# Nebulized Tranexamic Acid in Low- to Medium-abundance Hemoptysis: A Retrospective Study of Current Practices

Virgile Caban, Julie Tronchetti, Jean-Baptiste Lovato, Stéphanie Martinez, Hervé Dutau, Philippe Astoul

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Virgile Caban, Julie Tronchetti, Jean-Baptiste Lovato, Stéphanie Martinez, Hervé Dutau, et al. Nebulized Tranexamic Acid in Low- to Medium-abundance Hemoptysis: A Retrospective Study of Current Practices. 2025, pp.791 - 793. 10.1016/j.arbres.2025.06.014. hal-05525471

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Scientific Letter

Nebulized Tranexamic Acid in Low- to
Medium-abundance Hemoptysis: A
Retrospective Study of Current Practices

To the Director,

<figure><img src="image_4.png" /></figure>

Hemoptysis is a common symptom in pulmonology, account-
ing for up to 10% of consultations and 15% of admissions in some
series [1]. It refers to bleeding from the subglottic airways and
varies in severity from mild hemoptico sputum seen in up to
90% of cases – to massive hemoptysis, which carries a mortal-
ity risk exceeding 50% [2,3]. Regardless of severity, it constitutes
a medical emergency requiring hospitalization and potentially
specialized care. Bronchial arterial embolization (BAE) remains
the standard treatment, with bleeding control rates between 70%
and 99% [3]. However, this technique depends on immediate
access to interventional radiology, which is unavailable in many
hospitals. Consequently, frontline clinicians – such as pulmo-
nologists, intensivists, and emergency physicians – have sought
accessible alternatives to manage hemoptysis or bridge patients
until embolization is feasible. Tranexamic acid (TXA), a synthetic
antifibrinolytic derived from Epsilon-Amino-Caproic Acid, inhibits
plasminogen activation and delays fibrinolysis [4]. Known for its
efficacy in trauma-related bleeding, it is widely used via intra-
venous routes in emergency settings. More recently, TXA has been
administered via inhalation to treat hemoptysis, aiming to deliver
local hemostasis with fewer systemic side effects. While promising,
this off-label practice is supported mainly by case series and limited
trials. Hankerson et al. [5] first reported inhaled TXA use in 2015 for
palliative management of low-volume hemoptysis. In 2018, Wand
et al. [6] conducted a double-blind RCT demonstrating cessation of
hemoptysis within five days in 96% of patients treated, compared to
50% in the placebo group. Gopinath et al. [7] later compared inhaled
and intravenous TXA, reporting reduced bleeding, fewer emboliza-
tions, and shorter hospital stays in the inhaled group. Additional
case series have echoed these findings, but the evidence remains
sparse and heterogeneous [8–15]. Given the limited but encour-
aging data, we conducted a retrospective, bi-centric study with a
larger sample to assess the effectiveness of nebulized TXA (NebTXA)
in patients hospitalized for mild to moderate hemoptysis. Our pri-
mary aim was to characterize patients responding to NebTXA, and
secondarily, to compare them with those who ultimately required
embolization.

We conducted a retrospective, observational, bi-centered study
at the Aix-Pertuis Intercommunal Hospital Center and the Mar-
seille North University Hospital (France) between 2020 and 2023.
Ethical approval was granted via the Health Data Access Por-
tal (PADS: GK25MX); patient data were anonymized. Included

were adult patients hospitalized for mild to moderate hemopy-
sis (<200 mL/24 h or <100 mL in a single episode), excluding those
with severe or unstable conditions, TXA use before admission, or
contraindications. Hemoptysis severity and exclusion criteria were
defined by clinical and hemodynamic thresholds, including oxygen
or vasopressor need, respiratory rate ≥30, or mechanical venti-
lation. Patients were identified through ICD-10 code R04.2 and
had received nebulized tranexamic acid (NebTXA) 500 mg TID via
nebulization over ≥15 min. Collected data included demograph-
ics, underlying diseases (airway, vascular, malignant, iatrogenic),
clinical and imaging findings, hemoptysis characteristics, and out-
comes.

