ECMO Hemostatic Transfusions in Children

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 ECSTATIC pilot, a randomized controlled 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 (9 in the US and 1 in Israel). The investigators will enroll an anticipated 50 consecutive critically ill children (0 to <18 years of age), admitted to a participating pediatric, neonatal, or cardiac intensive care unit (PICU/NICU/CICU), on ECMO, and who have either no bleeding or minimal bleeding.

Non-bleeding children 0 to less than 18 years of age will be randomized 1:1 to either a platelet transfusion threshold of 90 x10e9/L (higher platelet transfusion strategy) or 50 x10e9/L (lower platelet transfusion strategy). Participants will be followed until progression to severe bleeding and/or severe thrombosis, decannulation from ECMO, or reach 21 days.

In this pilot, the investigators will test the separation between the lower and higher transfusion strategies. The primary outcomes will be the separation between pre-transfusion platelet counts, and the total platelet dose (in mL/kg/run). Secondary outcomes will be feasibility of patient enrollment and ability for an adjudication committee to determine the severity of bleeding and thrombotic outcomes.

The purpose of this pilot study is to determine the feasibility of the transfusion strategies, intervention parameters, subject availability, and other information regarding outcomes that are essential to complete the design of a large randomized controlled trial.

The large future trial will evaluate the efficacy of the two transfusion strategies, in terms of progression to severe bleeding and/or severe thrombosis. To adequately calculate the sample size, the investigators need to know the difference between the pre-transfusion platelet counts, the screening and inclusion rates, the proportion of patients who are consented within the first 24 hours after cannulation, the proportion of transfusions that are compliant with each arm's strategy, and the number of temporary suspensions.

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 pilot trial will provide necessary and sufficient information to proceed with the definitive ECSTATIC Randomized Controlled Trial (RCT) to evaluate the impact of a lower prophylactic platelet transfusion threshold on the clinical outcomes in children on ECMO. ECSTATIC has the potential to optimize efficacy, to reduce platelet transfusion exposure and to decrease mortality and morbidity of these extremely ill infants and children.

• Platelet Transfusion (Biological): Participants will be transfused according to the assigned threshold for each group, with a transfusion dose of 10 mL/kg, up to one adult unit.

Primary outcomes

• Total Platelet Transfusion Dose [up to day 21]: The total dose (in mL/kg/day) will be computed by the research team, by dividing the total platelet transfusion volume by the patient's weight at admission and the number of days of intervention.
• Pre-transfusion Platelet Count [During intervention]: Pre-transfusion platelet count, during intervention

Secondary outcomes

• Feasibility Assessed by the Screening Rate [At screening]: Feasibility will be assessed by the number of eligible participants that were screened.
• Feasibility Assessed by the Inclusion Rate [At screening]: Feasibility will be assessed by the number of eligible participants that were enrolled.
• Feasibility Assessed by the Number of Informed Consents Signed in the First 24 Hours Post Cannulation. [At screening]: Feasibility will be assessed by the number of participants that sign consent within the first 24 hours after ECMO cannulation.
• Compliance With Transfusion Thresholds [up to Day 21]: The proportion of transfusions that were given for platelet counts below the arm threshold will be computed to assess compliance.
• Participants With at Least One Temporary Suspension [up to Day 21]: The number of participants who required at least one temporary suspension during ECMO.
• Duration for Temporary Suspensions [up to Day 21]: The investigators will collect information on the duration of each suspension.
• Progression to Composite Outcome of Severe Bleeding and/or Severe Thrombotic Event [up to Day 21]: The investigators will collect the proportion of participants who progress to a composite outcome of severe bleeding and/or severe thrombosis. The outcome will be adjudicated by an external review committee, blinded to the allocation arm.
• Number of Participants Who Were Withdrawn and/or Lost to Follow-up [Up to 90 days]: Number of patients who withdraw from the study and/or are lost to follow-up (i.e., withdraw and/or are missing 90-day mortality assessment)

Sex: All, ages: any to 18 Years

Inclusion Criteria:

* Critically ill children (0 to <18 years of age)
* Admitted to a participating pediatric, neonatal, or cardiac intensive care unite (PICU/NICU/CICU)
* On extracorporeal Membrane Oxygenation (ECMO)
* Who have either no bleeding or minimal bleeding, within 24 hours of cannulation. Minimal bleeding is defined as:

