Patient-tailored platelet transfusion practices for children supported by extracorporeal membrane oxygenation.

BACKGROUND AND OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) serves as cardiopulmonary therapy in critically ill patients with respiratory/heart failure and often necessitates multiple blood product transfusions. The administration of platelet transfusions during ECMO is triggered by the presence or risk of significant bleeding. Most paediatric ECMO programmes follow guidelines that recommend a platelet transfusion threshold of 80-100 × 109/L. To reduce exposure to platelets, we developed a practice to dynamically lower the threshold to ~20 × 109/L. We describe our experience with patient-tailored platelet thresholds and related bleeding outcomes. MATERIALS AND METHODS: We retrospectively evaluated our platelet transfusion policy, bleeding complications and patient outcome in 229 ECMO-supported paediatric patients in our unit. RESULTS: We found that more than 97.4% of patients had a platelet count <100 × 109/L at some point during their ECMO course. Platelets were transfused only on 28.5% of ECMO days; and 19.2% of patients never required a platelet transfusion. The median lowest platelet count in children who had bleeding events was 25 × 109/L as compared to 33 × 109/L in children who did not bleed (p < 0.001). Our patients received fewer platelet transfusions and did not require more red blood cell transfusions, nor did they experience more haemorrhagic complications. CONCLUSION: We have shown that a restrictive, 'patient-tailored' rather than 'goal-directed' platelet transfusion policy is feasible and safe, which can greatly reduce the use of platelet products. Although there was a difference in the lowest platelet counts in children who bled versus those who did not, the median counts were much lower than current recommendations.

Epidemiology of anticoagulation for children supported by extracorporeal membrane oxygenation in the United States: A Pediatric Hospital Information System database study.

INTRODUCTION: Due to the risk of thrombosis, nearly all children supported by extracorporeal membrane oxygenation (ECMO) receive systemic anticoagulation. While heparin has traditionally been used, there are reports of increased use of direct thrombin inhibitors. We sought to describe the use of anticoagulation in children supported by ECMO in the United States using a large administrative database. METHODS: We performed a retrospective cohort study of children supported by ECMO within the Pediatric Health Information System (PHIS) database. Pediatric encounters involving ECMO from 2012 to 2020 were identified. Data regarding demographics, diagnoses, anticoagulation, complications, and outcomes were extracted for eligible encounters. RESULTS: Eleven thousand five hundred ninety-five encounters that involved ECMO were identified. Fifty-four percent were male with an age range of 0-17 years and a median (IQR) age of 0 (0-2) years. Unfractionated heparin (UFH) only was used in 94% (95% CI: 93.6-94.5%) of encounters and UFH followed by bivalirudin in 5% (95% CI: 4.3-5.1%) of cases. There was a significant difference in the use of bivalirudin from 2012 to 2020 (p < 0.001). Differences in anticoagulation regimens were observed between infants and children (p = 0.004) and between those with and without cardiac indications for ECMO (p < 0.001). Four percent (95% CI: 4.1-4.8%) of encounters were associated with diagnostic coding for thrombosis and differences in occurrence of thrombosis were observed between different anticoagulant regimens (p < 0.001). CONCLUSIONS: Though the majority of children on ECMO in the United States receive heparin anticoagulation, there is an increase in use of direct thrombin inhibitors. Prospective studies must evaluate the efficacy of different anticoagulants in this patient population.

Evaluating Airway Management in Patients With Trisomy 21 in the PICU and Cardiac ICU: A Retrospective Cohort Study.

