YAJEM-57390; No of Pages 4

American Journal of Emergency Medicine xxx (2018) xxx–xxx

Contents lists available at ScienceDirect

American Journal of Emergency Medicine

journal homepage: www.elsevier.com/locate/ajem

Topical tranexamic acid for the treatment of acute epistaxis in the

emergency department☆
Asha R. Birmingham, PharmD a, Nathan D. Mah, PharmD a,⁎, Ran Ran, MD b, Matthew Hansen, MD b
a
Department of Pharmacy, Oregon Health & Science University, United States
b
Department of Emergency Medicine, Oregon Health & Science University, United States

a r t i c l e i n f o a b s t r a c t

Article history: Objective: To evaluate the effectiveness and potential benefits of topical tranexamic acid (TXA) in the manage-
Received 6 September 2017 ment of acute epistaxis.
Received in revised form 8 March 2018 Methods: Retrospective review was performed among all patients presenting to the institution's emergency de-
Accepted 19 March 2018 partment (ED) with epistaxis between September 2014 and August 2016. Patients achieving hemostasis with
Available online xxxx
standard of care agents, such as oxymetazoline, lidocaine, or epinephrine were excluded. The primary outcome
was the ED length of stay (LOS). Secondary outcomes included the incidence of hospital admission, otolaryngol-
Keywords:
Tranexamic acid
ogist consultation, nasal packing, prophylactic antibiotic use, and ED visit for rebleeding within seven days of
Acute epistaxis treatment.
Emergency medicine Results: Among 122 patients, 30 received topical TXA (500 mg injectable solution soaked onto packing material
Pharmacy and applied to the affected nostril) and 92 were managed with standard care. Nearly half (46.7%) of TXA-treated
Nosebleed subjects received TXA either alone or in combination with standard of care agents as their initial treatment strat-
Intranasal egy. No significant difference was observed in the ED LOS (272 vs 232 min in TXA and standard care arms, respec-
Topical tively, p = 0.26). However, TXA was associated with a significant reduction in otolaryngologist consults (30.0% vs
Otolaryngology
65.2%, p = 0.002) and nasal packing (16.7% vs 23.9%, p = 0.003).
Conclusions: This investigation did not demonstrate a significant difference in ED LOS among patients with acute
epistaxis treated with topical TXA or standard care. However, this data does add to existing evidence that TXA
may be associated with a reduction in resource utilization, suggesting it may provide more effective bleeding
control. Overall, more data is needed to confirm the potential benefits of this practice.
© 2018 Elsevier Inc. All rights reserved.

1. Introduction oxymetazoline, epinephrine, and lidocaine, in combination with nostril

It is estimated that 60% of the world's population will experience ep-
istaxis throughout their lifetime [1]. Most nosebleeds are self-limiting
and can be managed in an outpatient setting, but approximately 6% of
cases require medical attention, making epistaxis a common chief com-
plaint in the emergency department (ED).
Initial management of epistaxis includes application of topical vaso-
constrictors and local anesthetics, such as phenylephrine,
☆ The authors of this manuscript have nothing to disclose concerning possible financial
or personal relationships with commercial entities that may have a direct or indirect
interest in the subject matter of this document. This research did not receive any specific
grant from funding agencies in the public, commercial, or not-for-profit sectors. All
authors had full freedom to explore the data and analyze results independently. All
authors are aware of content presented here and had authority in the final decision to
submit material for publication. This study was approved by the institutional review
board (OHSU eIRB ID: 00016425; approved September 19, 2016).
⁎ Corresponding author at: CR9-4 3181 SW Sam Jackson Park Rd. Portland, OR 97239,
United States.
E-mail address: mahn@ohsu.edu (N.D. Mah).
compression [2]. Refractory bleeds require alternative methods, such as
nasal packing, cauterization, or surgical ligation which may require in-
volvement of an otolaryngologist. Nasal packing and balloon systems
are often kept in place for 1 to 5 days, can cause patient discomfort,
and may require prophylactic antibiotics and a follow-up visit for re-
moval. The need for removal can be avoided with some absorbable
products, such as oxidized cellulose or topical thrombin. However,
these methods can be costly compared to some first line medications
[1,3]. Complications of nasal packing can include increased bleeding
from traumatic packing, infection, tissue necrosis, or toxic shock syn-
drome with prolonged packing [2]. Thus, avoidance of these methods
using adjunct therapies is preferable.
The use of some topical hemostatic agents, including tranexamic
acid (TXA), chitosan, and aminocaproic acid have been reported in the
literature for the management of epistaxis [4-7]. TXA, in particular, has
been used topically in gel and injectable forms for epistaxis treatment,
as well as orally and as intranasal administration for the prevention of
rebleeding [4-7]. In one randomized, single-center, parallel group
study among 216 patients with idiopathic anterior epistaxis, topically

