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1.
Trial-related blood sampling and red-blood-cell transfusions in preterm infants
Lewis, A. E., Kappel, S. S., Hussain, S., Sangild, P. T., Zachariassen, G., Aunsholt, L.
Acta paediatrica (Oslo, Norway : 1992). 2023
Abstract
AIM: To determine if trial-related blood sampling increases the risk of later red-blood-cell (RBC) transfusion in very preterm infants, we compared the volume of clinical- and trial-related blood samples, in a specific trial and correlated to subsequent RBC transfusion. METHODS For 193 very preterm infants, participating in the FortiColos trial (NCT03537365), trial-related blood volume drawn was in accordance to ethical considerations established by the European Commission. Medical records were reviewed to assess the number and cumulated volume (mL/kg) of blood samples (both clinical- and trial-related). Data were compared with need of RBC transfusions during the first 28days of life. RESULTS Mean (SD) gestational age and bith weight was 28 ± 1 weeks and 1168 ± 301 g. In total, 11% of total blood volume was drawn for sampling (8.1 ± 5.1 mL/kg) and trial-related sampling accounted for 1.6 ± 0.6 mL/kg. Trial-related blood sampling had no impact on RBC transfusion (p=0.9). CONCLUSION Clinical blood sampling in very preterm infants is associated with blood loss and subsequent need for RBC transfusions. In a specific trial requiring blood samples, we found no additional burden of trial-related blood sampling. The study suggest that trial-related sampling is safe if European criteria are followed.
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Assessment of Hemostatic Profile in Neonates with Intrauterine Growth Restriction: A Systematic Review of Literature
Karapati E, Sokou R, Iliodromiti Z, Tsaousi M, Sulaj A, Tsantes AG, Petropoulou C, Pouliakis A, Tsantes AE, Boutsikou T, et al
Seminars in thrombosis and hemostasis. 2023
Abstract
Intrauterine growth restriction (IUGR) affects nearly 10 to 15% of pregnancies and is responsible for many short- and long-term adverse consequences, including hemostatic derangement. Both thrombotic and hemorrhagic events are described in the perinatal period in these neonates. The aim of this study was to systematically review the literature on the laboratory studies used to evaluate the hemostatic system of the IUGR small for gestational age neonate. We reviewed the current literature via PubMed and Scopus until September 2022. Following our inclusion/exclusion criteria, we finally included 60 studies in our review. Thrombocytopenia, characterized as hyporegenerative and a kinetic upshot of reduced platelet production due to in utero chronic hypoxia, was the main finding of most studies focusing on growth-restricted neonates, in most cases is mild and usually resolves spontaneously with the first 2 weeks of life. In regard to coagulation, growth-restricted newborns present with prolonged standard coagulation tests. Data regarding coagulation factors, fibrinolytic system, and anticoagulant proteins are scarce and conflicting, mainly due to confounding factors. As thromboelastography/rotational thromboelastometry (TEG/ROTEM) provides a more precise evaluation of the in vivo coagulation process compared with standard coagulation tests, its use in transfusion guidance is fundamental. Only one study regarding TEG/ROTEM was retrieved from this population, where no difference in ROTEM parameters compared with appropriate for gestational age neonates was found. Despite the laboratory aberrations, no correlation could be achieved with clinical manifestations of bleeding or thrombosis in the studies included. More studies are needed to assess hemostasis in IUGR neonates and guide targeted therapeutic interventions.