OBJECTIVES: Children with trisomy 21 often have anatomic and physiologic features that may complicate tracheal intubation (TI). TI in critically ill children with trisomy 21 is not well described. We hypothesize that in children with trisomy 21, TI is associated with greater odds of adverse airway outcomes (AAOs), including TI-associated events (TIAEs), and peri-intubation hypoxemia (defined as > 20% decrease in pulse oximetry saturation [Sp o2 ]). DESIGN: Retrospective database study using the National Emergency Airway Registry for Children (NEAR4KIDS). SETTING: Registry data from 16 North American PICUs and cardiac ICUs (CICUs), from January 2014 to December 2020. PATIENTS: A cohort of children under 18 years old who underwent TI in the PICU or CICU from in a NEAR4KIDS center. We identified patients with trisomy 21 and selected matched cohorts within the registry. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 8401 TIs in the registry dataset. Children with trisomy 21 accounted for 274 (3.3%) TIs. Among those with trisomy 21, 84% had congenital heart disease and 4% had atlantoaxial instability. Cervical spine protection was used in 6%. The diagnosis of trisomy 21 (vs. without) was associated with lower median weight 7.8 (interquartile range [IQR] 4.5-14.7) kg versus 10.6 (IQR 5.2-25) kg ( p < 0.001), and more higher percentage undergoing TI for oxygenation (46% vs. 32%, p < 0.001) and ventilation failure (41% vs. 35%, p = 0.04). Trisomy 21 patients had more difficult airway features (35% vs. 25%, p = 0.001), including upper airway obstruction (14% vs. 8%, p = 0.001). In addition, a greater percentage of trisomy 21 patients received atropine (34% vs. 26%, p = 0.004); and, lower percentage were intubated with video laryngoscopy (30% vs. 37%, p = 0.023). After 1:10 (trisomy 21:controls) propensity-score matching, we failed to identify an association difference in AAO rates (absolute risk difference -0.6% [95% CI -6.1 to 4.9], p = 0.822). CONCLUSIONS: Despite differences in airway risks and TI approaches, we have not identified an association between the diagnosis of trisomy 21 and higher AAOs.

Scenario Decision-Making About Plasma and Platelet Transfusion for Intracranial Monitor Placement: Cross-Sectional Survey of Pediatric Intensivists and Neurosurgeons.

OBJECTIVES: To report pediatric intensivists' and pediatric neurosurgeons' responses to case-based scenarios about plasma and platelet transfusions before intracranial pressure (ICP) monitor placement in children with severe traumatic brain injury (TBI). DESIGN: Cross-sectional, electronic survey to evaluate reported plasma and platelet transfusion decisions in eight scenarios of TBI in which ICP monitor placement was indicated. SETTING: Survey administered through the Pediatric Acute Lung Injury and Sepsis Investigators and the American Association of Neurologic Surgeons. SUBJECTS: Pediatric intensivists and pediatric neurosurgeons. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 184 participants responded (85 identified as pediatric intensivists and 54 as pediatric neurosurgeons). In all eight scenarios, the majority of respondents reported that they would base their decision-making about plasma transfusion on international normalized ratio (INR) alone (60-69%), or platelet transfusion on platelet count alone (83-86%). Pediatric intensivists, as opposed to pediatric neurosurgeons, more frequently reported that they would have used viscoelastic testing in their consideration of plasma transfusion (32% vs. 7%, p < 0.001), as well as to guide platelet transfusions (29 vs. 8%, p < 0.001), for the case-based scenarios. For all relevant case-based scenarios, pediatric neurosurgeons in comparison with pediatric reported that they would use a lower median (interquartile range [IQR]) INR threshold for plasma transfusion (1.5 [IQR 1.4-1.7] vs. 2.0 [IQR 1.5-2.0], p < 0.001). Overall, in all respondents, the reported median platelet count threshold for platelet transfusion in the case-based scenario was 100 (IQR 50-100) ×10 9 /L, with no difference between specialties. CONCLUSIONS: Despite little evidence showing efficacy, when we tested specialists' decision-making, we found that they reported using INR and platelet count in pediatric case-based scenarios of TBI undergoing ICP monitor placement. We also found that pediatric intensivists and pediatric neurosurgeons had differences in decision-making about the scenarios.

Bleeding in Critically Ill Children With Malignancy or Hematopoietic Cell Transplant: A Single-Center Prospective Cohort Study.

