Extracorporeal Membrane Oxygenation (ECMO) is associated with high risks of bleeding and clotting. While traditional anticoagulants like heparin and bivalirudin target the coagulation cascade, prostaglandins including PGE₁ and PGI₂ may offer adjunctive platelet inhibition. This study evaluated whether prostaglandin use modifies the risk of severe bleeding or clotting events in pediatric ECMO patients.

We used the Pediatric Health Information System database from 2004 to 2025, and included children supported with ECMO. Primary outcomes were severe bleeding and clotting events. Generalized linear mixed model regressions adjusted for site, patient and ECMO data, and pulmonary hypertension.

A total of 22,061 pediatric ECMO patients were included. Pulmonary hypertension was present in 12.4% (2736/22,061). PGE₁ and PGI₂ were independently associated with increased risk of pulmonary hemorrhage (PGE₁: adjusted OR 1.24, P = .003; PGI₂: adjusted OR 1.21, P = .047). Conversely, neither PGE₁ nor PGI₂ were independently associated with intracranial hemorrhage (PGE₁: adjusted OR 1.01, P = .92; PGI₂: adjusted OR 0.96, P = .79), stroke (PGE₁: adjusted OR 1.02, P = .84; PGI₂: adjusted OR 0.88, P = .38), or other bleeding or thrombotic events.

In this large multicenter cohort of more than 22,000 pediatric ECMO patients, neither PGE₁ nor PGI₂-modulated anticoagulation conferred measurable protection against the major bleeding or clotting complications.