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Coagulation in pediatric extracorporeal membrane oxygenation: A systematic review of studies shows lack of standardized reporting
Drop J, Van Den Helm S, Monagle P, Wildschut E, de Hoog M, Gunput STG, Newall F, Dalton HJ, MacLaren G, Ignjatovic V, et al
Research and practice in thrombosis and haemostasis. 2022;6(2):e12687
Abstract
OBJECTIVES Extracorporeal membrane oxygenation (ECMO) involves complex coagulation management and frequent hemostatic complications. ECMO practice between centers is variable. To compare results between coagulation studies, standardized definitions and clear documentation of ECMO practice is essential. We assessed how study population, outcome definitions, and ECMO-, coagulation-, and transfusion-related parameters were described in pediatric ECMO studies. DATA SOURCES Embase, Medline, Web of Science, Cochrane Library and Google Scholar. STUDY SELECTION English original studies of pediatric ECMO patients describing hemostatic tests or outcome. DATA EXTRACTION Eligibility was assessed following PRISMA guidelines. Study population, outcome and ECMO-, coagulation, and transfusion parameters were summarized. DATA SYNTHESIS A total of 107 of 1312 records were included. Study population parameters most frequently included (gestational) age (79%), gender (60%), and (birth) weight (59%). Outcomes, including definitions of bleeding (29%), thrombosis (15%), and survival (43%), were described using various definitions. Description of pump type, oxygenator and cannulation mode occurred in 49%, 45%, and 36% of studies, respectively. The main coagulation test (53%), its reference ranges (49%), and frequency of testing (24%) were the most prevalent reported coagulation parameters. The transfusion thresholds for platelets, red blood cells, and fibrinogen were described in 27%, 18%, and 18% of studies, respectively. CONCLUSIONS This systematic review demonstrates a widespread lack of detail or standardization of several parameters in coagulation research of pediatric ECMO patients. We suggest several parameters that might be included in future coagulation studies. We encourage the ECMO community to adopt and refine this list of parameters and to use standardized definitions in future research.
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Outcome measures used in clinical research evaluating pre-hospital blood component transfusion in traumatically injured bleeding patients: A systematic review
Tucker H, Avery P, Brohi K, Davenport R, Griggs J, Weaver A, Green L
The journal of trauma and acute care surgery. 2021
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Editor's Choice
Abstract
BACKGROUND Trial outcomes should be relevant to all stakeholders, and allow assessment of interventions' efficacy and safety at appropriate timeframes. There is no consensus regarding outcome measures in the growing field of pre-hospital trauma transfusion research. Harmonization of future clinical outcome reporting is key to facilitate inter-study comparisons and generate cohesive, robust evidence to guide practice. OBJECTIVES To evaluate outcome measures reported in pre-hospital trauma transfusion trials. METHODS Data Sources, Eligibility Criteria, Participants and InterventionsWe conducted a scoping systematic review to identify the type, number and definitions of outcomes reported in randomised controlled trials, prospective and retrospective observational cohort studies investigating pre-hospital blood component transfusion in adult and paediatric patients with traumatic haemorrhage. Electronic database searching of PubMed, Embase, Web of Science, Cochrane, OVID, clinical trials.gov, and the Transfusion Evidence Library was completed in accordance with PRISMA guidelines.Study Appraisal and Synthesis MethodsTwo review authors independently extracted outcome data. Unique lists of salutogenic (patient-reported health and wellbeing outcomes) and non-salutogenic focused outcomes were established. RESULTS 3,471 records were identified. 34 studies fulfilled inclusion criteria: four military (n = 1,566 patients) and 30 civilian (n = 14,398 patients), all between 2000 and 2020. 212 individual non-patient-reported outcomes were identified, which collapsed into 20 outcome domains with varied definitions and timings. All primary outcomes measured effectiveness, rather than safety or complications. 69% reported mortality, with 11 different definitions. No salutogenic outcomes were reported. LIMITATIONS The review is limited by a lack of high-grade prospective comparative trials with clear predefined primary outcomes. CONCLUSION AND IMPLICATIONS OF KEY FINDINGS There is heterogeneity in outcome reporting and definitions, an absence of patient-reported outcome, and an emphasis on clinical effectiveness rather than safety or adverse events in pre-hospital trauma transfusion trials. We recommend stakeholder consultation and a Delphi process to develop a clearly defined minimum core outcome set for pre-hospital trauma transfusion trials. SYSTEMATIC REVIEW REGISTRATION NUMBER This review was prospectively registered with PROSPERO (CRD42019131406). LEVEL OF EVIDENCE II. STUDY TYPE Scoping Systematic Review.
PICO Summary
Population
Adult and paediatric patients with traumatic haemorrhage (34 studies, n= 15,964).
Intervention
Systematic review to identify the type, number and definitions of outcomes reported in pre-hospital trauma transfusion research.
Comparison
Outcome
212 individual non-patient-reported outcomes were identified, which collapsed into 20 outcome domains with varied definitions and timings. All primary outcomes measured effectiveness, rather than safety or complications. 69% reported mortality, with 11 different definitions. No salutogenic outcomes were reported.