OBJECTIVES: To determine the incidence of bleeding in critically ill children with malignancy and to describe associated patient characteristics, interventions, and clinical outcomes. DESIGN: Prospective cohort study. SETTING: PICU in a specialized cancer hospital. PATIENTS: Children with malignancy or hematopoietic cell transplant 0-18 years of age were admitted to the PICU from November 2020 to November 2021. INTERVENTIONS: None. MEASUREMENTS: Patient demographic data, laboratory values, and PICU outcome data were collected. Bleeding was classified according to the Bleeding Assessment Scale in Critically Ill Children. MAIN RESULTS: Ninety-three bleeding patients were enrolled, and a total of 322 bleeding days were recorded. The median (interquartile range [IQR]) age was 5.8 (2.9-11.8) years and 56% (52/93) of the patients were male. There were 121 new bleeding episodes, in 593 at-risk person-days, translating into a 20% incidence rate per day (95% CI, 17-24%). The incidence of severe, moderate, and minimal bleeding was 2% (95% CI, 1-3), 4% (95% CI, 3-6), and 14% (95% CI, 12-17), respectively. Of the new bleeding episodes, 9% were severe, 25% were moderate and 66% were minimal. Thrombocytopenia was the only laboratory value independently associated with severe bleeding ( p = 0.009), as compared to minimal and moderate bleeding episodes. History of radiation therapy was independently associated with severe bleeding ( p = 0.04). We failed to identify an association between a history of stem cell transplant ( p = 0.49) or tumor type ( p = 0.76), and bleeding severity. Patients were transfused any blood product on 28% (95% CI, 22-34) of the bleeding days. Severe bleeding was associated with increased length of mechanical ventilation ( p = 0.003), longer PICU stays ( p = 0.03), and higher PICU mortality ( p = 0.004). CONCLUSIONS: In this prospective cohort of children with malignancy, the incidence rate of bleeding was 20%. Most events were classified as minimal bleeding. Low platelet count and radiation therapy were variables independently associated with severe bleeding episodes.

Prophylactic Platelet Transfusion: Is There Evidence of Benefit, Harm, or No Effect?

The optimal use of prophylactic platelet transfusion remains uncertain in a number of clinical scenarios. Platelet count thresholds have been established in patients with hematologic malignancies, yet thresholds backed by scientific data are limited or do not exist for many patient populations. Clinical scenarios involving transfusion thresholds for thrombocytopenic patients with critical illness, need for surgery or invasive procedures, or those involving specials populations like children and neonates, lack clear evidence for discerning favorable outcomes without undue risk related to platelet transfusion. In addition, while prophylactic platelet transfusions are administered with the goal of enhancing hemostasis, increasing evidence supports critical nonhemostatic roles for platelets related to innate and adaptive immunity, inflammation, and angiogenesis, which may impact patient responses and outcomes. Here we review several recent studies conducted in adult or pediatric patients that highlight the limitations in our current understanding of prophylactic platelet transfusion. Together, these studies underscore the need for additional research, especially in the form of robust randomized clinical trials and integrating additional parameters beyond the platelet count. Future research at the basic, translational, and clinical levels will best define the optimal role for prophylactic transfusion across the lifespan and its broader impact on health and disease.

Association between Platelet Transfusion and Delirium in Critically Ill Children.

Delirium is a frequent, serious, and preventable complication in critically ill children. Inflammation has been implicated as a mechanism for the development of delirium. Platelet transfusions may potentiate the body's pro-inflammatory responses. We hypothesized that receipt of platelets would be associated with delirium development in a pediatric intensive care unit (PICU). We performed a single-center retrospective cohort analysis including children admitted to the PICU between 2014 and 2018 who were transfused platelets within the first 14 days of admission. Data obtained included severity of illness, level of respiratory support, exposure to medications and blood products, as well as daily cognitive status. To account for time-dependent confounding, a marginal structural model (MSM) was constructed to delineate the relationship between platelet transfusion and next-day delirium. MSM demonstrated a 75% increase in the development of next-day delirium after transfusion of platelets (aOR 1.75, 95% CI 1.03-2.97). For every 1 cc/kg of platelet transfused, odds of next-day delirium increased by 9% (odds ratio 1.09, 95% CI 1.03-1.51). We reported an independent association between platelet transfusion and next-day delirium/coma after accounting for time-dependent confounders, with a dose-response effect. Minimizing platelet transfusions as much as clinically feasible may decrease delirium risk in critically ill children.

