The Integrated Hemostatic Network in Pediatric ECMO: A Systems-Level Framework for Precision Hemostasis

Pediatric extracorporeal membrane oxygenation (ECMO) is associated with complex hemostatic disturbances arising from interactions among blood-circuit interfaces, developmental hemostasis, endothelial dysfunction, coagulation, fibrinolysis, inflammation, and disease- and treatment-related factors. Conventional approaches focused on individual laboratory abnormalities may not adequately capture this complexity. This review proposes the Integrated Hemostatic Network (IHN) as a unified conceptual framework for understanding ECMO-associated dyshemostasis and informing precision hemostatic management. This narrative review synthesized literature identified iteratively through PubMed searches addressing pediatric ECMO hemostasis and related mechanistic and clinical domains. Priority was given to pediatric studies, prospective comparative studies, randomized trials, systematic reviews, and consensus or guideline documents. Adult and non-ECMO evidence was considered when relevant pediatric data were limited. The evidence was integrated across developmental hemostasis, blood-circuit interactions, platelet and von Willebrand factor biology, coagulation and anticoagulant pathways, fibrinolysis, endothelial dysfunction, inflammation, complement activation, and hemolysis, with implications for multimodal monitoring and individualized management. The evidence supports a systems-level interpretation of pediatric ECMO-associated dyshemostasis, in which interacting determinants evolve over time. Bleeding, thrombosis, and their coexistence may arise from overlapping disturbances rather than isolated abnormalities or anticoagulation intensity alone. Three proposed working hemostatic states-bleeding-predominant, thrombosis-predominant, and mixed bleeding-thrombotic-provide a conceptual structure for clinical assessment and therapeutic reasoning but are not validated biological categories, prediction models, or treatment algorithms. The IHN integrates developmental and clinical context, laboratory and functional assessment, anticoagulant effects, and patient and circuit findings to support longitudinal interpretation beyond isolated laboratory targets. By explicitly integrating these interacting determinants and their temporal evolution, the IHN provides a unified conceptual architecture for understanding pediatric ECMO-associated dyshemostasis. Its clinical utility requires prospective multicenter evaluation to establish reproducibility and determine whether its application improves patient-centered outcomes.