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.

Keywords: 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.