Source: Joseph J, Martinez-Devesa P, Bellorini J, Burton MJ. Tranexamic acid for patients with nasal haemorrhage (epistaxis). Cochrane Database Syst Rev 2018;12:CD004328.
Study Popoulation: Six trials comprising 692 adult patients with epistaxis
Efficacy Endpoints: Rebleeding within 10 days
Harm Endpoints: Serious adverse events such as seizure and thromboembolic events; minor adverse events such as nausea, vomiting, or intolerance
Narrative: Epistaxis is a common reason for patients to present to the emergency department (ED), reflecting one of every 200 ED visits in the United States.1 While many cases of epistaxis are self-limiting, those requiring medical treatment can be associated with significant time and health care costs.2 Additionally, nasal packing and hemostatic matrices can be painful and require the patient to return for at least one follow-up visit. Therefore, identifying an effective and inexpensive treatment is of particular importance. Tranexamic acid is an antifibrinolytic agent that has been proposed as one potential modality for this.
The Cochrane Review discussed here included randomized controlled trials comparing tranexamic acid (TXA) in any formulation (e.g., delivered orally, intravenously, or topically) with usual care versus usual care with placebo, usual care with any other hemostatic agent, or usual care alone.3 The primary outcome was the proportion of patients with rebleeding within 10 days and significant adverse events (i.e., seizures, thromboembolic events). Among the six trials (n = 692 patients), two studies used oral TXA,4, 5 while the remaining four used topical TXA.6, 7, 8, 9 For the primary outcome (n = 225 patients), TXA was associated with lower rates of rebleeding at 10 days (47% vs. 67%; relative risk [RR] = 0.71, 95% confidence interval = 0.56 to 0.90; absolute risk difference = 20%; number needed to treat = 5; moderate-quality evidence) compared to placebo. There were no significant differences between groups for adverse events, although only five of the trials reported adverse events.4, 5, 7, 8, 9 The included trials did not report outcomes requiring further intervention (e.g. repacking, surgery, embolization).
Another recent systematic review of topical TXA in epistaxis identified faster discharge rates, reduced rebleeding at 24 hours, and greater patient satisfaction with TXA, but no difference in rebleeding at 30 minutes.10 While the studies utilized different search strategies, both were informed by similar studies in their reviews. The current review further supports the potential value of this intervention.10
Caveats: Interpreting the results of the systematic review and meta-analysis discussed here warrants some caution. First, there was significant clinical heterogeneity in the study populations, with differences in the routes of administration (i.e., oral vs. topical), comparator groups (placebo vs. anterior nasal packing), and primary outcomes. Additionally, only three studies assessed the primary outcome of rebleeding at 10 days, while several other trials had different individual study outcomes (e.g., bleeding control within 30 minutes). Moreover, there was poor reporting of adverse events in the included studies. However, no significant adverse events were reported and most events were considered minor in nature (e.g., nausea, vomiting). Further, while rebleeding at 10 days is a clinically significant outcome, there were limited data on other ED-relevant outcomes (e.g., time to bleeding cessation, time to discharge, return to ED rates). Anterior epistaxis might also respond differently to treatment than posterior epistaxis. Only three of the included trials assessed the location of bleeding and only enrolled patients with anterior epistaxis. Other trials did not specify the location of bleeding. Another important limitation is that a large number of patients in some of the trials were on antiplatelet agents (i.e., aspirin, clopidogrel, or both); this could have affected the outcomes and contributed to the clinical heterogeneity in response to treatment. Future studies should identify what subgroup of patients (e.g., anterior vs. posterior epistaxis, antiplatelets use) are most likely to benefit from TXA, which delivery route is most effective, and how to better assess differences in adverse events.
The existing evidence supports the efficacy of TXA to reduce the risk of rebleeding at 10 days among adult patients. Despite inconsistent reporting of adverse events, the occurrence of such events appears to be unlikely, particularly with topical use. Therefore, we have assigned a color recommendation of green (benefit > harm) to the use of TXA for epistaxis.
The original manuscript was published in Academic Emergency Medicine as part of the partnership between TheNNT.com and AEM.
Author: Michael Gottlieb, MD; Alex Koyfman, MD; Brit Long, MD
Published/Updated: May 3, 2019
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