Effectiveness and safety of antifibrinolytic agents in the management of pulmonary haemorrhage: A systematic review with narrative synthesis

Abstract

BACKGROUND

Pulmonary haemorrhage is an uncommon but potentially fatal presentation, most often recognised clinically as haemoptysis. Management is centred on airway protection, physiological stabilisation, identification of the bleeding source, and treatment of the underlying cause. Tranexamic acid (TXA) has been increasingly used as an adjunctive haemostatic therapy, particularly by nebulised or inhaled routes, but its role remains poorly defined.

AIM

To review the available evidence on the effectiveness and safety of antifibrinolytic therapy, particularly TXA, in patients with pulmonary bleeding presenting as haemoptysis.

METHODS

A systematic review with narrative synthesis was performed in accordance with the PRISMA 2020 statement. PubMed, EMBASE, Scopus, the Cochrane Library, and Web of Science were searched from inception to September 28, 2025. Randomised trials, observational studies, cohort studies, and case series evaluating oral, intravenous, topical/endobronchial, inhaled, or nebulised antifibrinolytic therapy were considered. Outcomes included bleeding cessation, recurrence, mortality, need for bronchoscopy or bronchial artery embolisation, length of stay, and adverse events. Due to marked clinical and methodological heterogeneity, meta-analysis was not performed, and findings were synthesised narratively.

RESULTS

Ten studies were included: Three randomised trials, retrospective cohorts, and small case series. In stable adults with non-massive haemoptysis, nebulised TXA was associated with faster bleeding control, shorter admission, and fewer invasive interventions. Systemic TXA showed a possible mortality and length-of-stay benefit in a large administrative cohort, but this evidence remains observational. In contrast, an intensive care unit (ICU)-based retrospective study found higher adjusted mortality among patients receiving nebulised TXA, probably reflecting confounding by indication, as TXA was more likely to be used in sicker patients. Paediatric critical care and extracorporeal membrane oxygenation cohorts reported high rates of bleeding cessation with inhaled or endotracheal TXA and few adverse events. Reported complications were uncommon, mainly transient bronchospasm and rare thrombotic events in patients with pre-existing risk factors. Certainty of evidence was highest, though still limited, for nebulised TXA in stable non-massive adult haemoptysis, and very low for evidence in ICU, paediatric, and extracorporeal membrane oxygenation populations.

CONCLUSION

TXA appears to be a useful adjunct for short-term haemostatic control in selected patients with haemoptysis, particularly when delivered locally by nebulised, inhaled, or topical routes. The strongest signal of benefit is in stable, non-massive haemoptysis; evidence in severe or ICU-level bleeding remains uncertain. Hence most included studies were not designed to reliably detect thromboembolism, bronchospasm, airway clot burden, or delayed complications, safety conclusions should be regarded as provisional. TXA should not delay airway control, bronchoscopy, embolisation, or treatment of the underlying cause. Better prospective studies with standardised severity definitions, route-specific dosing, and clinically meaningful outcomes are needed.

Key Words: Pulmonary hemorrhage; Hemoptysis; Tranexamic acid; Antifibrinolytic agents; Administration; Inhalation

Core Tip: This systematic review with narrative synthesis shows that the apparent effect of tranexamic acid (TXA) on haemoptysis outcomes depends heavily on clinical context: Nebulised TXA improves bleeding control in stable, non-massive haemoptysis, whereas higher mortality reported with TXA in intensive care cohorts most likely reflects confounding by indication rather than drug harm. Route, severity, and population must therefore be considered together when interpreting TXA evidence, rather than treating haemoptysis as a single condition or TXA exposure as uniform across settings.

INTRODUCTION

Pulmonary haemorrhage is a potentially fatal syndrome caused by bleeding into the pulmonary parenchyma or airways. In this review, the term is used broadly to encompass bleeding of pulmonary origin from any source. Haemoptysis refers specifically to expectoration of blood or blood-stained sputum, most commonly arising from the bronchial circulation. Diffuse alveolar haemorrhage is a distinct clinicopathological pattern in which bleeding originates from the pulmonary microvasculature and fills the alveolar spaces, usually in the context of capillaritis, vasculitis, immune-mediated disease, or coagulopathy; importantly, overt haemoptysis may be absent. Pulmonary bleeding may therefore present with haemoptysis, but can also manifest as otherwise unexplained anaemia, hypoxaemia, respiratory distress, diffuse pulmonary infiltrates, or rapid clinical deterioration when blood is not externally visible[1]. Its causes are broad and include bronchiectasis, infection, vasculitis, malignancy, trauma, coagulopathy, and iatrogenic complications after medical or surgical procedures[2]. Although many episodes of haemoptysis are mild and self-limiting, a smaller group of patients develop recurrent or clinically significant bleeding, repeated admissions, respiratory failure, and death. This burden is concentrated among patients with structural lung disease, cystic fibrosis, malignancy, poor cardiopulmonary reserve, and those requiring intensive care.

The clinical behaviour of haemoptysis depends less on the absolute volume of blood and more on the patient’s ability to maintain airway patency and gas exchange. In most cases, bleeding arises from the bronchial arterial circulation, a systemic high-pressure vascular bed that becomes fragile in the setting of chronic inflammation, infection, neovascularisation, and malignancy. This explains why bronchial artery embolisation remains a key definitive intervention in life-threatening haemoptysis. Pulmonary arterial bleeding is less common, but may occur with pulmonary embolism, vasculitis, pulmonary artery pseudoaneurysm, or direct vascular injury. Severe haemoptysis threatens life mainly through airway flooding, obstruction by blood or clot, atelectasis, ventilation-perfusion mismatch, and hypoxaemia, rather than exsanguination alone. This is especially relevant in patients with poor respiratory reserve, in whom even moderate bleeding may cause rapid decompensation.

Definitions of haemoptysis severity remain inconsistent. Traditional terms such as “massive” and “non-massive” haemoptysis are commonly used, but volume-based thresholds vary widely and are unreliable in practice because blood may be swallowed, mixed with secretions, or poorly quantified. A more useful clinical definition is functional: Haemoptysis becomes life-threatening when it causes respiratory compromise, haemodynamic instability, significant anaemia, need for transfusion, urgent bronchoscopy, embolisation, surgery, or ventilatory support. This lack of standardised severity classification is not a minor academic problem. It directly limits comparison between studies, weakens interpretation of treatment effects, and makes it difficult to define which patients are most likely to benefit from haemostatic therapies.

