TXA for Epistaxis Associated with Antiplatelet Agents

Published

Zahed R. "Topical Tranexamic Acid Compared With Anterior Nasal Packing for Treatment of Epistaxis in Patients Taking Antiplatelet Drugs: Randomized Controlled Trial". Academic Emergency Medicine. 2018. 25(3):261-266.
PubMed • Full text • PDF

Clinical Question

In adult patients treated in the emergency department for epistaxis associated with antiplatelet drug use, was local application of tranexamic acid (TXA) superior to antibiotic-coated packing?

Bottom Line

Among patients with epistaxis associated with antiplatelet drug use, topical tranexamic acid (TXA) was superior to standard antibiotic-coated nasal packing in terms of arrest of bleeding, rebleeding risk, emergency department length of stay, and patient satisfaction.

Major Points

Non-traumatic intractable epistaxis is a common diagnosis in the emergency department, and standard therapy with nasal packing can be uncomfortable for patients and yield suboptimal results. Tranexamic acid (TXA) is a relatively inexpensive antifibrinolytic agent which has been used topically to control bleeding in a number of settings.

The present study by Zahed and colleagues evaluated over 200 adults presenting to the emergency department with intractable epistaxis associated with recent administration of antiplatelet agents. Patients were randomized to either TXA, in which cotton was soaked with TXA 500 mg prior to administration, or to standard packing with epinephrine and lidocaine. Packing was removed after 3 days. Bleeding arrest at 10 minutes was improved in the TXA group (73% versus 29%), as was discharge within 2 hours (97% versus 13%), rebleeding at 1 week (5% versus 21%), and patient satisfaction.

This is one of several studies evaluated as part of a meta analysis which found favorable outcomes with TXA in epistaxis. Notably, these results differ from those of NoPAC, which found no significant improvement in outcomes among patients receiving TXA compared to standard packing. This difference may have arisen because NoPAC studied a sicker patient population and included patients receiving anticoagulant (more than half had received anticoagulant therapy compared to none in the present study).

There are several limitations with this trial, similar to a prior study (TXA for Epistaxis) by the same authors. The first was the untrue blinding of the participants and the clinicians. There was also an imbalance between the two groups with more history of epistaxis in the TXA group. There are several other commercially available treatments for epistaxis as well as other formulations of TXA. Nevertheless, given the wide availability of TXA and the ease of use in this study, TXA-soaked packing may be a promising treatment for anterior epistaxis.

Guidelines

American Academy of Otolaryngology (2020)

The use of oral or topical TXA for nosebleed was the subject of a recent Cochrane review.106 While benefits were noted with reduction of rebleed with use of TXA, this review stated that only 3 of the 6 included studies were performed after 1995, with all 3 conducted in Iran (including the 2 studies by Zahed et al). Given these studies of moderate quality and newer techniques of epistaxis treatment with endoscopes and cautery, additional study of TXA is needed to understand indications and efficacy for nosebleed control.

Design

• Two-center, parallel-group, randomized clinical trial
• N=216 adults presenting to the ED with epistaxis associated with recent antiplatelet drug use
  • Tranexamic acid (n=62)
  • Anterior packing (n=62)
• Setting: 2 academic emergency departments in Iran
• Enrollment: 2015-2016
• Mean follow-up: 7 days
• Analysis: Intention to treat
• Primary Outcome: Bleeding arrest by 10 minutes

Population

Inclusion Criteria

• Acute, new or recurrent, ongoing anterior epistaxis
• Receipt of antiplatelet drugs (aspirin, clopidogrel, or both)
• Bleeding requiring further treatment following compression for 20 minutes

Exclusion Criteria

• Traumatic epistaxis
• Current anticoagulant drug use
• Inherited bleeding disorders (including hemophilia)
• Inherited platelet disorders
• International normalize ratio > 1.5
• Shock
• Visible bleeding vessel
• History of renal disease

Baseline Characteristics

From the TXA group.

• Demographics: Mean age 58 years, 60% male
• Labs: Platelet 298, INR 1.05, PTT 32 seconds
• History of epistaxis: 53%
• History of aspirin: 81%

Interventions

• Patients were randomly assigned to TXA or standard anterior packing groups.
  • TXA group: TXA 500 mg/5 mL soaked cotton packing was used, removed after bleeding arrest.
  • Anterior packing group: Packing was soaked in epinephrine (1:100000) + lidocaine (2%) for 10 minutes, then packing covered with tetracycline and removed after 3 days.

Outcomes

Comparisons are anterior packing vs. TXA.

Primary Outcomes

Bleeding stop time ≤10 min, %

29 vs. 73 (ARR 44, 95% CI 26 to 57, P<0.001)

Secondary Outcomes

Median bleeding stop time, min [IRQ]

15 [10-20] vs. 10 [10-15] (P < 0.001)

Discharge time ≤2 h, %

13 vs. 97 (ARR 84, 95% CI 71 to 91, P<0.001)

Rebleeding in the first 24 h, %

10 vs. 5 (ARR -5, 95% CI -15 to 5, P=0.299)

Rebleeding from procedure until 1 week, %

21 vs. 5 (ARR -16, 95% CI -28 to -4, P=0.007)

Patient satisfaction rate (visual analogue scale), median [IRQ]

4 [3-5] vs. 9 [8-9] (P<0.001)

Adverse Events

Complications in the ED (nausea, vomiting, intolerance), %

5 vs. 10 (ARR 5, 95% CI -5 to 15, P = 0.299)

Serious adverse events

None reported in either arm

Criticisms

• Did not include posterior epistaxis
• Did not stratify by antiplatelet agent use, so can only comment on class in general
• Full blinding was not conducted due to product and protocol differences; only analysts were blinded
• Excluded major risk factors for bleeding in this study, limiting external validity
• Severity of epistaxis not classified
• Higher rate of history of epistaxis in the TXA group
• Complication of "intolerance" not well defined

Funding

• Not stated