Pediatric firearm injury related emergency department visits and hospitalizations: a population-based study in the United States.

Background: Firearm injury (FI) is the leading cause of death in children and adolescents in the United States (US). We describe the epidemiology of pediatric FI-associated emergency department (ED) visits and hospitalizations in the US stratified by race and ethnicity. Methods: Data on pediatric (0-17-year-olds) FI were analyzed using the 2019 Nationwide Emergency Department Sample (NEDS) and Kids' Inpatient Database (KID), the largest all-payer databases in the US for ED visits and pediatric hospitalizations, respectively. FI encounters were stratified by race and ethnicity. Poisson regression was used to identify factors associated with in-hospital mortality. Sampling weights were applied to generate nationally representative estimates. Findings: There were 7017 pediatric ED visits with FI (NEDS); 85.0% (5961/7017) were male and 73.0% (5125/7017) were adolescents (15-17 years). Overall, 5.5% (384/7017) died in the ED; 53.1% (3727/7017) of ED encounters did not result in hospitalization. There were 2817 pediatric FI hospitalizations (KID); 84.1% (2369/2817) were male and 71.6% (2018/2817) were adolescents; 51.4% (1447/2817) of FI were unintentional, 42.8% (1207/2817) were assault-related, and 5.8% (163/2817) were self-inflicted. Black children had the highest proportion (52.6%; 1481/2817) of hospitalizations among all race and ethnicities (p < 0.0001 vs. White). White children had the highest proportion of hospitalizations for self-inflicted injuries (16.6% [91/551] vs. 4.9% [25/504; p < 0.0001] in Hispanics and 1.7% [24/1481] in Blacks; p < 0.0001). The majority (56.5%; 1591/2817) of hospitalizations were patients from low-income zip codes (median annual-household-income <$44,000); 70% (1971/2817) had Medicaid as the primary insurance payer. Overall, 8.0% (225/2817) died during FI-associated hospitalizations. Self-inflicted injuries had the highest in-hospital mortality (prevalence ratio = 8.20, 95% CI = 6.06-11.10 vs. unintentional). Interpretation: Black children and children with lower household incomes were disproportionately impacted by FI resulting from assaults and accidents, while White children had the highest proportion of self-inflicted FI injuries. Public health and legal policy interventions are needed to prevent pediatric FI. Funding: US National Institutes of Health.

Epidemiology of Platelet Transfusions in Hospitalized Children: A Pediatric Hospital Information System Database Study.

OBJECTIVES: To describe the epidemiology and complications of platelet transfusions among hospitalized pediatric patients during 2010 to 2019. METHODS: We performed a retrospective cohort study of hospitalized children within the Pediatric Health Information System database. Pediatric encounters receiving at least one platelet transfusion during hospitalization from 2010 to 2019 were identified. Data regarding demographics, diagnoses, procedures required during hospitalization, complications, and outcomes were extracted for eligible encounters. RESULTS: Within the Pediatric Health Information System database, 6 284 264 hospitalizations occurred from 2010 to 2019. A total of 244 464 hospitalizations required at least one platelet transfusion, yielding a prevalence of 3.89% (95% confidence interval [CI], 3.87%-3.91%). Transfusion prevalence did not change significantly across the decade (P value = .152). Two-thirds of children receiving platelet transfusions were in their first 6 years of life, and the majority identified as male (55%). Recipients most commonly had diseases of the circulatory system (21%, 52 008 of 244 979), perinatal disorders (16%, 38 054 of 244 979), or diseases of the hematologic/immune systems (15%, 37 466 of 244 979). When adjusted for age, support by extracorporeal membrane oxygenation, mechanical ventilation, surgical intervention, and diagnostic category, the odds of thrombosis, infection, and mortality increased by 2% (odds ratio [OR], 1.02; 95% CI, 1.016-1.020), 3% (OR, 1.03; 95% CI, 1.028-1.033), and 7% (OR, 1.07; 95% CI, 1.067-1.071), respectively, with each additional transfusion. CONCLUSIONS: The prevalence of platelet transfusions among pediatric inpatients remained consistent across the decade. Our finding that increasing numbers of transfusions may be associated with elevated morbidity and mortality is consistent with other observation and experimental studies, highlighting the need to be thoughtful in weighing risks and benefits when prescribing repeated platelet transfusions to hospitalized children.