Management is therefore necessarily multimodal. Initial care focuses on airway protection, oxygenation, ventilation, haemodynamicstabilisation, and correction of reversible contributors such as anticoagulation or coagulopathy. Definitive management depends on severity and cause, ranging from conservative treatment and antimicrobials to bronchoscopy, bronchial artery embolisation, or surgery[3-7]. Bedside imaging, including point-of-care ultrasound, can support early assessment in acute dyspnoea[8]. Even with advances in bronchoscopy, interventional radiology, and critical care, recurrent or persistent haemoptysis remains difficult to manage, particularly when bleeding occurs in frail patients or in those with severe underlying pulmonary disease.

Antifibrinolytic therapy has therefore attracted interest as a practical adjunct for early bleeding control. Tranexamic acid (TXA) is a synthetic lysine analogue that inhibits plasminogen binding to fibrin, reduces plasmin-mediated clot degradation, and stabilises clot formation[5]. Its benefit in traumatic and perioperative haemorrhage is well established, including in large trauma and surgical bleeding datasets[6,7]. This has encouraged off-label use in pulmonary bleeding, where early clot stabilisation within the airway may reduce ongoing blood loss, improve airway clearance, and buy time while definitive diagnostic and source-directed interventions are arranged. Local administration through inhaled, nebulised, endobronchial, or topical routes is especially attractive because it may deliver high drug concentrations at the bleeding site while reducing systemic exposure.

However, the evidence base remains limited and clinically uneven. The optimal route, dose, timing, duration, and patient population for TXA in haemoptysis are still uncertain. Although TXA is generally regarded as safe, concerns remain about thromboembolic events and bronchospasm, particularly in patients with malignancy, cardiovascular disease, previous thrombosis, reactive airway disease, or concurrent anticoagulation[9-11]. Published studies are also heterogeneous, with variation in design, severity definitions, clinical setting, route of administration, and outcome reporting. Some studies suggest benefit in stable non-massive haemoptysis, particularly with inhaled or nebulised therapy, while others raise concern about interpretation in critically ill cohorts, where TXA may simply mark more severe bleeding and higher baseline mortality[12,13].

Given the clinical importance of haemoptysis, the increasing use of TXA, and the absence of standardised guidance, a careful synthesis of the available evidence is needed. This systematic review with narrative synthesis aims to appraise the effectiveness and safety of antifibrinolytic therapy (TXA and epsilon-aminocaproic acid), particularly TXA, in pulmonary bleeding presenting as haemoptysis across different ages, clinical settings, and routes of administration. The review also aims to clarify where TXA may fit within contemporary haemoptysis pathways, distinguishing its potential role as an adjunct for early haemostatic control from definitive interventions such as airway protection, bronchoscopy, embolisation, and treatment of the underlying cause.

MATERIALS AND METHODS

Study design and registration

This study was conducted as a systematic review with narrative synthesis, reported in accordance with the PRISMA 2020 statement[14]. The protocol was registered prospectively in PROSPERO (CRD420251151995) before completion of the final synthesis. Such protocol specified a possibility of meta-analysis; the decision to use narrative synthesis instead was made after study selection and data extraction, for the reasons given below, which represents the only deviation from the registered protocol.

The review was initially designed with the possibility of meta-analysis. However, after study selection and data extraction, quantitative pooling was not considered appropriate. The included studies differed substantially in design, population, bleeding severity, intervention route, dose, comparator, and outcome definition. Some studies evaluated stable adults with non-massive haemoptysis in emergency or ward settings, whereas others included critically ill adults, paediatric intensive care patients, or children supported with extracorporeal membrane oxygenation. Outcomes were also reported in incompatible ways, including time to bleeding cessation, cessation by different time points, bleeding volume, recurrence, need for bronchial artery embolisation, length of stay, and mortality. Pooling these data would have produced a statistically simple but clinically misleading estimate. For this reason, the findings were synthesised narratively.

Literature search strategy

A comprehensive literature search was undertaken across five electronic databases: PubMed, EMBASE, Scopus, the Cochrane Library, and Web of Science. All five databases were searched from inception to September 28, 2025, on the same date. The search strategy was developed to maximise sensitivity while maintaining clinical relevance. It included controlled vocabulary terms, including Medical Subject Headings where applicable, and free-text keywords. Boolean operators and truncation were used to capture variation in terminology. The PubMed strategy is shown below; full database-specific strategies for EMBASE, Scopus, the Cochrane Library, and Web of Science, adapted to each database’s syntax and controlled vocabulary, are provided in Supplementary material: (("Pulmonary Haemorrhage"[tiab] OR "Hemoptysis"[Mesh] OR hemoptysis[tiab] OR "lung bleeding"[tiab] OR "alveolar hemorrhage"[tiab]) AND ("Antifibrinolytic Agents"[Mesh] OR "Tranexamic Acid"[Mesh] OR tranexamic[tiab] OR TXA[tiab] OR "Aminocaproic Acid"[Mesh] OR aminocaproic[tiab] OR EACA[tiab] OR "aprotinin"[tiab])).

Searches were limited to studies published in English, with no restriction by publication date. The English-language restriction was applied for feasibility of full-text review and data extraction. Citation searching of the reference lists of included studies and relevant reviews was performed manually; clinical trial registries and grey literature sources were not searched. Reference lists of relevant primary studies and review articles were also screened manually to identify additional eligible studies not captured in the database search.

Eligibility criteria

Eligibility criteria were defined a priori using a Population, Intervention Comparison, Outcomes framework. The population of interest included paediatric, adult, and older patients with pulmonary haemorrhage or haemoptysis. The intervention of interest was antifibrinolytic therapy, including TXA or epsilon-aminocaproic acid, administered by oral, intravenous, inhaled, nebulised, topical, or endobronchial routes; non-TXA antifibrinolytics, such as epsilon-aminocaproic acid, were eligible for inclusion, but in practice TXA accounted for the great majority of identified and included evidence, and only one included study (the cystic fibrosis pathway study) used epsilon-aminocaproic acid in some episodes alongside TXA. Comparators included placebo, standard care, no antifibrinolytic therapy, or alternative haemostatic and supportive strategies, including bronchoscopy, bronchial artery embolisation, mechanical ventilation, or surgery, when reported. The primary outcomes were bleeding cessation and mortality. Secondary outcomes included recurrence of haemoptysis, need for invasive procedures, hospital or intensive care length of stay, mechanical ventilation, and adverse events, particularly thromboembolism and bronchospasm.

