Local Intrapulmonary Hemostatic Therapies for Pediatric Pulmonary Hemorrhage: A Systematic Review and Meta-Analysis.

Abstract

Pediatric pulmonary hemorrhage, including diffuse alveolar hemorrhage and severe hemoptysis, is a life-threatening condition associated with high morbidity and mortality. Management is largely supportive, and systemic hemostatic agents may be limited by thrombotic risk. Local intrapulmonary hemostatic therapies, such as tranexamic acid (TXA) and recombinant activated factor VII (rFVIIa), have emerged as targeted strategies to control bleeding while minimizing systemic exposure. However, the available evidence remains fragmented. We conducted a systematic review and meta-analysis in accordance with PRISMA 2020 guidelines and a prospectively registered PROSPERO protocol (CRD420251273408). PubMed/MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library were searched from inception to the final search date. Studies including children (0-18 years) with pulmonary hemorrhage treated with local intrapulmonary TXA, rFVIIa, or combination therapy were eligible. Primary outcomes were bleeding control and safety. Random-effects meta-analyses of pooled proportions were performed where feasible. Six studies comprising 111 pediatric patients met the inclusion criteria, of which five were included in quantitative synthesis. TXA-based local therapy achieved a pooled bleeding control rate of 86.6% (95% CI: 63.9%-95.9%) with moderate heterogeneity, while intrapulmonary rFVIIa achieved a pooled bleeding control rate of 82.5% (95% CI: 62.9%-93.0%) with low heterogeneity. No statistically significant difference was observed between therapies. Recurrence of hemorrhage and transfusion requirements were variably reported but appeared reduced following successful bleeding control. No consistent signal of treatment-related thromboembolic complications was identified, including among oncology/hematopoietic cell transplantation and extracorporeal membrane oxygenation-supported patients. Local intrapulmonary hemostatic therapies with TXA or rFVIIa are associated with high rates of bleeding control in pediatric pulmonary hemorrhage and appear to be safe adjunctive options in critically ill children. Given the predominance of small observational studies and heterogeneous populations, prospective multicenter studies are needed to define optimal patient selection, dosing strategies, and safety profiles and to clarify the role of these therapies within stepwise management algorithms.