Anticoagulation and hemostasis on extracorporeal membrane oxygenation.

PURPOSE OF REVIEW: The purpose of this review is to describe the hemostatic changes induced by extracorporeal membrane oxygenation (ECMO), the need to balance the risks of bleeding and clotting with anticoagulation and hemostatic transfusions, and the inherent risks to these interventions. RECENT FINDINGS: Both bleeding and clotting are frequent complications of ECMO. To prevent clotting events, virtually, all children are anticoagulated. However, the optimal anticoagulation strategy is unknown. A recent systematic review of observational studies showed that anti-Xa-guided strategies were associated with a two-fold decrease in bleeding and no increase in clotting complications. These results need to be tested in randomized controlled trials. To avoid bleeding events, platelet transfusions are frequently prescribed to children on ECMO. However, platelet transfusions have recently been shown to be independently associated with increased bleeding and clotting. Therefore, the optimal platelet transfusion strategy must be evaluated appropriately. SUMMARY: Most patients on ECMO will develop either a hemorrhagic or thrombotic complication. Balancing these risks involves careful titration of anticoagulation to prevent clotting and hemostatic transfusions to prevent bleeding. As the current level of evidence is low, prospective randomized trials are needed.

Epidemiology of severe bleeding in children following cardiac surgery involving cardiopulmonary bypass: use of Bleeding Assessment Scale for critically Ill Children (BASIC).

OBJECTIVES: To describe the epidemiology of severe bleeding in the immediate post-operative period in children who undergo cardiopulmonary bypass surgery using the Bleeding Assessment Scale for critically Ill Children (BASIC). STUDY DESIGN: Retrospective cohort study in a paediatric ICU from 2015 to 2020. RESULTS: 356 children were enrolled; 59% were male with median (IQR) age 2.1 (0.5-8) years. Fifty-seven patients (16%) had severe bleeding in the first 24 hours post-operatively. Severe bleeding was observed more frequently in younger and smaller children with longer bypass and cross-clamp times (p-values <0.001), in addition to higher surgical complexity (p = 0.048). Those with severe bleeding received significantly more red blood cells, platelets, plasma, and cryoprecipitate in the paediatric ICU following surgery (all p-values <0.001). No laboratory values obtained on paediatric ICU admission were able to predict severe post-operative bleeding. Those with severe bleeding had significantly less paediatric ICU-free days (p = 0.010) and mechanical ventilation-free days (p = 0.013) as compared to those without severe bleeding. CONCLUSIONS: Applying the BASIC definition to our cohort, severe bleeding occurred in 16% of children in the first day following cardiopulmonary bypass. Severe bleeding was associated with worse clinical outcomes. Standard laboratory assays do not predict bleeding warranting further study of available laboratory tests.

Prophylactic Use of Antifibrinolytics During Pediatric Cardiac Surgery With Cardiopulmonary Bypass on Postoperative Bleeding and Transfusion: A Systematic Review and Meta-Analysis.