Randomised controlled trials, observational studies, retrospective cohorts, prospective cohorts, and case series were eligible. Studies were excluded if antifibrinolytic agents were used only for non-pulmonary bleeding, if pulmonary haemorrhage outcomes could not be extracted separately, or if the publication did not contain original clinical data. Narrative reviews, editorials, letters without primary data, and opinion articles were excluded from the evidence synthesis, although their reference lists were screened when relevant.

Study selection

All records identified through the database searches were imported into a reference management system (Covidence), and duplicates were removed. Titles and abstracts were screened against the predefined eligibility criteria. Full texts were then reviewed for studies that appeared eligible or where eligibility was uncertain from the abstract alone. Title/abstract screening and full-text assessment were performed by a single reviewer with an independent review by a second reviewer; disagreements were resolved by discussion between both authors. Study authors were not contacted for missing or unclear data.

Data extraction

Data were extracted using a standardised data collection form. Extracted variables included first author, year of publication, country, study design, sample size, patient demographics, clinical setting, haemoptysisaetiology, severity of bleeding, antifibrinolytic agent, route of administration, dose, frequency, duration, comparator, and reported outcomes. Data extraction was performed by a single reviewer with an independent review by a second reviewer; disagreements were resolved by discussion between both authors and reference back to the original article.

The main outcomes extracted were cessation of bleeding and mortality. Additional outcomes included recurrence of bleeding, requirement for bronchoscopy or bronchial artery embolisation, need for mechanical ventilation, hospital or intensive care length of stay, and reported adverse events, including thromboembolic complications and bronchospasm.

Risk of bias assessment

Methodological quality and risk of bias were assessed according to study design. Randomised controlled trials were evaluated using the Cochrane Risk of Bias tool, version 2 (RoB 2), while observational, retrospective, and case-series studies were assessed using the Newcastle-Ottawa Scale. Risk of bias assessments were summarised visually using the robvis tool, and a study-level risk-of-bias table with a brief justification for each domain-level judgement is provided in Table 1. Particular attention was given to confounding by indication, selection bias, inconsistent severity definitions, incomplete outcome reporting, and lack of standardised follow-up. Risk-of-bias assessment was performed by a single reviewer and checked by a second reviewer; disagreements were resolved by discussion. The certainty of evidence for the main outcomes was additionally summarized using a simplified Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)-informed approach, considering risk of bias, inconsistency, indirectness, imprecision, and publication bias (Table 2).

Table 1 Study-level risk-of-bias assessment with domain-level justification.

Study	Tool	Overall judgement	Justification
Wand et al[15]	RoB 2	Low risk	Double-blind, placebo-controlled, adequate randomisation and allocation concealment reported; outcome assessment blinded; low attrition; pre-specified outcomes reported
Gopinath et al[4]	RoB 2	Some concerns	Open-label design means lack of blinding of participants/clinicians could influence co-interventions and subjective outcomes (e.g., decision to embolise); randomisation and outcome data otherwise adequate
Bellam et al[22]	RoB 2	Some concerns	Single-blind pilot design with small sample size; underpowered for the pre-specified intervention-rate outcome, raising risk of bias from imprecision and possible selective emphasis on significant secondary endpoints
Al-Samkari et al[16]	NOS	Moderate risk	Before-after pathway design without concurrent control; patients act as their own historical comparator, so secular trends and regression to the mean cannot be excluded; outcome ascertainment was consistent within the pathway
Kinoshita et al[17]	NOS	Moderate risk	Large propensity-matched administrative cohort with robust ascertainment of mortality and length of stay; however, administrative coding cannot capture bleeding severity, indication for treatment, or unmeasured confounders, so residual confounding by indication remains likely
Bethuel et al[5]	NOS	Serious/critical risk	Retrospective multicentre cohort with strong likely confounding by indication (nebulised tranexamic acid preferentially used in more severely bleeding or deteriorating patients); treatment selection not randomised or adjusted for all relevant severity markers; mortality finding should not be read as a causal estimate
Alkazemi et al[21]	NOS	Moderate/serious risk	Retrospective matched cohort with a small treated group (n = 14), limiting power to detect true differences; matching reduces but does not eliminate confounding by indication
Alabdrabalnabi et al[20]	NOS	Serious/critical risk	Uncontrolled case series of three patients with no comparator; high risk of selective reporting and very limited generalisability
O'Neil et al[18]	NOS	Serious risk	Single-centre retrospective observational study without a comparator group; small sample (n = 19); outcome ascertainment based on clinical record review with no blinding
Singleton et al[19]	NOS	Serious risk	Retrospective ECMO-specific cohort without a comparator group; highly selected, anticoagulated population with multiple competing risks for bleeding outcomes

NOS: Newcastle-Ottawa Scale; RoB 2: Cochrane Risk of Bias tool, version 2; ECMO: Extracorporeal membrane oxygenation.

Table 2 Simplified GRADE-informed certainty of evidence for main outcomes.

Outcome	Population/setting	Certainty	Main reasons for rating
Bleeding cessation	Stable non-massive adult haemoptysis, nebulised TXA	Low	Two consistent randomised trials; downgraded for imprecision (small samples)
Mortality	ICU/mixed-acuity adult haemoptysis	Very low	Directly conflicting observational signals; serious risk of bias from confounding by indication; downgraded for inconsistency and risk of bias
Recurrence	Stable non-massive adult and CF haemoptysis	Low	Sparse data from one trial and one uncontrolled pathway study; downgraded for imprecision and indirectness
Need for invasive procedures	Stable non-massive adult haemoptysis, nebulised TXA	Low	Consistent direction across two randomised trials and observational data; downgraded for imprecision
Length of stay	Stable non-massive adult haemoptysis, nebulised TXA	Low	Consistent direction across trial and observational data; downgraded for imprecision and indirectness across settings
Adverse events (thromboembolism, bronchospasm)	All settings	Very low	Most studies not designed or powered to detect these events; inconsistent or absent reporting; serious risk of bias and imprecision
Bleeding cessation, safety, and feasibility	ICU, paediatric, and ECMO populations	Very low	Small, retrospective, uncontrolled studies with serious risk of bias and indirectness; downgraded on all major domains

Certainty ratings are based on a simplified application of GRADE domains (risk of bias, inconsistency, indirectness, imprecision, publication bias) rather than a full formal GRADE assessment with separate domain scoring. CF: Cystic fibrosis; ECMO: Extracorporeal membrane oxygenation; ICU: Intensive care unit; TXA: Tranexamic acid.

