Objectives: To date, there are no published guidelines to direct RBC transfusion decision-making specifically for critically ill children. We present the recommendations from the Pediatric Critical Care Transfusion and Anemia Expertise Initiative. Design: Consensus conference series of multidisciplinary, international experts in RBC transfusion management of critically ill children. Setting: Not applicable. Intervention: None. Subjects: Children with, or children at risk for, critical illness who receive or are at risk for receiving a RBC transfusion. Methods: A panel of 38 content and four methodology experts met over the course of 2 years to develop evidence-based, and when evidence lacking, expert consensus-based recommendations regarding decision-making for RBC transfusion management and research priorities for transfusion in critically ill children. The experts focused on nine specific populations of critically ill children: general, respiratory failure, nonhemorrhagic shock, nonlife-threatening bleeding or hemorrhagic shock, acute brain injury, acquired/congenital heart disease, sickle cell/oncology/transplant, extracorporeal membrane oxygenation/ventricular assist/renal replacement support, and alternative processing. Data to formulate evidence-based and expert consensus recommendations were selected based on searches of PubMed, EMBASE, and Cochrane Library from 1980 to May 2017. Agreement was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. Measurements and Results: The Transfusion and Anemia Expertise Initiative consensus conference developed and reached consensus on a total of 102 recommendations (57 clinical [20 evidence based, 37 expert consensus], 45 research recommendations). All final recommendations met agreement, defined a priori as greater than 80%. A decision tree to aid clinicians was created based on the clinical recommendations. Conclusions: The Transfusion and Anemia Expertise Initiative recommendations provide important clinical guidance and applicable tools to avoid unnecessary RBC transfusions. Research recommendations identify areas of focus for future investigation to improve outcomes and safety for RBC transfusion.

Objectives: To present the recommendations and supporting literature for RBC transfusions in critically ill children with nonhemor-rhagic shock developed by the Pediatric Critical Care Transfusion and Anemia Expertise Initiative. Design: Consensus conference series of international, multidis-ciplinary experts in RBC transfusion management of critically ill children. Methods: The panel of 38 experts developed evidence-based, and when evidence was lacking, expert-based clinical recommendations as well as research priorities for RBC transfusions in critically ill children. The nonhemorrhagic shock subgroup included five experts. Electronic searches were conducted using PubMed, EMBASE, and Cochrane Library databases jrom 1980 to May 2017. Agreement was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. Results: Transfusion and Anemia Expertise Initiative Consensus Conference experts developed and voted on a total of four clinical and four research recommendations focused on RBC transfusion in the critically ill child with nonhemorrhagic shock. All recommendations reached agreement (> 80%). Of the four clinical recommendations, three were based on consensus panel expertise, whereas one was based on weak pediatric evidence. In hemodynamically stabilized critically ill children with a diagnosis of severe sepsis or septic shock, we recommend not administering a RBC transfusion if the hemoglobin concentration is greater than or equal to 7 g/dL. Future studies are needed to determine optimum transfusion thresholds for critically ill children with non-hemorrhagic shock undergoing acute resuscitation. Conclusions: The Transfusion and Anemia Expertise Initiative Consensus Conference developed pediatric-specific clinical and research recommendations regarding RBC transfusion in the critically ill child with nonhemorrhagic shock. Although agreement among experts was strong, available pediatric evidence was scant - revealing significant gaps in the existing literature.

Efforts to create platelet-like structures for the augmentation of haemostasis have focused solely on recapitulating aspects of platelet adhesion; more complex platelet behaviours such as clot contraction are assumed to be inaccessible to synthetic systems. Here, we report the creation of fully synthetic platelet-like particles (PLPs) that augment clotting in vitro under physiological flow conditions and achieve wound-triggered haemostasis and decreased bleeding times in vivo in a traumatic injury model. PLPs were synthesized by combining highly deformable microgel particles with molecular-recognition motifs identified through directed evolution. In vitro and in silico analyses demonstrate that PLPs actively collapse fibrin networks, an emergent behaviour that mimics in vivo clot contraction. Mechanistically, clot collapse is intimately linked to the unique deformability and affinity of PLPs for fibrin fibres, as evidenced by dissipative particle dynamics simulations. Our findings should inform the future design of a broader class of dynamic, biosynthetic composite materials.

Background: Quantitative and qualitative differences in the hemostatic systems exist between neonates and adults, including the presence of "fetal" fibrinogen, a qualitatively dysfunctional form of fibrinogen that exists until 1 yr of age. The consequences of "fetal" fibrinogen on clot structure in neonates, particularly in the context of surgery-associated bleeding, have not been well characterized. Here, the authors examine the sequential changes in clotting components and resultant clot structure in a small sample of neonates undergoing cardiac surgery and cardiopulmonary bypass (CPB). Methods: Blood samples were collected from neonates (n = 10) before surgery, immediately after CPB, and after the transfusion of cryoprecipitate (i.e., adult fibrinogen component). Clots were formed from patient samples or purified neonatal and adult fibrinogen. Clot structure was analyzed using confocal microscopy. Results: Clots formed from plasma obtained after CPB and after transfusion were more porous than baseline clots. Analysis of clots formed from purified neonatal and adult fibrinogen demonstrated that at equivalent fibrinogen concentrations, neonatal clots lack three-dimensional structure, whereas adult clots were denser with significant three-dimensional structure. Clots formed from a combination of purified neonatal and adult fibrinogen were less homogenous than those formed from either purified adult or neonatal fibrinogen. Conclusions: The results of this study confirm that significant differences exist in clot structure between neonates and adults and that neonatal and adult fibrinogen may not integrate well. These findings suggest that differential treatment strategies for neonates should be pursued to reduce the demonstrated morbidity of blood product transfusion.