OBJECTIVES: To determine the effect of intraoperative antifibrinolytics, including tranexamic acid (TXA), aminocaproic acid (EACA), or aprotinin, on bleeding in children undergoing cardiac surgery with cardiopulmonary bypass (CPB). DATA SOURCES: Relevant articles were systematically searched from Ovid MEDLINE, Ovid EMBASE, CINAHL, Cochrane Library, and Web of Science to November 15, 2021. STUDY SELECTION: Abstracts were screened, and full texts were reviewed using predetermined inclusion and exclusion criteria using the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. DATA EXTRACTION: A standardized data extraction tool was used. DATA SYNTHESIS: Sixty-eight studies including 28,735 patients were analyzed. TXA compared with placebo resulted in a mean decrease in chest tube output of 9.1 mL/kg (95% CI, 6.0-12.3 mL/kg), I2 equals to 65.2%, p value of less than 0.001, platelet requirement of 2.9 mL/kg (95% CI, 0.1-5.8 mL/kg), I2 =72.5%, p value less than 0.001 and plasma requirement of 4.0 mL/kg (95% CI, 0.6-7.2 mL/kg), I2 equals to 94.5%, p value less than0.001. Aprotinin compared with placebo resulted in a mean decrease in chest tube output of 4.3 mL/kg (2.4-6.2 mL/kg), I2 equals to 66.3%, p value of less than 0.001, platelet transfusion of 4.6 mL/kg (95% CI, 0.6-8.6 mL/kg), I2 equals to 93.6%, p value of less than 0.001, and plasma transfusion of 7.7 mL/kg (95% CI, 2.1-13.2 mL/kg), I2 equals to 95.3%, p value of less than 0.001. EACA compared with placebo resulted in a mean decrease in chest tube output of 9.2 mL/kg (2.3-21.0 mL/kg), I2 equals to 96.4%, p value of less than 0.001, RBC transfusion of 7.2 mL/kg (95% CI, 2.4-12.1 mL/kg), I2 equals to 94.5%, p value equals to 0.002, and platelet transfusion of 10.7 mL/kg (95% CI, 2.9-18.5 mL/kg), I2 equals to 0%, p value of less than 0.001. No statistical difference was observed in chest tube output when TXA was compared with aprotinin. Subgroup analysis of cyanotic patients showed a significant decrease in chest tube output, platelet requirement, and plasma requirement for patients receiving aprotinin. Overall, the quality of evidence was moderate. CONCLUSIONS: Antifibrinolytics are effective at decreasing blood loss and blood product requirement in children undergoing cardiac surgery with CPB although the quality of evidence is only moderate.

Pediatric platelet transfusions in critical illness: a narrative review of recent studies.

PURPOSE OF REVIEW: We sought to describe the current use of platelet transfusions, harms associated with platelet transfusion, new methods of platelet processing that attempt to address these harms, and recent platelet transfusion guidance specific to critically ill children. RECENT FINDINGS: Platelet transfusions have been associated with significant morbidity and mortality. New processing techniques, such as pathogen reduction, have been developed to combat infectious risks but in a recent trial of platelet transfusion thresholds in neonates, transfusing platelets more liberally was associated with increased bleeding and mortality. SUMMARY: Recent efforts to develop evidence-based guidelines for platelet transfusion in critically ill children were limited by the lack of evidence. However, given the significant risks, restrictive transfusion thresholds should be considered.

Transfusion-Associated Delirium in Children: No Difference Between Short Storage Versus Standard Issue RBCs.

OBJECTIVES: Primary objective is to determine if transfusion of short storage RBCs compared with standard issue RBCs reduced risk of delirium/coma in critically ill children. Secondary objective is to assess if RBC transfusion was independently associated with delirium/coma. DESIGN: This study was performed in two stages. First, we compared patients receiving either short storage or standard RBCs in a multi-institutional prospective randomized controlled trial. Then, we compared all transfused patients in the randomized controlled trial with a single-center cohort of nontransfused patients matched for confounders of delirium/coma. SETTING: Twenty academic PICUs who participated in the Age of Transfused Blood in Critically Ill Children trial. PATIENTS: Children 3 days to 16 years old who were transfused RBCs within the first 7 days of admission. INTERVENTIONS: Subjects were randomized to either short storage RBC study arm (defined as RBCs stored for up to seven days) or standard issue RBC study arm. In addition, subjects were screened for delirium prior to transfusion and every 12 hours after transfusion for up to 3 days. MEASUREMENTS AND MAIN RESULTS: Primary outcome measure was development of delirium/coma within 3 days of initial transfusion. Additional outcome measures were dose-response relationship between volume of RBCs transfused and delirium/coma, and comparison of delirium/coma rates between transfused patients and individually matched nontransfused patients. We included 146 subjects in the stage I analysis; 69 were randomized to short storage RBCs and 77 to standard issue. There was no significant difference in delirium/coma development between study arms (79.5% vs 70.1%; p = 0.184). In the stage II analysis, adjusted odds for delirium in the transfused cohort was more than eight-fold higher than in the nontransfused matched cohort, even after controlling for hemoglobin (adjusted odds ratio, 8.9; CI, 2.8-28.4; p < 0.001). CONCLUSIONS: RBC transfusions (and not anemia) are independently associated with increased odds of subsequent delirium/coma. However, storage age of RBCs does not affect delirium risk.