Data synthesis and analysis

Because of marked clinical and methodological heterogeneity, meta-analysis was not performed. This decision was made after data extraction, not because of an absence of clinically relevant studies, but because the available studies were not estimating the same treatment effect. Combining a placebo-controlled trial in stable non-massive haemoptysis with retrospective intensive care unit (ICU) cohorts, paediatric extracorporeal membrane oxygenation (ECMO) series, cystic fibrosis pathway studies, and administrative database analyses would have obscured the clinical meaning of the results.

Findings were therefore synthesised narratively. Results are presented first by pre-specified outcome (bleeding cessation/haemostasis, mortality, recurrence, need for invasive procedures, length of stay, and adverse events), and these outcome-level findings are then interpreted according to age group, clinical setting, route of administration, and study design. Adult and paediatric data were considered separately where appropriate. Emergency department and ward-based studies were interpreted separately from intensive care studies, given the major differences in baseline risk and treatment indication. Route-specific effects were also examined, particularly nebulised or inhaled therapy compared with systemic administration. The synthesis focused on consistency of direction of effect, clinical plausibility, risk of bias, and whether observed outcomes were likely to reflect the intervention itself or the severity of the underlying illness.

RESULTS

The database search identified 642 records. After duplicate removal, 532 titles and abstracts were screened, and 69 full-text articles were assessed for eligibility. Ten studies met the inclusion criteria and were included in the final narrative synthesis. The study selection process is shown in the PRISMA flow diagram (Figure 1).

Figure 1  PRISMA flow diagram of study identification, screening, eligibility assessment, and inclusion.

The included studies were clinically diverse. They comprised three randomised trials, several retrospective or observational cohort studies, one before-and-after pathway study, and one small case series. Sample size ranged from three critically ill adults in a case series to 28539 emergency admissions in a national inpatient database. The main characteristics of the included studies are shown in Table 3.

Table 3 Characteristics of included studies evaluating antifibrinolytic therapy for haemoptysis and pulmonary haemorrhage.

Ref.	Study design	Population and setting	Indication/scenario	Agent	Route	Dose/regimen	Comparator	Outcomes assessed	Key results	Safety and limitations
Al-Samkari et al[16], 2019, United States	Before-after pathway study	Adults with cystic fibrosis; inpatient and outpatient care (n = 21; 72 episodes)	Haemoptysis in cystic fibrosis	Tranexamic acid or epsilon-aminocaproic acid	Systemic (oral/IV)	Pathway-defined; oral or IV according to episode	Pre-enrolment period in the same patients	Bleeding cessation time; haemoptysis-related admissions; adverse events	Median time to bleeding cessation was 2 days; annualised admissions decreased by 50% (2.44 to 1.23 per patient-year; P = 0.0024)	One catheter-associated upper-extremity DVT; otherwise well tolerated. Cystic fibrosis-specific, uncontrolled, small sample
Alabdrabalnabi et al[20], 2020, Saudi Arabia	Case series	Critically ill adults with significant haemoptysis in ICU (n = 3)	Recurrent or persistent haemoptysis	Tranexamic acid	Nebulised	500 mg three times daily	None	Symptom improvement; transfusion requirement	All patients improved, with reduced transfusion need and discharge after symptom resolution	Well tolerated. Very small heterogeneous case series
Alkazemi et al[21], 2023, United States	Retrospective matched cohort	Adult inpatients with haemoptysis, 2018-2021 (n = 14 TXA; 58 controls)	Moderate-to-massive haemoptysis	Tranexamic acid	Nebulised	Per institutional practice	Conventional management without TXA	Need for invasive intervention; resolution; recurrence; LOS	No significant difference in invasive intervention (35.7% vs 56.9%; P = 0.344); similar resolution, recurrence, and LOS	No specific adverse events reported. Small TXA cohort; retrospective; limited power
Bellam et al[22], 2016, India	Single-blind RCT	Adults with sub-massive haemoptysis (n = 66)	Sub-massive haemoptysis	Tranexamic acid	Intravenous	1 g loading dose, then 1 g over 8 hours infusion	IV normal saline placebo	Frequency; quantity; VAS score; intervention; transfusion; LOS	VAS improved (P = 0.001); fewer interventions (16% vs 38%; P = 0.053); lower volume/frequency; shorter LOS, not statistically significant	No adverse events. Pilot size; limited power
Bethuel et al[5], 2025, United States	Retrospective multicentre analysis	Adults hospitalised with haemoptysis across three tertiary hospitals (n = 488; 96 received TXA)	All-cause haemoptysis in critically and non-critically ill patients	Tranexamic acid	Nebulised	Per clinician decision	Supportive care only	ICU/hospital LOS; ventilation; bronchoscopy; mortality	Higher crude mortality; propensity-adjusted OR for death with TXA 2.51 (95%CI: 1.56-4.02)	Possible indication bias and safety signal. Retrospective design; confounding by severity
Gopinath et al[4], 2023, India	Open-label RCT	Adults with active non-massive haemoptysis in the ED (n = 110)	Acute non-massive haemoptysis	Tranexamic acid	Nebulised vs IV	500 mg three times daily	Alternative route: Nebulised vs IV	Cessation at 30 minutes; bleeding amount; BAE; discharge; adverse events	30-minute cessation higher with nebulised TXA (40 vs 28; P = 0.0019); less BAE (13 vs 21; P = 0.024); higher discharge (68% vs 39%; P = 0.005)	Two asymptomatic bronchoconstriction episodes, resolved. Single-centre; non-massive cases only
Kinoshita et al[17], 2019, Japan	Nationwide retrospective propensity-matched cohort	Emergency admissions for haemoptysis, 2010-2017 (n = 28539; 9933 matched pairs)	Haemoptysis requiring emergency admission	Tranexamic acid	Intravenous	On admission day	No TXA	In-hospital mortality; LOS; cost	Mortality 9.0% vs 11.5% (risk difference -2.5%; 95%CI: -3.5 to -1.6); shorter LOS (-2.4 days); lower costs	Adverse events not reported. Administrative database; residual unmeasured confounding
O'Neil et al[18], 2020, United States	Retrospective observational study	Paediatric ICU patients aged 0-18 years with pulmonary haemorrhage (n = 19)	Pulmonary haemorrhage	Tranexamic acid	Inhaled or endotracheal	Varied dosing	None	Cessation of bleeding; adverse events	Bleeding cessation in 18/19 patients (95%)	No major adverse events observed. Small, single-centre study; no comparator
Singleton et al[19], 2023, United States	Retrospective cohort	Paediatric ECMO patients with pulmonary haemorrhage (n = 53)	Pulmonary haemorrhage during ECMO	Tranexamic acid	Inhaled	Per institutional protocol	None	Change in bleeding scale; cessation within 48 hours; adverse events	Bleeding cessation in 48/53 patients (91%) within 48 hours; no adverse events reported	No adverse effects reported. Retrospective; ECMO-specific population
Wand et al[15], 2018, Israel	Double-blind RCT	Adults admitted with non-massive haemoptysis (n = 47)	Non-massive haemoptysis	Tranexamic acid	Nebulised	500 mg three times daily	Placebo (normal saline)	Resolution by day 5; LOS; invasive procedures; recurrence	Resolution 96% vs 50% (P < 0.0005); LOS 5.7 days vs 7.8 days (P = 0.046); invasive procedures 0% vs 18% (P = 0.041); lower 1-year recurrence (P = 0.009)	No side effects. Small sample; excluded massive bleeds