https://doi.org/10.1016/j.ajem.2018.03.039
0735-6757/© 2018 Elsevier Inc. All rights reserved.

Please cite this article as: Birmingham AR, et al, Topical tranexamic acid for the treatment of acute epistaxis in the emergency department, Amer-
ican Journal of Emergency Medicine (2018), https://doi.org/10.1016/j.ajem.2018.03.039
2 A.R. Birmingham et al. / American Journal of Emergency Medicine xxx (2018) xxx–xxx
applied injectable TXA was associated with a higher portion of patients
achieving cessation of bleeding within 10 min compared to topical epi-
nephrine and lidocaine followed by anterior nasal packing [4]. Second-
ary outcomes also demonstrated significantly fewer rebleeding events
within 24 h or seven days and shorter ED length of stay (LOS) after
treatment with TXA. Topical TXA's comparatively low cost, ease of ad-
ministration, and avoidance of follow-up visits compared to conven-
tional nasal packing techniques make it an attractive option for
treatment of epistaxis in the ED. It also has the potential to decrease re-
source utilization by minimizing the need for specialist consultation and
reducing ED LOS. The objective of this retrospective cohort study was to
assess the effectiveness and potential benefits of the addition of topical
TXA to the standard of care compared to standard care alone for the
treatment of epistaxis in the ED.
2. Methods
2.1. Setting
This single center, retrospective chart review was conducted at
Oregon Health & Science University (OHSU), a 573-bed academic
medical center and Level 1 trauma center in Portland, Oregon. It was
approved by the institutional review board and informed consent was
waived.
2.2. Selection of subjects
Subjects were identified for eligibility if they had visited the ED be-
tween September 2014 and August 2016 with a primary diagnosis of
epistaxis, as identified by ICD9/10 codes. Included patients must have
received the entirety of their epistaxis care at the same institution;
those receiving initial treatment at outside facilities before transfer to
OHSU were excluded. Those with significant traumatic etiologies who
were sent directly to the OR and those with minor bleeds not requiring
any interventions were excluded. All patients were treated according to
provider discretion. In order to ensure a comparable severity of epistaxis
between the comparator groups, patients achieving hemostasis solely
with traditional first line therapies including oxymetazoline, lidocaine,
or epinephrine were also excluded from the study. Patients with any al-
lergies to the study medications were excluded.
2.3. Data collection
Retrospective chart review of each epistaxis-related hospital en-
counter was performed. Subjects treated at any point during their stay
with topically-applied TXA solution for injection were categorized into
the treatment arm. All other subjects with sustained bleeding after the
previously-mentioned first line therapies were categorized into the
control arm. The primary outcome was the ED LOS among subjects
not admitted to the hospital. This was originally designed to be mea-
sured from the time of first epistaxis treatment to discharge; however,
due to a lack of accurate records for time of administration, the primary
outcome was later revised to total ED LOS. Secondary outcomes in-
cluded the incidence of hospital admission, otolaryngologist consulta-
tion, nasal packing, prophylactic antibiotic use, and ED visit for
rebleeding within seven days of treatment.
2.4. Statistical analysis
The primary outcome was assessed by use of the Mann-Whitney U
test. Categorical data were compared with Chi-Square or Fisher Exact
tests, as appropriate, using a significance level of 0.05.
Please cite this article as: Birmingham AR, et al, Topical tranexamic acid for the treatment of acute epistaxis in the emergency department, Amer-
ican Journal of Emergency Medicine (2018), https://doi.org/10.1016/j.ajem.2018.03.039
3. Results