The primary objective was to determine the clinical profile of
patients in whom NebTXA successfully controlled bleeding with-
out requiring invasive management (interventional bronchoscopy,
embolization, or surgery). Secondary objectives included evaluat-
ing time to hemoptysis resolution, hospital length of stay, need
for embolization after treatment failure, and overall, in-hospital
mortality. We also compared clinical characteristics between
responders and non-responders (embolized patients precisely)
to identify predictors of treatment failure. Data was analyzed
using RStudio (2022.07.2). Categorical variables were compared
using χ² or Fisher's exact test, continuous variables by t-test or
Mann-Whitney U. Logistic regression (univariate and multivari-
ate) identified predictors of NebTXA failure, with significance set
at *p* < 0.05.

Between January 2020 and December 2023, 189 patients met inclusion criteria (62 at Aix-Pertuis, 127 at Marseille North). Most were male (69.8%), median age 63 years (IQR 52–73), and heavy smokers (52.9%). Comorbidities included cardiovascular diseases (43.4%), COPD/emphysema (15.3%), and bronchiectasis (4.2%). At admission, 25.4% were on antiplatelet therapy and 26.5% on curative anticoagulation. Hemoptysis was recent (<7 days in 77.3%), recurrent (77.8%), low volume (<100 mL in 69.8%), and required oxygen in 25.4% of cases. A thoracic angio-CT was performed in 88.9%, revealing consolidations or ground-glass opacities in 47.6% and an embolizable vascular target in 40.8% (92.2% bronchial origin). Main etiologies were bronchopulmonary cancers (39.2%, with 52.7% inaugural), infections (27.5%), and iatrogenic causes (12.7%). Median hospital stay was 7 days (IQR 5–12). Nineteen patients died (10.1%), mostly from cancer progression or hospital-acquired infections; none were attributed to NebTXA. NebTXA achieved hemoptysis cessation within 5 days in 162 patients (85.7%), including 55 with cancer. Treatment failure (27 patients) was more frequent in those with cancer (70.4%), recurrent hemoptysis, and oxygen need. These patients also had longer stays (median 12 vs. 7 days). Bronchoscopy, embolization, and surgery were performed in 45.5%, 23.8%, and 1.1% of patients, respectively.
<table><caption>**Table 1**
Variables for patients undergoing embolization (multivariate analysis).</caption><thead><tr><th>Variable<sup>a</sup></th><th>Result (No. (%))</th><th>p-Value</th></tr></thead><tbody><tr><td><strong>Etiology</strong></td><td></td><td></td></tr><tr><td>Lung malignancy</td><td>28 (62.2)</td><td>0.0003</td></tr><tr><td>Infection</td><td>9 (20.0)</td><td>0.98</td></tr><tr><td>Acute exacerbation of COPD</td><td>0 (0.0)</td><td>0.20</td></tr><tr><td>Inflammation/immune disease</td><td>0 (0.0)</td><td>0.33</td></tr><tr><td>Vascular hypertrophy</td><td>7 (15.6)</td><td>0.26</td></tr><tr><td>Foreign body inhalation</td><td>0 (0.0)</td><td>1.00</td></tr><tr><td>Cardiac disease</td><td>0 (0.0)</td><td>1.00</td></tr><tr><td>Traumatic cause</td><td>0 (0.0)</td><td>1.00</td></tr><tr><td>Iatrogenic</td><td>0 (0.0)</td><td>0.004</td></tr><tr><td><strong>Anticoagulants/antiplatelets</strong></td><td></td><td></td></tr><tr><td>Antiplatelets</td><td>11 (24.4)</td><td>0.63</td></tr><tr><td>Anticoagulants (effective)</td><td>14 (31.1)</td><td>0.41</td></tr><tr><td><strong>Hemoptysis episode</strong></td><td></td><td>0.10</td></tr><tr><td>Single episode</td><td>6 (13.3)</td><td></td></tr><tr><td>Multiple episodes</td><td>39 (86.7)</td><td></td></tr><tr><td><strong>Hemoptysis abundance</strong></td><td></td><td>0.03</td></tr><tr><td>Little</td><td>23 (51.1)</td><td></td></tr><tr><td>Medium</td><td>22 (48.9)</td><td></td></tr><tr><td><strong>Hemoptysis past history</strong></td><td>11 (24.4)</td><td>0.24</td></tr><tr><td><strong>Oxygen requirement</strong></td><td>10 (22.2)</td><td>0.09</td></tr></tbody></table>