Studies are presented in alphabetical order by first author; the Population and setting column explicitly states whether each study enrolled adult or paediatric patients, and adult and paediatric studies are interpreted separately throughout the Results and Discussion. Baseline demographic detail and severity criteria were reported with varying completeness across the primary studies; where a field was not reported in the source publication, this is reflected by its absence from the corresponding cell rather than by an assumed value. BAE: Bronchial artery embolisation; DVT: Deep vein thrombosis; ECMO: Extracorporeal membrane oxygenation; ED: Emergency department; ICU: Intensive care unit; IV: Intravenous; LOS: Length of stay; OR: Odds ratio; RCT: Randomised controlled trial; TXA: Tranexamic acid; VAS: Visual analogue scale.

Study characteristics and clinical heterogeneity

The included studies differed substantially in design, setting, population, route of TXA administration, and outcome reporting. This heterogeneity was clinically important, not merely statistical. Some trials enrolled stable adults with non-massive haemoptysis, generally in emergency department or ward settings, where the goal of treatment was early bleeding control and avoidance of escalation[4,15]. In contrast, other studies included patients already admitted to intensive care, in whom haemoptysis occurred alongside respiratory failure, infection, anticoagulation exposure, malignancy, or severe comorbidity[5]. These are not interchangeable populations. The underlying causes of bleeding also varied: One study focused on adults with cystic fibrosis[16], while others included mixed populations with bronchiectasis, infection, malignancy, iatrogenic bleeding, or anticoagulation-associated haemoptysis[15,17]. Tranexamic acid may help stabilise clot formation and reduce short-term airway bleeding, but it does not treat the underlying lesion, nor does it replace definitive source control when embolisation, bronchoscopy, or surgery is required.

Haemostasis and bleeding cessation

Bleeding cessation was the most consistently reported primary outcome and showed the clearest signal of benefit. In the double-blind placebo-controlled trial by Wand et al[15], nebulised TXA was associated with higher rates of complete resolution by day 5 in adults with non-massive haemoptysis. In the open-label randomised trial by Gopinath et al[4], nebulised TXA achieved superior early bleeding cessation at 30 minutes compared with intravenous TXA. In the paediatric intensive care cohort, inhaled or endotracheal TXA was associated with cessation of pulmonary haemorrhage in 18 of 19 patients[18], and in children receiving extracorporeal membrane oxygenation, inhaled TXA was associated with bleeding cessation in 48 of 53 patients within 48 hours[19]. In the cystic fibrosis pathway study, median time to bleeding cessation was 2 days[16]. Across study designs, the direction of effect for bleeding cessation was consistently favourable with local (nebulised, inhaled, or endotracheal) TXA; this consistency was strongest in stable adult non-massive haemoptysis and feasibility-level in the higher-acuity paediatric and ECMO cohorts[20].

Mortality

Mortality was the second primary outcome and showed the most striking inconsistency in the evidence base, which is interpreted here primarily through the lens of setting and confounding by indication. In the large Japanese nationwide propensity-matched cohort of emergency admissions for haemoptysis, intravenous TXA given on the day of admission was associated with lower in-hospital mortality (9.0% vs 11.5%)[17]. In contrast, a multicentre retrospective analysis of 488 hospitalised adults reported higher adjusted mortality among patients receiving nebulised TXA, with a propensity-adjusted odds ratio for death of 2.51 (95%CI: 1.56-4.02)[5]. These two findings point in opposite directions and should not be averaged or treated as conflicting evidence about a single causal effect. The Japanese cohort reflects systemic TXA use across a broad, largely lower-acuity emergency admission population, captured through an administrative dataset that cannot fully resolve bleeding severity or the reason for treatment. The retrospective cohort reflects nebulised TXA use that was concentrated in more severely or persistently bleeding patients, including critically ill patients, in whom the drug is more likely to have been a marker of severity than a cause of death. Mortality findings are therefore considered observational associations only, and are not interpreted as evidence that TXA causes or prevents death in either direction.

Recurrence

Recurrence was reported in only a minority of studies. In the placebo-controlled trial by Wand et al[15], nebulised TXA was associated with lower recurrence of haemoptysis at one year. In the cystic fibrosis pathway study, annualised haemoptysis-related admissions decreased by 50% (from 2.44 to 1.23 per patient-year) after introduction of an antifibrinolytic pathway[16]. In a smaller matched retrospective cohort, recurrence did not differ significantly between nebulised TXA and standard care, although the treated sample was small[21]. Recurrence data therefore favour TXA as part of a structured pathway, but the evidence is sparse and largely uncontrolled.

Need for invasive procedures

Need for bronchoscopy, bronchial artery embolisation, or other invasive intervention was reduced in both randomised trials of local TXA: Wand et al[15] reported fewer invasive procedures (0% vs 18%), and Gopinath et al[4] reported less need for bronchial artery embolisation with nebulised compared with intravenous TXA (13 vs 21 patients). In the smaller Indian trial of intravenous TXA for sub-massive haemoptysis, there was a numerical reduction in invasive intervention that did not reach statistical significance (16% vs 38%; P = 0.053)[22]. A retrospective matched cohort found no significant difference in need for invasive intervention between nebulised TXA and conventional management (35.7% vs 56.9%; P = 0.344), but this comparison was underpowered[21].

Length of stay

Length of stay favoured nebulised TXA in the trial by Wand et al[15] (5.7 days vs 7.8 days; P = 0.046) and was numerically shorter in the small Indian trial without reaching significance[22]. In the Japanese nationwide cohort, intravenous TXA was associated with a shorter hospital stay (-2.4 days) alongside lower costs[17]. The smaller matched retrospective cohort found no significant difference in length of stay[21].