3.1. Population
Among patients receiving treatment for epistaxis in the ED during
the study period, 41 achieved hemostasis with first line agents alone
and were excluded. Another five were excluded for receipt of initial
treatment at an outside facility and 4 eloped before any treatment was
administered. A remaining 122 patients met inclusion criteria; 30 re-
ceived TXA and 92 were treated with standard care alone. Among 74 pa-
tients with the location of epistaxis recorded, 78.3% were anterior
bleeds. Notably, patients in the TXA group showed higher rates of anti-
platelet therapy, anticoagulant therapy, and disorders associated with
risk of bleeding compared to the standard care group, though only the
use of left ventricular assist devices (LVADs) was statically significant
(Table 1).
3.2. Interventions and outcomes
The majority of subjects in either study arm received initial therapy
with a traditional first line agent, though this was less common in the
TXA arm (Table 2). Nearly half (46.7%) of patients in the TXA arm re-
ceived TXA as their initial treatment, either alone or concomitantly
with traditional standard of care agents. Among those receiving TXA,
administration consisted of 500 mg injectable TXA solution per nostril,
soaked onto cotton pledgets or nasal tampons (n = 29) or 100 mg aero-
solized (n = 1).
The number of patients admitted to the hospital did not differ be-
tween TXA and standard care arms (Table 3). After removing those ad-
mitted to the hospital, the primary outcome was available in 24 TXA and
68 standard care subjects, and was not significantly different between
groups (median ED LOS 272 vs 232 min, respectively, p = 0.26).
During the entirety of their ED or hospital stay, fewer patients
treated with TXA received chemical cauterization (13.3% vs 28.3%, p =
0.099) or surgical intervention (3.3% vs 7.6%, p = 0.450) compared to
those in the standard care arm, though these were not statistically sig-
nificant. There was a significant reduction observed in the number of
otolaryngologist consultations and use of nasal packing among patients
treated with TXA (Table 3). Four and 13 patients received transfusions
in the TXA and standard care arms, respectively, and no thrombotic
events were recorded up to 10 days after treatment.
4. Discussion
Identification of new treatment strategies for epistaxis could have
numerous advantages with regards to cost, resource utilization, patient
discomfort, and risk for complications. An alternative treatment strat-
egy, such as the addition of topical TXA to standard care, could provide
a significant improvement in the current management of epistaxis.
One randomized, single-center, parallel group trial has compared
the effect of topical TXA to usual anterior nasal packing [4]. Study sub-
jects (n = 216) presenting to the ED with anterior nosebleeds received
either a 15 cm cotton pledget soaked in 500 mg of injectable TXA, or a
pledget soaked in epinephrine (1:100000) and lidocaine 2% for 10 min
followed by anterior packing with tetracycline-soaked pledgets. In this
study, cessation of bleeding was achieved within 10 min in more pa-
tients treated with TXA than nasal packing (71% vs 31.2%, odds ratio
[OR] 2.28, 95% confidence interval [CI] 1.68–3.09, p b 0.001) and TXA-
treated subjects were more likely to have short ED lengths of stay (dis-
charge in ≤2 h 95.3% vs 6.4%, OR 14.8, 95% CI 7.2–30.4, p b 0.001). Addi-
tionally, TXA was associated with a reduction in rebleeding events
within 24 h (4.7% vs 12.8%, OR 0.36, 95% CI 0.14–0.98, p = 0.034) and
seven days (2.8% vs 11%, OR 0.26, 95% CI 0.07–0.88, p = 0.018). No com-
plications or adverse events were observed, and patients in the TXA
group reported higher satisfaction rates than the anterior packing
group. However, the control group in this study was treated with
 A.R. Birmingham et al. / American Journal of Emergency Medicine xxx (2018) xxx–xxx 3

Table 1
Baseline Characteristics.