What Laboratory Tests and Physiologic Triggers Should Guide the Decision to Administer a Platelet or Plasma Transfusion in Critically Ill Children and What Product Attributes Are Optimal to Guide Specific Product Selection? From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding.

OBJECTIVES: To present consensus statements and supporting literature for plasma and platelet product variables and related laboratory testing for transfusions in general critically ill children from the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding. DESIGN: Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children. SETTING: Not applicable. PATIENTS: Critically ill pediatric patients at risk of bleeding and receiving plasma and/or platelet transfusions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A panel of 10 experts developed evidence-based and, when evidence was insufficient, expert-based statements for laboratory testing and blood product attributes for platelet and plasma transfusions. These statements were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative - Control/Avoidance of Bleeding experts. A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020. Consensus was obtained using the Research and Development/University of California, Los Angeles Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed five expert consensus statements and two recommendations in answer to two questions: what laboratory tests and physiologic triggers should guide the decision to administer a platelet or plasma transfusion in critically ill children; and what product attributes are optimal to guide specific product selection? CONCLUSIONS: The Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding program provides some guidance and expert consensus for the laboratory and blood product attributes used for decision-making for plasma and platelet transfusions in critically ill pediatric patients.

Plasma and Platelet Transfusion Strategies in Critically Ill Children Following Severe Trauma, Traumatic Brain Injury, and/or Intracranial Hemorrhage: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding.

OBJECTIVES: To present consensus statements and supporting literature for plasma and platelet transfusions in critically ill children with severe trauma, traumatic brain injury, and/or intracranial hemorrhage from the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding. DESIGN: Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children. SETTING: Not applicable. PATIENTS: Critically ill neonates and children with severe trauma, traumatic brain injury, and/or intracranial hemorrhage. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A panel of eight experts developed expert-based statements for plasma and platelet transfusions in critically ill neonates and children with severe trauma, traumatic brain injury, and/or intracranial hemorrhage. These statements were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding experts. A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020. Consensus was obtained using the Research and Development/University of California, Los Angeles Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed one good practice statement and six expert consensus statements. CONCLUSIONS: The lack of evidence precludes proposing recommendations on monitoring of the coagulation system and on plasma and platelets transfusion in critically ill pediatric patients with severe trauma, severe traumatic brain injury, or nontraumatic intracranial hemorrhage.

Plasma and Platelet Transfusions Strategies in Neonates and Children Undergoing Cardiac Surgery With Cardiopulmonary Bypass or Neonates and Children Supported by Extracorporeal Membrane Oxygenation: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding.

OBJECTIVES: To present the recommendations and consensus statements with supporting literature for plasma and platelet transfusions in critically ill neonates and children undergoing cardiac surgery with cardiopulmonary bypass or supported by extracorporeal membrane oxygenation from the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding. DESIGN: Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children. SETTING: Not applicable. PATIENTS: Critically ill neonates and children following cardiopulmonary bypass or supported by extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A panel of nine experts developed evidence-based and, when evidence was insufficient, expert-based statements for plasma and platelet transfusions in critically ill neonates and children following cardiopulmonary bypass or supported by extracorporeal membrane oxygenation. These statements were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding experts. A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020. Consensus was obtained using the Research and Development/University of California, Los Angeles Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed one good practice statement, two recommendations, and three expert consensus statements. CONCLUSIONS: Whereas viscoelastic testing and transfusion algorithms may be considered, in general, evidence informing indications for plasma and platelet transfusions in neonatal and pediatric patients undergoing cardiac surgery with cardiopulmonary bypass or those requiring extracorporeal membrane oxygenation support is lacking.