Adverse events

Across all ten included studies, reported adverse events were uncommon, but the type, incidence, severity, and attribution of events varied by study and are summarised here systematically rather than incidentally. Two episodes of asymptomatic bronchoconstriction were reported in the trial by Gopinath et al[4], both resolving without clinical deterioration. In the cystic fibrosis pathway study, one catheter-associated upper-extremity deep vein thrombosis occurred in a patient with pre-existing thrombotic risk, and was not clearly attributed to antifibrinolytic therapy[16]. No adverse events were reported in the double-blind trial by Wand et al[15] or the single-blind trial by Bellam et al[22]. No major adverse events were reported in the paediatric intensive care cohort[18] or the paediatric ECMO cohort[19]. Adverse events were not systematically reported in the Japanese nationwide cohort[17] or the retrospective matched cohort by Alkazemi et al[21]. Taken as a whole, the only clearly drug-attributable adverse events were transient, asymptomatic bronchoconstriction with nebulised therapy; the single thrombotic event occurred in a patient with independent thrombotic risk factors and attribution to TXA is uncertain. However, the absence of frequent reported harm should not be interpreted as evidence of safety. Most included studies were small, retrospective, or otherwise not designed or powered to systematically capture thromboembolism, bronchospasm, airway clot burden, or delayed complications, and several did not report adverse events at all. The true incidence of these complications with TXA in haemoptysis is therefore unknown rather than low.

Interpretation by setting, route, and population

Having summarised each outcome, the following section interprets these findings according to clinical setting, route of administration, and population, since the direction and strength of effect for every outcome above varied systematically along these lines. Seven studies evaluated antifibrinolytic therapy in adults with haemoptysis, and three in paediatric or paediatric critical care settings. In stable adults with non-massive haemoptysis in emergency department or ward settings, nebulised TXA was associated with faster bleeding control, shorter length of stay, and fewer invasive interventions, with the most internally consistent evidence of all the clinical contexts examined[4,15]. Intravenous TXA in this same stable population showed improvement in bleeding scores and frequency in a small single-blind trial, although the reduction in invasive procedures did not reach conventional statistical significance[22].

In ICU-level haemoptysis, the picture is far less consistent. The Japanese nationwide cohort suggested a favourable association between intravenous TXA and in-hospital outcomes in a broad emergency admission population that included but was not limited to critical illness[17], whereas the multicentre retrospective cohort of critically and non-critically ill adults reported higher adjusted mortality with nebulised TXA[5]. As discussed under Mortality above, this discrepancy is most plausibly explained by confounding by indication rather than by a true difference in drug effect between routes: Nebulised TXA in this cohort was disproportionately used in patients with more severe or persistent bleeding and worse respiratory status. A smaller matched cohort found no significant difference between nebulised TXA and standard care in invasive intervention, resolution, recurrence, or length of stay, but the treated sample was small[21].

In cystic fibrosis, antifibrinolytic therapy embedded within a structured pathway was associated with reduced haemoptysis-related admissions and was generally well tolerated, although the before-and-after design cannot exclude secular trends or other concurrent changes in care[16].

In paediatric pulmonary haemorrhage and paediatric ECMO-associated pulmonary haemorrhage, inhaled or endotracheal TXA was associated with high rates of bleeding cessation and few reported adverse events[18,19]. These cohorts are important because they include high-risk, anticoagulated patients, but they remain retrospective, uncontrolled, and exposed to strong competing risks (severe respiratory disease, extracorporeal support, and competing causes of death); their findings support feasibility and short-term tolerability more strongly than causal efficacy, and do not define optimal dosing, duration, or patient selection. No study in this review enrolled exclusively paediatric non-critically-ill patients, so adult and paediatric evidence cannot be compared directly outcome-by-outcome; paediatric data are accordingly reported separately rather than pooled with adult findings throughout this section and in Table 3.

Only one randomised trial directly compared nebulised with intravenous TXA for the same indication. In that study, nebulised therapy was associated with faster cessation of bleeding, fewer bronchial artery embolisations, and greater likelihood of discharge from the emergency department than intravenous therapy[4]. Across the wider evidence base, nebulised or inhaled administration appears attractive because it delivers the drug directly to the airway surface while limiting systemic exposure. Systemic administration has a potential role, particularly where inhaled delivery is impractical or bleeding is diffuse, but the balance between haemostatic benefit and thrombotic risk remains less clear, and route selection should be guided by clinical context rather than by a single uniform rule[17,22].

Risk of bias assessment

Risk of bias assessment is summarised in Figures 2 and 3 and at study level, with domain-specific justifications, in Table 1. The traffic-light plot demonstrates that several studies had at least one domain at serious or critical risk of bias, particularly in relation to confounding, participant selection, and deviations from intended interventions (Figure 2). The summary plot similarly shows that overall risk of bias was driven mainly by observational designs, non-standardised treatment allocation, and incomplete control for baseline severity (Figure 3).

Figure 2  Risk of bias traffic-light plot for included studies.

Figure 3  Summary risk of bias plot across included studies.

The risk of bias pattern explains much of the apparent inconsistency in the evidence, particularly the divergent mortality findings described above. Randomised trials in stable emergency department or ward patients were more likely to show benefit because their outcomes—early bleeding cessation, bleeding volume, discharge, and need for intervention—are directly sensitive to short-term haemostatic control[4,15]. ICU-based observational studies were more vulnerable to confounding by indication, because TXA was often given to patients with more severe bleeding or clinical deterioration[5]. In such cohorts, mortality is strongly shaped by baseline physiological reserve, respiratory failure, malignancy, sepsis, and anticoagulation status. Tranexamic acid may therefore be a marker of severity rather than the cause of worse outcome.

Certainty of evidence

A simplified GRADE-informed certainty assessment for the main outcomes is provided in Table 2. Certainty of evidence is highest, although still limited overall, for nebulised TXA improving bleeding cessation, length of stay, and need for invasive procedures in stable, non-massive adult haemoptysis, where two randomised trials show a consistent direction of effect with a plausible mechanism and modest imprecision from small sample sizes. Certainty is very low for effectiveness and safety outcomes in ICU-level haemoptysis, paediatric pulmonary haemorrhage, and ECMO-associated pulmonary haemorrhage, reflecting serious risk of bias from confounding by indication and selection, small numbers of uncontrolled or retrospective studies, and indirectness between the populations studied and any broader haemoptysis population. Certainty for mortality outcomes specifically is very low in all settings, given the directly conflicting observational signals described above.

Taken together, the evidence might support TXA as a potentially useful adjunct in selected patients, particularly by inhaled or nebulised routes in non-massive haemoptysis. It does not support TXA as a stand-alone therapy for severe haemoptysis, nor does it justify delaying airway control, bronchoscopy, embolisation, or treatment of the underlying cause.