Patient characteristic, n (%) TXA (n = 30) Standard Care (n = 92) p-value

Median age, years (Interquartile ratio) 63 (36 to 71) 62 (32 to 69) 0.96
Male 21 (70.0) 40 (43.5) 0.01
Antiplatelet therapy (aspirin, clopidogrel, prasugrel, or ticagrelor) 10 (33.3) 28 (30.4) 0.77
Anticoagulant therapy (warfarin, apixaban, rivaroxaban, dabigatran, edoxaban, enoxaparin, fondaparinux, or heparin) 9 (30.0) 17 (18.5) 0.18
History of hypertension (listed on patient's problem list or taking antihypertensive medication) 9 (30.0) 30 (33.0) 0.76
Hereditary hemorrhagic telanagiectasia 6 (20.0) 13 (14.1) 0.44
Hemophilia or von Willebrand factor deficiency 3 (10.0) 6 (6.5) 0.53
Thrombocytopenia or Paris trousseau syndrome 5 (16.7) 6 (6.5) 0.09
Left ventricular assist device 6 (20.0) 0 (0) b0.001
Trauma or surgery 4 (13.3) 24 (26.1) 0.15

anterior nasal packing which is not standard of care for all patients with
anterior epistaxis. In many environments, packing is reserved for pa-
tients who fail other therapies due to its inherent discomfort and the
risk of re-bleeding when the packing is removed. In addition, TXA was
used as first line treatment in this study whereas the present study uti-
lizes it as an additional or alternative therapy, which the authors believe
to be a more pragmatic approach.
Topical TXA has also been studied using gel formulation. A random-
ized, placebo-controlled trial among 68 patients with ongoing nose-
bleeds was performed using 15 mL of topically applied 10% TXA gel
[5]. No significant differences were observed. A higher portion of pla-
cebo-treated subjects had cessation of bleeding within 30 min (60% vs
76%, p = 0.16), though the TXA group had significantly more moderate
and severe bleeds at baseline [8]. The TXA group also had a nonsignifi-
cant (NS) reduction in rebleeding within eight days (11% vs 31%, p =
NS) and 10 days (44% vs 66%, p = NS). Of note, TXA is not commercially
available in a gel formulation at this time, and the topical administration
of intravenous TXA described in the present study may be more feasible
in practice.
In the current study, there was no significant difference observed in
total ED LOS and, in fact, a numerically longer LOS was seen in TXA-
treated patients. Though many of the baseline differences between the
study arms did not meet statistical significance (Table 1), they could
help to explain this observation. For instance, patients on antiplatelet
or anticoagulation therapy and those with underlying bleeding disor-
ders, like thrombocytopenia or LVADs, may have been perceived as
higher risk and treated more aggressively with TXA and a longer obser-
vation period. Topical TXA was associated with several benefits, includ-
ing reduction in otolaryngologist consultations (OR 0.23, 95% CI 0.09–
0.56); post-hoc analysis also shows decreased composite use of nasal
packing, cauterization, and surgical intervention (combined OR 0.59,
Table 2
Interventions.
Interventions TXA Standard care
(n = 30) (n = 92)
95% CI 0.01–0.20), suggesting that the practice may be associated with
an overall reduction in resource utilization and cost.
There are several notable limitations to this study, including some
that could help explain the discrepancies seen between the current
and prior studies in regards to the primary outcome. Minor bleeds
treated with only first line agents were excluded from this investigation
in an attempt to select a population with a more homogenous severity
of epistaxis. However, it was not possible to ensure similarity between
groups in this respect due to the study's retrospective design. A numer-
ically higher but not statistically significant prevalence of
anticoagulation and underlying disorders predisposing patients to
bleeding (Table 1) in the TXA arm could suggest that patients with
higher bleed risk were preferentially treated with TXA. This could con-
tribute to the increased LOS observed among these patients. TXA was
added as an optional therapy at our institution and used at the discre-
tion of the ED provider. As such, this study has an inevitable potential
for selection bias and intergroup heterogeneity which may be reflected
in the baseline characteristics and treatments used.
Using a retrospective design, investigators could not reliably account
for all the confounding variables that could have affected LOS. The pri-
mary outcome was originally designed to account for some variability
in the time it takes for initial evaluation of a patient in the ED. However,
due to missing data regarding timing of medication administration, the
primary outcome had to be revised. Notably, the ED LOS in this study
was also longer than that seen in the previous study by Zahed et al.
(for comparison, only 4.3% of patients treated with standard care and
no patients treated with TXA were discharged within two hours), sug-
gesting that differences in standard practice or patient populations
could have existed between these two single-center investigations [4].
In summary, the treatment of refractory epistaxis with standard of
care and usual second line techniques presents several potential con-
cerns, including increased cost, patient discomfort, prolonged ED visits,
risk of complications, and the need for follow-up visits. Evidence
supporting use of topical TXA for acute epistaxis is promising, but lim-
ited. The data presented here suggest that topical TXA used as an ad-
junct to standard of care may be associated with statistically
significant decrease in the consultation of otolaryngologist and nasal
p-value

