). Topical TXA was also shown to be effective in managing epistaxis in those taking antiplatelets like aspirin and/or clopidogrel. The clinical bottom line derived from the data collected here is that topical TXA is an effective alternative treatment for managing epistaxis in the ED, even in those on aspirin and/or clopidogrel. Not only were the outcomes from my PICO search terms addressed (control of bleeding, rebleeding occurrence), but TXA was also shown in some of these studies to improve patient satisfaction and shorten length of ED stay.