DISCUSSION

This review suggests that TXA has a plausible and clinically useful role in haemoptysis, but only if it is understood as an adjunct rather than a definitive treatment. The most consistent benefit was seen in stable patients with non-massive haemoptysis, particularly when TXA was delivered directly to the airway by nebulised or inhaled routes[4,15]. In this setting, the aim is not to “cure” haemoptysis, but to reduce active bleeding, improve airway clearance, avoid escalation when possible, and allow time for diagnosis and treatment of the underlying cause. This distinction is important. Haemoptysis is not one disease. It is a final common presentation of many different processes, including bronchiectasis, malignancy, infection, cystic fibrosis, vasculitis, iatrogenic injury, anticoagulation, and diffuse pulmonary bleeding syndromes[23,24]. It is therefore unlikely that one haemostatic intervention will have the same effect across all clinical phenotypes.

The central threat in clinically significant haemoptysis is often respiratory rather than haemodynamic. Blood within the airways can obstruct ventilation, impair gas exchange, and precipitate respiratory failure even when total blood loss is not large. This explains why airway protection, patient positioning, oxygenation, bronchoscopy, and timely source control remain fundamental. Older but important experience with rigid bronchoscopy and cold saline lavage already showed that controlling airway flooding may be lifesaving in massive haemoptysis[25]. Contemporary management has evolved, but the principle remains unchanged: Death is often driven by airway flooding rather than exsanguination. TXA can support clot stability, but it does not remove obstructing clot, localise the bleeding source, treat infection or tumour, or replace bronchial artery embolisation when this is required.

The available evidence fits this clinical logic. In the placebo-controlled trial by Wand et al[15], inhaled TXA improved bleeding resolution, reduced hospital stay, and decreased need for invasive procedures in adults with non-massive haemoptysis. Similarly, Gopinath et al[4] found that nebulised TXA achieved faster early bleeding cessation than intravenous TXA and was associated with fewer bronchial artery embolisations and more emergency department discharges. These findings support local therapy as a pragmatic option in stable patients, particularly when the objective is early haemostatic control while investigations and cause-directed treatment proceed. The results also support the biological appeal of airway delivery: A high local drug concentration at the bleeding surface with less systemic exposure.

However, the evidence should not be stretched beyond the populations studied. Patients with haemodynamic instability, severe respiratory compromise, or immediate need for airway or procedural intervention were generally excluded from the most favourablerandomised trials[4,15]. This limits generalisability to life-threatening haemoptysis. In severe disease, TXA may still be reasonable as a temporising measure, but it should never delay bronchoscopy, embolisation, airway control, reversal of coagulopathy, antimicrobial therapy, or oncological/interventional management where indicated. This is where the literature can be misleading if read superficially. Positive trial results in stable emergency department populations cannot simply be transferred to ICU patients with respiratory failure, sepsis, malignancy, or anticoagulation-related bleeding.

This caution is reinforced by the conflicting adult observational data. The large Japanese administrative cohort found that intravenous TXA given on the day of admission was associated with lower in-hospital mortality and shorter length of stay[17]. The scale of this study is impressive, but administrative datasets cannot fully capture bleeding severity, physiological instability, airway compromise, timing of intervention, or the reason why a clinician decided to give TXA. Conversely, Bethuel et al[5] reported higher adjusted mortality among patients receiving nebulised TXA in a multicentre cohort of hospitalised adults. This signal should be respected, but not interpreted simplistically as proof of harm. In real clinical practice, TXA is often used when bleeding is more severe, persistent, or clinically concerning. Confounding by indication is therefore highly plausible. In such patients, mortality may reflect the severity of the underlying disease rather than the drug itself.

The same issue applies to critical care and extracorporeal support. Paediatric ICU and ECMO studies reported high rates of bleeding cessation with inhaled or endotracheal TXA and few reported adverse events[18,19]. These are encouraging findings, particularly because systemic anticoagulation and severe respiratory disease make pulmonary haemorrhage difficult to manage in ECMO. Case-based literature also illustrates how severe pulmonary bleeding may require extraordinary supportive strategies, including airway isolation and extracorporeal support, rather than pharmacological therapy alone[26]. Still, the paediatric evidence remains retrospective, uncontrolled, and exposed to strong competing risks. In this context, TXA may help stabilise airway bleeding, but outcomes are still driven by the underlying cardiopulmonary disease, anticoagulation intensity, and the ability to maintain oxygenation and ventilation.

Cystic fibrosis represents another important phenotype. In the before-and-after pathway study by Al-Samkari et al[16], antifibrinolytic therapy was associated with reduced haemoptysis-related admissions and generally good tolerability. This is clinically relevant because cystic fibrosis-associated haemoptysis often recurs, occurs in structurally abnormal airways, and may require repeated hospitalisation or embolisation. The study does not prove causality, but it supports the idea that TXA may be most useful when embedded within a structured pathway rather than used as an isolated rescue treatment. It also highlights a broader point: Recurrent haemoptysis may require a plan for repeated episodes, not only acute reaction to the current bleed.

Safety remains difficult to define. Across the included studies, reported adverse events were uncommon. Bronchospasm was rare and transient in the randomised trial comparing nebulised with intravenous TXA[4]. A catheter-associated upper-extremity thrombosis occurred in the cystic fibrosis pathway study, but in a patient with pre-existing risk factors, making attribution uncertain[16]. Paediatric inhaled TXA studies did not identify major safety concerns[18,19]. Nevertheless, the absence of frequent reported harm is not the same as proven safety. Most studies were small, retrospective, or not designed to detect thrombotic complications, bronchospasm, airway clot burden, or delayed adverse events.

The wider antifibrinolytic literature is reassuring in some respects but cannot be directly imported into haemoptysis. In major trauma, CRASH-2 showed that TXA reduced death due to bleeding without a clear excess of vascular occlusive events when used appropriately[26]. Individual patient-level analyses have also suggested that early administration is important in acute severe bleeding, with diminishing benefit and possible loss of effect when treatment is delayed[27-30]. Perioperative and surgical literature supports the haemostatic efficacy of antifibrinolytics in reducing blood loss and transfusion requirements[6,28,31-34]. Yet pulmonary bleeding is different. In haemoptysis, clot formation occurs inside an organ responsible for gas exchange. A clot can be beneficial at the bleeding point and dangerous if it obstructs the airway. This is why route, dose, patient selection, and monitoring matter more here than in many other bleeding scenarios.

