Marie E. Steiner

BACKGROUND: Blood transfusion and hemorrhage control procedures can be unreliable surrogates for bleeding requiring intervention in children. Some receive unnecessary blood transfusions or lack intraoperative findings for hemorrhage, while others die before an intervention occurs. Standardized criteria for adjudicating the presence of actionable hemorrhage are needed. We aimed to define expert consensus criteria for retrospectively identifying actionable hemorrhage within 6 hours of emergency department (ED) arrival. METHODS: Experts from six specialties involved in pediatric trauma care participated in a modified Delphi study. Panelists were prompted to consider “actionable hemorrhage” as “severe bleeding or injuries at risk of progression to class III or IV shock without prompt intervention.” In Round 1, panelists answered five free-response questions identifying criteria for actionable hemorrhage, including indicators for transfusion and hemorrhage control procedures, postmortem findings, and other relevant factors. Responses were consolidated and rated on a five-point strength-of-indication scale in subsequent rounds. Consensus was defined a priori as ≥70% agreement among panelists. Stability of consensus ( p >0.05) between rounds was assessed using the Wilcoxon Signed-Rank Test. RESULTS: Three Delphi rounds were required to achieve a stable consensus. Twenty-nine of 32 participating panelists participated in all three rounds. Thirteen statements achieved stable consensus as strong indicators of actionable hemorrhage. Criteria with the highest agreement included partial/total resection of intrathoracic/abdominal bleeding solid organs (96.4%), hemoglobinJ Trauma Acute Care Surg . 2026;00:00-00. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.) LEVEL OF EVIDENCE: Diagnostic Test/Criteria; Level III.

Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection characterized by multiorgan involvement and inflammation. Testing of cellular function ex vivo to understand the aberrant immune response in MIS-C is limited. Despite strong Ab production in MIS-C, SARS-CoV-2 nucleic acid testing can remain positive for 4–6 wk postinfection. Therefore, we hypothesized that dysfunctional cell-mediated Ab responses downstream of Ab production may be responsible for delayed clearance of viral products in MIS-C. In MIS-C, monocytes were hyperfunctional for phagocytosis and cytokine production, whereas NK cells were hypofunctional for both killing and cytokine production. The decreased NK cell cytotoxicity correlated with an NK exhaustion marker signature and systemic IL-6 levels. Potentially providing a therapeutic option, cellular engagers of CD16 and SARS-CoV-2 proteins were found to rescue NK cell function in vitro. Taken together, our results reveal dysregulation in Ab-mediated cellular responses of myeloid and NK cells that likely contribute to the immune pathology of this disease.

Background: Low titer group O whole blood (LTOWB) is commonly used for severe bleeding in trauma patients. LTOWB may also benefit young children requiring cardiac surgery with cardiopulmonary bypass (CPB) at risk of severe bleeding.Study Design and Methods: In this retrospective study, children p = .28). Median (IQR) DT output was 22 (15–32) in CT versus 22 (16–28) in LTOWB+CT groups, (p = .27). There were no differences in death, renal failure and a composite of death and renal failure between the two groups, but there were statistically fewer re‐explorations for bleeding in the LTOWB+CT group (p < .001).Conclusions: The use of LTOWB appears to be safe in <2 years old undergoing cardiac surgery and may reduce re‐explorations for severe bleeding. Large trials are needed to determine the efficacy and safety of LTOWB in this population with severe bleeding.

OBJECTIVES: To identify and prioritize research questions for anticoagulation and hemostasis management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus. DATA SOURCES: Systematic review was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial consensus conferences of international, interprofessional experts in the management of ECMO for critically ill neonates and children. STUDY SELECTION: The management of ECMO anticoagulation for critically ill neonates and children. DATA EXTRACTION: Within each of the eight subgroups, two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. DATA SYNTHESIS: Following the systematic review of MEDLINE, EMBASE, and Cochrane Library databases from January 1988 to May 2021, and the consensus process for clinical recommendations and consensus statements, PEACE panel experts constructed research priorities using the Child Health and Nutrition Research Initiative methodology. Twenty research topics were prioritized, falling within five domains (definitions and outcomes, therapeutics, anticoagulant monitoring, protocolized management, and impact of the ECMO circuit and its components on hemostasis). CONCLUSIONS: We present the research priorities identified by the PEACE expert panel after a systematic review of existing evidence informing clinical care of neonates and children managed with ECMO. More research is required within the five identified domains to ultimately inform and improve the care of this vulnerable population.