Embolization targeted bronchial arteries in 93.3% and was more common in moderate hemoptysis (48.9%, p = 0.03). As you can see in Table 1, a predominance of bronchopulmonary cancers (62.2%, p = 0.0003) was observed in embolized patients. Conversely, iatrogenic hemoptysis has never been embolized (0%, p = 0.004). An embolization procedure was performed more often and significantly in patients with moderately abundant hemoptysis (48.9% of patients) (p = 0.03). Mortality was lower (6.7%) although the difference with the non-embolized population was not significant (p = 0.571). Multivariate analysis (Table 2) confirmed bronchial cancer and moderate hemoptysis as predictors of NebTXA failure. Vascular anomalies and idiopathic causes were also associated with treatment failure. Antithrombotic therapy did not affect outcomes or mortality, which was higher in cancer patients with moder-

ate hemoptysis (57.9%, p = 0.0094) and oxygen dependence (57.9%, p = 0.0009).

Our cohort of 189 patients, mostly male smokers with cardiovascular comorbidities, reflects real-life presentations of hemoptysis. Nebulized tranexamic acid (NebTXA) appeared effective for mild to moderate bleeding, particularly in single-episode cases without oxygen dependence. Though not all findings reached significance, favorable trends were observed in infections, inflammatory diseases, and iatrogenic causes. This aligns with prior studies. Zhang et al. [16] confirmed the safety and local efficacy of inhaled TXA, while Alkazemi et al. [15] and Mahalingam et al. [17] supported its role in reducing procedures and hospital stay in non-massive hemoptysis. Our protocol (500 mg/5 mL, 3-4 times/day) matches these standards, reinforcing external validity. Antiplatelet and anticoagulant use did not affect outcomes, though in temporary discontinuation caution remains warranted. Shorter hospital stays suggest early symptom control with NebTXA, reflecting it may reduce the need for invasive procedures. Multivariate analysis identified bronchopulmonary cancer and moderate-volume bleeding as independent predictors of treatment failure and need for bronchial artery embolization (BAE). Patients undergoing bronchial artery embolization had more frequent, moderate-volume hemoptysis, fewer radiologic ground-glass opacities, and lower mortality. Most deaths were due to malignancy progression or complications, not NebTXA itself, reinforcing its safety. Compared to Wand et al. [6], our cohort included fewer patients with bronchiectasis, likely due to local referral patterns. NebTXA appeared beneficial in reversible etiologies, but spontaneous resolution may account for part of its effect. Our findings help identify most likely ideal candidates and high-risk profiles. Strengths include largest to date sample size and multivariate adjustments. Limitations involve retrospective design, limited power preventing initial primary objective, potential confounding, and local recruitment bias. Prospective studies are warranted to define NebTXA's place, especially in oncology and resource-limited settings.

This study describes a diverse real-life cohort of 189 patients and suggests that NebTXA may be relevant for managing low-to moderate-abundance hemoptysis, particularly in first episodes without oxygen therapy and involving reversible etiologies. However, this remains an exploratory analysis of a poorly standardized practice. In cases such as bronchopulmonary neoplasia, its use