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Accuracy of risk tools to predict critical bleeding in major trauma: a systematic review with meta-analysis
Gianola S, Castellini G, Biffi A, Porcu G, Napoletano A, Coclite D, D'Angelo D, Fauci AJ, Iacorossi L, Latina R, et al
The journal of trauma and acute care surgery. 2021
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Editor's Choice
Abstract
BACKGROUND Early detection of critical bleeding by accurate tools can help ensure rapid delivery of blood products to improve outcomes in major trauma patients. We conducted a systematic review to evaluate the accuracy of risk tools to predict critical bleeding in patients with major trauma. METHODS PubMed, Embase and CENTRAL were searched up to February 2021 for studies investigating risk tools to predict critical bleeding for major trauma people in pre-hospital and emergency department. We followed the PRISMA-DTA guidelines. Two independent authors included studies, extracted data, appraised the quality using the Quality Assessment of Diagnostic Accuracy Studies-2 and assessed the certainty of evidence using thee Grading of Recommendations Assessment, Development and Evaluation methodology. Sensitivity, specificity and the Receiver Operating Characteristics curve for all selected triage tools. RESULTS Eighty-nine observational studies for adults and 12 observational studies for children met our inclusion criteria. In adults, we found 23 externally validated and 28 un-validated tools; in children, 3 externally validated tools and 5 un-validated. In the externally validated tools, we identified those including clinical, laboratory and ultrasound assessments. Among tools including only a clinical assessment, the Shock Index showed high sensitivity and specificity with the Certainty of Evidence ranging from very low to moderate in adults, as well as Shock Index Pediatric Age-adjusted (SIPA) with a moderate Certainty of Evidence. We found that tools using clinical, laboratory and ultrasound assessments were overall more accurate than those tools without all three components. CONCLUSIONS Clinicians should consider risk tools to predict critical bleeding in a time-sensitive setting like major life threatening trauma. The Shock index and SIPA are easy and handy tools to predict critical bleeding in the pre-hospital setting. In the emergency department, however, many other tools can be utilized which include laboratory and ultrasound assessments, depending on staff experience and resources. LEVEL OF EVIDENCE Systematic review, diagnostic Level III.
PICO Summary
Population
Adults and children with major trauma (101 studies).
Intervention
Systematic review to identify the most accurate risk tools to predict critical bleeding.
Comparison
Outcome
Twenty-three externally validated and 28 un-validated tools were found for adults, and 3 externally validated tools and 5 un-validated, for children. Among tools including only a clinical assessment, the Shock Index showed high sensitivity and specificity with the Certainty of Evidence ranging from very low to moderate in adults, as well as Shock Index Paediatric Age-adjusted with a moderate Certainty of Evidence. It was found that tools using clinical, laboratory and ultrasound assessments were overall more accurate than those tools without all three components.
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Metrics of shock in pediatric trauma patients: A systematic search and review
Alberto, E. C., McKenna, E., Amberson, M. J., Tashiro, J., Donnelly, K., Thenappan, A. A., Tempel, P. E., Ranganna, A. S., Keller, S., Marsic, I., et al
Injury. 2021;52(10):3166-3172
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Free full text
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Abstract
INTRODUCTION Shock-index (SI) and systolic blood pressure (SBP) are metrics for identifying children and adults with hemodynamic instability following injury. The purpose of this systematic review was to assess the quality of these metrics as predictors of outcomes following pediatric injury. MATERIALS AND METHODS We conducted a literature search in Pubmed, SCOPUS, and CINAHL to identify studies describing the association between shock metrics on the morbidity and mortality of injured children and adolescents. We used the data presented in the studies to calculate the sensitivity and specificity for each metric. This study was registered with Prospero, protocol CRD42020162971. RESULTS Fifteen articles met the inclusion criteria. seven studies evaluated SI or SIPA score, an age-corrected version of SI, as predictors of outcomes following pediatric trauma, with one study comparing SIPA score and SBP and one study comparing SI and SBP. The remaining eight studies evaluated SBP as the primary indicator of shock. The median sensitivity for predicting mortality and need for blood transfusion was highest for SI, followed by SIPA, and then SBP. The median specificity for predicting these outcomes was highest for SBP, followed by SIPA, and then SI. CONCLUSIONS Common conclusions were that high SIPA scores were more specific than SI and more sensitive than SBP. SIPA score had better discrimination for severely injured children compared to SI and SBP. An elevated SIPA was associated with a greater need for blood transfusion and higher in-hospital mortality. SIPA is specific enough to exclude most patients who do not require a blood transfusion.