Background: Extracorporeal cardiopulmonary resuscitation improves outcomes after out‐of‐hospital cardiac arrest. However, bleeding and thrombosis are common complications. We aimed to describe the incidence and predictors of bleeding and thrombosis and their association with in‐hospital mortality. Methods and Results: Consecutive patients presenting with refractory ventricular tachycardia/ventricular fibrillation out‐of‐hospital cardiac arrest between December 2015 and March 2022 who met the criteria for extracorporeal cardiopulmonary resuscitation initiation at our center were included. Major bleeding was defined by the Extracorporeal Life Support Organization's criteria. Adjusted analyses were done to seek out risk factors for bleeding and thrombosis and evaluate their association with mortality. Major bleeding occurred in 135 of 200 patients (67.5%), with traumatic bleeding from cardiopulmonary resuscitation in 73 (36.5%). Baseline demographics and arrest characteristics were similar between groups. In multivariable analysis, decreasing levels of fibrinogen were independently associated with bleeding (adjusted hazard ratio [aHR], 0.98 per every 10 mg/dL rise [95% CI, 0.96–0.99]). Patients who died had a higher rate of bleeds per day (0.21 versus 0.03, P <0.001) though bleeding was not significantly associated with in‐hospital death (aHR, 0.81 [95% CI. 0.55–1.19]). A thrombotic event occurred in 23.5% (47/200) of patients. Venous thromboembolism occurred in 11% (22/200) and arterial thrombi in 15.5% (31/200). Clinical characteristics were comparable between groups. In adjusted analyses, no risk factors for thrombosis were identified. Thrombosis was not associated with in‐hospital death (aHR, 0.65 [95% CI, 0.42–1.03]). Conclusions: Bleeding is a frequent complication of extracorporeal cardiopulmonary resuscitation that is associated with decreased fibrinogen levels on admission whereas thrombosis is less common. Neither bleeding nor thrombosis was significantly associated with in‐hospital mortality.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe complication of SARS-CoV-2 infection characterized by multi-organ involvement and inflammation. Testing of cellular function ex vivo to understand the aberrant immune response in MIS-C is limited. Despite strong antibody production in MIS-C, SARS-CoV-2 nucleic acid testing can remain positive for 4-6 weeks after infection. Therefore, we hypothesized that dysfunctional cell-mediated antibody responses downstream of antibody production may be responsible for delayed clearance of viral products in MIS-C. In MIS-C, monocytes were hyperfunctional for phagocytosis and cytokine production, while natural killer (NK) cells were hypofunctional for both killing and cytokine production. The decreased NK cell cytotoxicity correlated with an NK exhaustion marker signature and systemic IL-6 levels. Potentially providing a therapeutic option, cellular engagers of CD16 and SARS-CoV-2 proteins were found to rescue NK cell function in vitro. Together, our results reveal dysregulation in antibody-mediated cellular responses unique to MIS-C that likely contribute to the immune pathology of this disease. Summary MIS-C is a severe complication of SARS-CoV-2 infection characterized by multi-organ involvement and inflammation. Limited studies tested cellular function ex vivo to understand the aberrant immune response in MIS-C. We found dysregulation in antibody-mediated cellular responses unique to MIS-C that likely contribute to the immune pathology of this disease

Inherited and acquired coagulopathy are frequently associated with major bleeding in severe trauma, cardiac surgery with cardiopulmonary bypass, and postpartum hemorrhage. Perioperative management is multifactorial and includes preoperative optimization and discontinuation of anticoagulants and antiplatelet therapy in elective procedures. Prophylactic or therapeutic use of antifibrinolytic agents is strongly recommended in guidelines and has been shown to reduce bleeding and need for allogeneic blood administration. In the context of bleeding induced by anticoagulants and/or antiplatelet therapy, reversal strategies should be considered when available. Targeted goal-directed therapy using viscoelastic point-of-care monitoring is increasingly used to guide the administration of coagulation factors and allogenic blood products. In addition, damage control surgery, which includes tamponade of large wound areas, leaving surgical fields open, and other temporary maneuvers, should be considered when bleeding is refractory to hemostatic measures.