  * streaks of blood in endotracheal tube or during suctioning only
  * streaks of blood in nasogastric tube
  * macroscopic hematuria
  * subcutaneous bleeding (including hematoma and petechiae) < 5 cm in diameter
  * quantifiable bleeding < 1mL/kg/hr (e.g., chest tube)
  * bloody dressings required to be changed no more often than each 6hr, or weighing no more than 1mL/kg/hr if weighed, due to slow saturation

Exclusion Criteria:

* Post-conception age < 37 weeks at time of screening
* Underlying oncologic diagnosis (defined as receipt of chemotherapy or radiation in the last six months) or recipient of bone marrow transplant in the last year
* Congenital bleeding disorder
* Pregnant or admitted post-partum
* Decision to withdraw or withhold some critical care or interventions
* Known objection to blood transfusions
* On ECMO for > 24 hours at time of enrollment

Participant flow

Outcome results

• Total Platelet Transfusion Dose (Primary), Median, mL/kg/day: Higher Platelet Transfusion Strategy 7.4 (0 to 16.6); Lower Platelet Transfusion Strategy 0 (0 to 8.4)
• Feasibility Assessed by the Screening Rate (Secondary), Count of participants, Participants: All Screened Patients 123
• Feasibility Assessed by the Inclusion Rate (Secondary), Number, participants: Number of Eligible Patients 50
• Feasibility Assessed by the Number of Informed Consents Signed in the First 24 Hours Post Cannulation. (Secondary), Number, participants: Approached Patients 50
• Compliance With Transfusion Thresholds (Secondary), Number, Compliant transfusion: Higher Platelet Transfusion Strategy 316; Lower Platelet Transfusion Strategy 386
• Participants With at Least One Temporary Suspension (Secondary), Count of participants, Participants: Higher Platelet Transfusion Strategy 6; Lower Platelet Transfusion Strategy 8
• Duration for Temporary Suspensions (Secondary), Median, Hours: Higher Platelet Transfusion Strategy 7.5 (1.5 to 19.6); Lower Platelet Transfusion Strategy 13.5 (1.8 to 23.7)
• Progression to Composite Outcome of Severe Bleeding and/or Severe Thrombotic Event (Secondary), Count of participants, Participants: Higher Platelet Transfusion Strategy 4; Lower Platelet Transfusion Strategy 5
• Number of Participants Who Were Withdrawn and/or Lost to Follow-up (Secondary), Count of participants, Participants: Higher Platelet Transfusion Strategy 2; Lower Platelet Transfusion Strategy 2
• Pre-transfusion Platelet Count (Primary), Median, 10^9 cells/L: Higher Platelet Transfusion Strategy 79 (70 to 86); Lower Platelet Transfusion Strategy 43 (39 to 47)

Adverse events

Time frame: From randomization up to 24 hours after the end of the intervention, up to 90 days

Serious adverse events by term

Other adverse events by term

Limitations and caveats: No limitations or caveats to report.

• Results publication: Nellis ME, Barney BJ, Coles G, Cholette JM, Choudhury TA, Furlong-Dillard J, Ozment C, Bain J, Niebler RA, Chegondi M, Badheka A, Schiller O, Shostak E, Joashi U, Paden M, Alvey JS, Muszynski JA, Spinella PC, Tucci M, Lacroix J, Stanworth S, O'Neil ER, Pollak U, Bahr T, Kumar SR, Karam O; BloodNet and PediECMO; subgroups of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI). Platelet Transfusion Thresholds for Children Supported by Extracorporeal Membrane Oxygenation: The Extracorporeal Membrane Oxygenation Hemostatic Transfusions in Children (ECSTATIC) Feasibility Clinical Trial. Crit Care Med. 2026 Mar 1;54(3):410-421. doi: 10.1097/CCM.0000000000006995. Epub 2025 Dec 23. PMID 41432485

• Study Protocol and Statistical Analysis Plan (PDF, 2024-05-15)

• Oliver Karam, MD, PhD, Principal investigator, Yale University
• Marianne Nellis, MD, MS, Principal investigator, NewYork-Presbyterian / Weill Cornell

NIH grants: R34HL159119