Plasma and Platelet Transfusion Strategies in Critically Ill Children Following Noncardiac Surgery and Critically Ill Children Undergoing Invasive Procedures Outside the Operating Room: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding.

OBJECTIVES: To present consensus statements and supporting literature for plasma and platelet transfusions in critically ill children following noncardiac surgery and critically ill children undergoing invasive procedures outside the operating room from the Transfusion and Anemia EXpertise Initiative - Control/Avoidance of Bleeding. DESIGN: Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children. SETTING: Not applicable. PATIENTS: Critically ill children undergoing invasive procedures outside of the operating room or noncardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A panel of 10 experts developed evidence-based and, when evidence was insufficient, expert-based statements for plasma and platelet transfusions in critically ill children following noncardiac surgery or undergoing invasive procedures outside of the operating room. These statements were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding experts. A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020. Consensus was obtained using the Research and Development/University of California, Los Angeles Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed eight expert consensus statements focused on the critically ill child following noncardiac surgery and 10 expert consensus statements on the critically ill child undergoing invasive procedures outside the operating room. CONCLUSIONS: Evidence regarding plasma and platelet transfusion in critically ill children in this area is very limited. The Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding Consensus Conference developed 18 pediatric specific consensus statements regarding plasma and platelet transfusion management in these critically ill pediatric populations.

Plasma and Platelet Transfusion Strategies in Critically Ill Children With Malignancy, Acute Liver Failure and/or Liver Transplantation, or Sepsis: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding.

OBJECTIVES: To present the consensus statements with supporting literature for plasma and platelet transfusions in critically ill neonates and children with malignancy, acute liver disease and/or following liver transplantation, and sepsis and/or disseminated intravascular coagulation from the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding. DESIGN: Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children. SETTING: Not applicable. PATIENTS: Critically ill neonates and children with malignancy, acute liver disease and/or following liver transplantation, and sepsis and/or disseminated intravascular coagulation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A panel of 13 experts developed evidence-based and, when evidence was insufficient, expert-based statements for plasma and platelet transfusions in critically ill neonates and children with malignancy, acute liver disease and/or following liver transplantation, and sepsis and/or disseminated intravascular coagulation. These statements were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding experts. A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020. Consensus was obtained using the Research and Development/University of California, Los Angeles Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed 12 expert consensus statements. CONCLUSIONS: In the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding program, the current absence of evidence for use of plasma and/or platelet transfusion in critically ill children with malignancy, acute liver disease and/or following liver transplantation, and sepsis means that only expert consensus statements are possible for these areas of practice.

Research Priorities for Plasma and Platelet Transfusion Strategies in Critically Ill Children: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding.

OBJECTIVES: To present a list of high-priority research initiatives for the study of plasma and platelet transfusions in critically ill children from the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding. DESIGN: Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children. SETTING: Not applicable. PATIENTS: Critically ill pediatric patients at risk of bleeding and receiving plasma and/or platelet transfusions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A panel of 13 experts developed research priorities for the study of plasma and platelet transfusions in critically ill children which were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding experts. The specific priorities focused on the following subpopulations: severe trauma, traumatic brain injury, intracranial hemorrhage, cardiopulmonary bypass surgery, extracorporeal membrane oxygenation, oncologic diagnosis or stem cell transplantation, acute liver failure and/or liver transplantation, noncardiac surgery, invasive procedures outside of the operating room, and sepsis and/or disseminated intravascular coagulation. In addition, tests to guide plasma and platelet transfusion, as well as component selection and processing, were addressed. We developed four general overarching themes and 14 specific research priorities using modified Research and Development/University of California, Los Angeles methodology. CONCLUSIONS: Studies are needed to focus on the efficacy/harm, dosing, timing, and outcomes of critically ill children who receive plasma and/or platelet transfusions. The completion of these studies will facilitate the development of evidence-based recommendations.