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Challenges in Maintaining the Hemostatic Balance in Children Undergoing Extracorporeal Membrane Oxygenation: A Systematic Literature Review
Drop JGF, Wildschut ED, Gunput STG, de Hoog M, van Ommen CH
Frontiers in pediatrics. 2020;8:612467
Abstract
Background: Despite advances in technology and clinical experience, the incidence of hemostatic complications, including bleeding and thrombosis, remains high in children supported with extracorporeal membrane oxygenation (ECMO). These hemostatic complications are important to prevent, since they are associated with increased morbidity and mortality. This systematic literature review aims to outline the most important risk factors for hemostatic complications in children undergoing ECMO treatment, to summarize the reported alternative anticoagulant drugs used in pediatric ECMO and to describe studied associations between coagulation tests and hemostatic complications. Methods: A literature search was performed in Embase, Medline, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and Google Scholar in February 2020. Included studies were studies evaluating children (<18 years old) treated with ECMO, and studies evaluating risk factors for hemostatic complications, alternative anticoagulants, or the association between coagulation tests and hemostatic complications. Results: Out of 1,152 articles, 35 studies were included. Thirteen out of 49 risk factors were investigated in three or more studies. Most consistent results were found regarding ECMO duration and pH. However, evidence for risk factors was equivocal in the majority of studies, which is explained by the variability of populations studied, definitions of hemostatic complications, ECMO circuits, anticoagulation protocols, transfusion triggers and monitoring of anticoagulation. Five studies described alternative anticoagulants, including bivalirudin (n = 3), argatroban (n = 1) and FUT (n = 1). Higher anti-factor Xa levels were associated with less clotting events in one of nine studies, investigating the association between tests and hemostatic complications. Two studies revealed an association between anti-factor Xa assay-based protocols and a decreased number of transfusions, bleedings and need for circuit change. Conclusion: Studies regarding risk factors showed conflicting results and a few retrospective studies reported the use of new anticoagulants and data on coagulation tests in relation to hemostatic complications. To decrease hemostatic complications in ECMO children, prospective multicenter studies are needed with clear bleeding and thrombotic definitions, and the best possible standardization of ECMO circuits used, anticoagulation protocols, and transfusion triggers.
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Outcome of Early Hemostatic Intervention in Children With Sepsis and Nonovert Disseminated Intravascular Coagulation Admitted to PICU: A Randomized Controlled Trial
El-Nawawy AA, Elshinawy MI, Khater DM, Moustafa AA, Hassanein NM, Wali YA, Nazir HF
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2020
Abstract
Critically ill children with sepsis may develop catastrophic thrombotic and hemorrhagic syndrome of disseminated intravascular coagulopathy as a final common pathway. OBJECTIVES Evaluation of the outcome of early hemostatic management of disseminated intravascular coagulopathy in patients with severe sepsis/septic shock admitted to PICU, before the development of clinically overt disseminated intravascular coagulopathy. DESIGN Prospective interventional, open label randomized controlled clinical trial. SETTING PICU at Alexandria University Children's Hospital. PATIENTS The study included 80 patients with proven severe sepsis/septic shock in nonovert disseminated intravascular coagulopathy stage. They were randomly assigned into two groups (group 1 and group 2). INTERVENTIONS Specific intervention was applied for group 1 (plasma transfusion, low-dose unfractionated heparin, and tranexamic acid). MEASUREMENTS All patients had assessment of Pediatric Index of Mortality 2 score, Pediatric Logistic Organ Dysfunction score, inotropic score, routine laboratory, and hemostatic tests including fibrin degradation products and D-dimers. Disseminated intravascular coagulopathy risk assessment scores were calculated on daily basis. RESULTS Mortality rate was significantly higher in group 2. Progression to overt disseminated intravascular coagulopathy was significantly more common among group 2 patients than group 1 (45% and 10%, respectively) (p < 0.0001). Disseminated intravascular coagulopathyRisk Assessment Scores were significantly higher on the second and fifth days among group 2 patients. The initial specific hemostatic intervention was the only significant predictor of survival and prevention of progression to overt disseminated intravascular coagulopathy. CONCLUSIONS Our results suggest that early use of a combination of fresh frozen plasma transfusion, low-dose heparin, and tranexamic acid in children with severe sepsis/septic shock in the "window of opportunity" before the development of overt disseminated intravascular coagulopathy stage was associated with better outcome for survival and prevention of progression to overt disseminated intravascular coagulopathy, with no increase in bleeding risk. Larger multicenter studies are needed to further prove this practice.
