PROJECT SUMMARY Due to coagulopathy and thrombocytopenia induced by hemodilution and the extracorporeal circuit itself, children supported by extracorporeal membrane oxygenation (ECMO) are at significant risk of bleeding. In order to prevent bleeding, pediatric intensivists often prescribe prophylactic platelet transfusions. However, in observational studies, prophylactic platelet transfusions to children on ECMO have been independently associated with increased thrombosis, mortality, and paradoxically, increased bleeding. Guidelines to direct platelet transfusions in this patient population are limited by the lack of evidence and therefore based on expert opinion alone. Given the significant associated risks, it is crucial to provide evidence to guide clinicians. The ECmo hemoSTAtic Transfusions In Children (ECSTATIC) pilot trial, endorsed by BloodNet, PediECMO, the Extracorporeal Life Support Organization (ELSO) and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI), will be conducted in ten sites. Non-bleeding children 0-18 years of age will be randomized 1:1 to either a platelet transfusion threshold of 90 (liberal transfusion strategy) or 50 x109/L (restrictive transfusion strategy). They will be followed until they progress to severe bleeding or thrombosis, they are decannulated from ECMO or they reach 21 days. In this pilot, we will test the separation between the restrictive and liberal transfusion strategies, the feasibility of patient enrollment, and the ability of an adjudication committee to determine the severity of bleeding and thrombotic outcomes. The proposed pilot trial is innovative in that it is focused on children supported by ECMO, a population in whom transfusion strategies have never been tested previously; it involves the largest separation between the two arms of any platelet transfusion trial conducted in the past; and it involves two newly developed definitions of bleeding and thrombosis particularly applicable to children supported by ECMO. The R34 pilot trial will provide necessary and sufficient information to proceed with the definitive ECSTATIC RCT to evaluate the impact of a restrictive prophylactic platelet transfusion threshold on the clinical outcomes in children on ECMO. ECSTATIC has the potential to decrease mortality and morbidity of these extremely ill infants and children.