<table><caption>**Table 2**
Variables analyzed in case of NebTXA failure (univariate and multivariate analysis) (CI: 95%).</caption><thead><tr><th>Variable</th><th>Univariate<br>(OR, 95% CI)</th><th>p-Value<br>(Univariate)</th><th>Multivariate<br>(OR, 95% CI)</th><th>p-Value<br>(Multivariate)</th></tr></thead><tbody><tr><td><strong>Etiology</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>Lung malignancy</td><td>3.5 (1.8-7)</td><td>0.0003</td><td>5.5 (1.4-31)</td><td>0.01</td></tr><tr><td>Infection</td><td>1 (0.4-2.3)</td><td>0.96</td><td>2.7 (0.7-15.2)</td><td>0.17</td></tr><tr><td>Acute exacerbation of COPD</td><td>0.2 (0-1.5)</td><td>0.12</td><td>0.5 (0-7.7)</td><td>0.66</td></tr><tr><td>Inflammation/immune disease</td><td>0.2 (0-2.1)</td><td>0.22</td><td>0.7 (0-10.6)</td><td>0.79</td></tr><tr><td>Vascular hypertrophy</td><td>1.9 (0.7-4.9)</td><td>0.20</td><td>5.8 (1.2-37)</td><td>0.02</td></tr><tr><td>Foreign body inhalation</td><td>0.6 (0-7.9)</td><td>0.75</td><td>2.5 (0-42)</td><td>0.68</td></tr><tr><td>Cardiac disease</td><td>0.6 (0-7.9)</td><td>0.75</td><td>1.4 (0-30)</td><td>0.85</td></tr><tr><td>Traumatic cause</td><td>1.1 (0-20)</td><td>1.97</td><td>2.5 (0-75)</td><td>0.63</td></tr><tr><td>Iatrogenic</td><td>0.1 (0-0.4)</td><td>0.001</td><td>0.4 (0-5.1)</td><td>0.52</td></tr><tr><td><strong>Anticoagulants/antiplatelets</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>Antiplatelets</td><td>1.1 (0.5-2.4)</td><td>0.80</td><td>1.1 (0.4-2.4)</td><td>0.90</td></tr><tr><td>Anticoagulants (effective)</td><td>1.4 (0.7-2.8)</td><td>0.40</td><td>1.5 (0.7-3.5)</td><td>0.32</td></tr><tr><td><strong>Hemoptysis episode</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>Single episode</td><td></td><td></td><td></td><td></td></tr><tr><td>Multiple episodes</td><td>2 (0.9-5.5)</td><td>0.10</td><td>1 (0.4-2.9)</td><td>0.99</td></tr><tr><td><strong>Hemoptysis abundance</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>Mild</td><td></td><td></td><td></td><td></td></tr><tr><td>Medium</td><td>2.1 (1.1-4.1)</td><td>0.03</td><td>2.2 (1-4.6)</td><td>0.04</td></tr><tr><td><strong>Hemoptysis past history</strong></td><td>1.6 (0.7-3.6)</td><td>0.23</td><td>1.1 (0.5-2.6)</td><td>0.83</td></tr><tr><td><strong>Oxygen requirement</strong></td><td>0.8 (0.4-1.7)</td><td>0.61</td><td>0.6 (0.2-1.4)</td><td>0.20</td></tr></tbody></table>

<footnote><sup>a</sup> Values expressed as number (percentage) unless otherwise indicated.</footnote>
should not replace consultation with interventional radiologists. These findings support future prospective studies comparing NebTXA to standard care, especially in centers lacking interventional capabilities.

### CRediT authorship contribution statement

- Virgile Caban: Conceptualization, data collection, analysis, manuscript drafting.

- Julie Tronchetti: Methodology, data interpretation, data review, manuscript review.

- Jean-Baptiste Lovato: Methodology, data collection, data interpretation.

- Stéphanie Martinez: Methodology, data collection, data review.

- Hervé Dutau: Supervision, critical revision of the manuscript.

- Philippe Astoul: Supervision, methodology, project administration, manuscript review.

### Declaration of generative AI and AI-assisted technologies in the writing process

Artificial intelligence tools were used to assist in editing and formatting but not in data analysis or content generation.

### Funding

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

### Conflicts of interest

The authors declare no conflicts of interest.

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Virgile Caban<sup>a, *,</sup>, Julie Tronchetti<sup>a</sup>, Jean-Baptiste Lovato<sup>a, b</sup>, Stéphanie Martinez<sup>c</sup>, Hervé Dutau<sup>a, d</sup>, Philippe Astoul<sup>a, b, d</sup>

Corresponding author.

E-mail address: Virgile.CABAN@ap-hm.fr (V. Caban).

<footnote><sup>a</sup> Department of Thoracic Oncology, Pleural Diseases, and Interventional Pulmonology, Hôpital Nord, Marseille, France</footnote>

<footnote><sup>b</sup> Aix-Marseille University, Marseille, France</footnote>

<footnote><sup>c</sup> Respiratory Diseases Department, Aix-Pertuis Intercommunal Hospital Center, Aix-en-Provence, France</footnote>

<footnote><sup>d</sup> Aix-Marseille University, AP-HM, INSERM, INRAE, C2VN, Marseille, France</footnote>