Initial treatment, n (%) Table 3

First line agents 16 (53.3) 73 (79.3) 0.005 Outcomes.
TXA ± first line agents 14 (46.7) n/a b0.001
Nasal packing 0 13 (14.1) 0.037 Primary outcome⁎ TXA (n = 24) Standard care (n = 68) p-value
Silver nitrate cauterization 0 6 (6.5) 0.334 Median ED LOS, min 272 232 0.26
Secondary outcome, n (%) TXA (n = 30) Standard care (n = 92) p-value
Treatments during admission to the Emergency Department, n (%) Hospital admission 6 (20.0) 24 (26.1) 0.33
First line agents 23 (76.7) 81 (88.0) 0.127 Otolaryngologist consult 9 (30.0) 60 (65.2) 0.002
Nasal packing 14 (46.7) 70 (76.1) 0.003 Nasal packing 14 (46.7) 70 (76.1) 0.003
Silver nitrate or electrical cauterization 4 (13.3) 25 (27.2) 0.145 Prophylactic antibiotic use 4 (13.3) 16 (17.4) 0.78
Surgical intervention 1 (3.3) 7 (7.6) 0.678 Return visit for rebleeding 7 (23.3) 18 (19.6) 0.85
within 7 days
First line agents = oxymetazoline, lidocaine, epinephrine; Nasal packing = Surgicel,
Floseal, Merocel, or Rhinorockets; Surgical intervention = surgical ligation, transarterial li- ED = emergency department; LOS = length of stay.
gation, surgical cauterization. ⁎ Excluding patients admitted to the hospital.

Please cite this article as: Birmingham AR, et al, Topical tranexamic acid for the treatment of acute epistaxis in the emergency department, Amer-
ican Journal of Emergency Medicine (2018), https://doi.org/10.1016/j.ajem.2018.03.039
4 A.R. Birmingham et al. / American Journal of Emergency Medicine xxx (2018) xxx–xxx

packing. This adds to existing evidence suggesting an overall reduction References

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Source(s) of support in the form of equipment, drugs, or grants (in-
cluding grant numbers)
None.
The name of organization and date of assembly if the article has
been presented
Oregon Society of Health-Systems Pharmacists Annual Seminar,
April 29th, 2017.
Northwestern States Regional Pharmacy Residency Conference, May
13th, 2017.
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Please cite this article as: Birmingham AR, et al, Topical tranexamic acid for the treatment of acute epistaxis in the emergency department, Amer-
ican Journal of Emergency Medicine (2018), https://doi.org/10.1016/j.ajem.2018.03.039