Older and smaller haemoptysis-specific studies already suggested potential benefit from antifibrinolytic therapy, but also showed why conclusions remain fragile. Tscheikuna et al[35] reported experience with TXA in haemoptysis, while later reviews concluded that antifibrinolytics may reduce bleeding but that evidence remained limited by small sample sizes, heterogeneity, and inconsistent endpoints[29,31]. Reports of inhaled or endobronchial TXA, including early airway-directed experiences, further support biological plausibility and practical feasibility[32,34]. Bronchoscopic adjuncts, including cryoprobe-assisted clot extraction, may also be necessary when airway obstruction rather than active bleeding is the immediate problem[33]. These studies collectively support TXA as part of haemoptysis care, but not as the centre of care.

The pharmacological plausibility of antifibrinolytic therapy is further supported by efficacy in non-pulmonary bleeding, including trauma, surgical, and obstetric haemorrhage; this indirect evidence is noted here only briefly, as it cannot define the role of TXA in haemoptysis, where clot formation occurs inside the airway and may both control bleeding and worsen obstruction. This review can be compared directly with two previous syntheses of antifibrinolytic therapy for haemoptysis. The 2016 Cochrane review by Prutsky et al[30] identified only three eligible randomised trials and concluded that evidence was insufficient to recommend antifibrinolytic therapy for haemoptysis of any cause; the present review extends this earlier work by incorporating the subsequently published randomised trials by Gopinath et al[4] and a substantially larger body of observational evidence across adult, paediatric, ICU, cystic fibrosis, and ECMO populations that did not yet exist at the time of the Cochrane review. The narrative review by Gadre and Stoller[29] similarly concluded that TXA may reduce bleeding but that evidence remained limited by small sample sizes and heterogeneity; the present review adds incremental value by applying a systematic, PRISMA 2020-based search and selection process, by separating effectiveness and safety findings according to clinical setting and route of administration rather than treating haemoptysis as a single entity, and by explicitly identifying confounding by indication as the most probable explanation for the divergent mortality findings that have emerged in more recent observational cohorts not available to earlier reviewers.

In practical terms, therefore, this review supports a route- and severity-based approach. For stable patients with mild to moderate haemoptysis, nebulised TXA is a reasonable adjunct when there is ongoing bleeding, patient discomfort, concern for progression, or delay while imaging and definitive planning are arranged. A commonly studied regimen is 500 mg two or three times daily, although optimal dosing and duration remain undefined[4,15]. For more severe bleeding, TXA may be used, but only alongside escalation: Senior review, airway planning, bronchoscopy when appropriate, correction of coagulopathy, and early consideration of bronchial artery embolisation. For systemic TXA, the threshold should be more cautious, particularly in malignancy, previous thrombosis, cardiovascular disease, or complex anticoagulation decisions. In these patients, the potential haemostatic gain must be balanced against thrombotic risk and against the possibility that systemic therapy offers less local airway effect than inhaled treatment.

The major limitation of the current evidence is not simply that studies are few. It is that they answer different questions. A trial in stable non-massive haemoptysis asks whether TXA can shorten bleeding and reduce escalation. An ICU cohort asks whether TXA changes outcomes in patients whose mortality is driven by respiratory failure, infection, malignancy, or multiorgan dysfunction. A paediatric ECMO series asks whether inhaled TXA is feasible in a highly specialised population receiving anticoagulation. These should not be pooled into a single number. This is why meta-analysis was not appropriate for this review. A pooled estimate would have looked precise, but would not have been clinically honest.

Future studies should therefore be designed around phenotype rather than around haemoptysis as a single entity. Trials should separate non-massive, moderate, and life-threatening haemoptysis using functional definitions that include oxygenation, airway compromise, haemodynamic status, transfusion, need for ventilation, and need for urgent bronchoscopy or embolisation. They should stratify by cause, especially bronchiectasis, cystic fibrosis, malignancy, infection, iatrogenic bleeding, and anticoagulation-related bleeding. They should also compare route-specific strategies directly, including nebulised, endobronchial/topical, and intravenous TXA, using standardised dosing and clinically meaningful endpoints. Bleeding cessation alone is not enough. Future outcomes should include recurrence, need for bronchoscopy, need for embolisation, mechanical ventilation, ICU admission, length of stay, readmission, thromboembolism, bronchospasm, airway clot burden, and mortality.

Limitations

It is a narrative synthesis and does not provide pooled estimates of effect. The evidence base is small and heterogeneous, and many included studies are retrospective. English-language restriction may have introduced language bias. Publication bias is also possible, particularly among small case series reporting favourable outcomes. However, the review also has strengths. It brings together adult, paediatric, emergency, ward, ICU, cystic fibrosis, and ECMO data, while interpreting them according to clinical context and route of administration rather than treating all TXA exposure as equivalent. The main conclusion is deliberately cautious: TXA appears useful for early haemostatic control in selected patients, especially by inhaled or nebulised routes, but it should remain an adjunct within a structured haemoptysis pathway. It should not replace the fundamentals: Protect the airway, stabilise physiology, identify the source, and treat the cause.

CONCLUSION

Tranexamic acid appears to be a useful adjunct for short-term haemostatic control in selected patients with haemoptysis, particularly when delivered directly to the airway by nebulised, inhaled, topical, or endobronchial routes. The most consistent evidence supports its use in stable patients with non-massive haemoptysis, where early bleeding control may reduce escalation, shorten admission, and allow time for definitive investigation and treatment of the underlying cause. Even in this setting, the certainty of evidence is best described as low rather than high, and certainty for effectiveness and safety outcomes in ICU, paediatric, and ECMO populations is very low.

Evidence in severe haemoptysis, ICU populations, and patients with major physiological instability remains uncertain, largely because treatment is often given to the sickest patients and outcomes are strongly influenced by respiratory failure, malignancy, infection, anticoagulation, and baseline cardiopulmonary reserve. TXA should therefore not be viewed as definitive therapy for pulmonary haemorrhage. It should not delay airway protection, bronchoscopy, bronchial artery embolisation, correction of reversible coagulopathy, or source-directed management. Future studies should move beyond haemoptysis as a single entity and evaluate TXA according to bleeding severity, route of administration, underlying aetiology, and clinical setting, using standardised endpoints that include recurrence, need for intervention, respiratory deterioration, thromboembolic events, airway complications, and mortality.

ACKNOWLEDGEMENTS

We extend our appreciation to the Faculty of Life Sciences and Education at the University of South Wales, in partnership with Learna Ltd., for the Acute Medicine MSc program and their invaluable support in our work.