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Effect of Umbilical Cord Blood Sampling versus Admission Blood Sampling on Requirement of Blood Transfusion in Extremely Preterm Infants: A Randomized Controlled Trial
Balasubramanian H, Malpani P, Sindhur M, Kabra NS, Ahmed J, Srinivasan L
The Journal of pediatrics. 2019
Abstract
OBJECTIVE To evaluate the effect of blood sampling from the placental end of the umbilical cord compared with initial blood sampling from neonates, on the need for first packed red blood cell transfusion in extremely preterm infants. We hypothesized that cord blood sampling could delay the time to first blood transfusion. STUDY DESIGN In this single-center, assessor blind, randomized controlled trial, we included extremely low birth weight neonates <28 weeks of gestational age at birth. Five milliliter of blood for initial laboratory investigations was collected either from the placental end of the umbilical cord (study group) or from the neonate upon neonatal intensive care unit admission (control group). Both groups received similar anemia prevention strategies. The primary outcome was the time (in days) to the first packed red blood cell transfusion, and was compared using survival analysis. RESULTS Eighty neonates were enrolled. The time to first transfusion was significantly delayed in the cord sampling group (30 vs 14 days, hazard ratio: 0.44, [95% CI 0.27-0.72], P < .001). Fewer neonates in the cord sampling group were transfused in the first 28 days of life (30% vs 75%, P < .001). Overall transfusion requirements and other clinical outcomes were similar in the groups. CONCLUSIONS Initial blood sampling from placental end of umbilical cord, when combined with anemia prevention strategies, significantly prolonged the time to first transfusion and reduced the need for early transfusions among extremely premature neonates. TRIAL REGISTRATION Ctri.nic.in/ (CTRI/2017/04/008320).
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Massive Transfusion in the Pediatric Population: A Systematic Review and Summary of Best-Evidence Practice Strategies
Kamyszek RW, Leraas HJ, Reed C, Ray CM, Nag UP, Poisson JL, Tracy ET
The journal of trauma and acute care surgery. 2019
Abstract
BACKGROUND Pediatric patients require massive transfusion (MT) in a variety of settings. Multiple studies of adult MT support balanced ratio transfusion to improve outcomes, however it is unclear if these findings can be extrapolated to pediatric populations. The use of balanced transfusion ratios, MT protocols, hemostatic adjuncts, and even the definition of a MT in children are all open questions. This review presents details of care from current practices in pediatric MT and summarizes practice strategies while providing insight from our single center experience. METHODS PubMed, EMBASE, and Web of Science were searched using MeSH index and free text terms for articles from 1946 to 2017. Articles were independently reviewed by two reviewers. Studies were assessed for definition of MT, factors predicting MT, MT complications, blood product ratios, hemostatic adjuncts, protocol logistics, and clinical outcomes. RESULTS A heterogeneous composite of 29 articles was included in the analysis. Of these, 45% reported a formal transfusion protocol or adopted one during the study. Seven unique definitions of pediatric MT were reported; the most common was >1 total blood volume within 24 hours. A total of 18,369 patients were assessed, and 1,163 received MT (6.3%). Overall mortality for patients requiring MT in studies reporting mortality was high (range 14.7% to 51.2%). We identified 14 patients receiving MT at our center with an age range of 8 months to 18 years and average transfusion of 38.1 ml/kg RBC (range: 22.1 ml/kg to 156.7 ml/kg). CONCLUSIONS Current practices of pediatric MT demonstrate a variety of site-specific interventions with a persistently high mortality rate. A national focus on improving techniques of massive transfusion in children has the potential to save the lives of these children. LEVEL OF EVIDENCE Level IV and V, Systematic Review.
