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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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Causes and Risk Factors of Pediatric Spontaneous Intracranial Hemorrhage-A Systematic Review
Ciochon UM, Bindslev JBB, Hoei-Hansen CE, Truelsen TC, Larsen VA, Nielsen MB, Hansen AE
Diagnostics (Basel, Switzerland). 2022;12(6)
Abstract
Previous studies suggest that the most common cause of spontaneous intracerebral hemorrhage in children and adolescents is arteriovenous malformations (AVMs). However, an update containing recently published data on pediatric spontaneous intracranial hemorrhages is lacking. The aim of this study is to systematically analyze the published data on the etiologies and risk factors of pediatric spontaneous intracranial hemorrhage. This systematic review was performed in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A search in PubMed, Embase, Scopus, Web of Science and Cochrane Library was conducted aiming for articles published in year 2000 and later, containing data on etiology and risk factors of spontaneous intracranial hemorrhages in unselected cohorts of patients aged between 1 month and 18 years. As a result, forty studies were eligible for data extraction and final analysis. These included 7931 children and adolescents with 4009 reported etiologies and risk factors. A marked variety of reported etiologies and risk factors among studies was observed. Vascular etiologies were the most frequently reported cause of pediatric spontaneous intracranial hemorrhages (n = 1727, 43.08% of all identified etiologies or risk factors), with AVMs being the most common vascular cause (n = 1226, 70.99% of all vascular causes). Hematological and systemic causes, brain tumors, intracranial infections and cardiac causes were less commonly encountered risk factors and etiologies.
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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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Hemostasis in Neonates with Perinatal Hypoxia-Laboratory Approach: A Systematic Review
Tsaousi M, Iliodromiti Z, Iacovidou N, Karapati E, Sulaj A, Tsantes AG, Petropoulou C, Boutsikou T, Tsantes AE, Sokou R
Seminars in thrombosis and hemostasis. 2022
Abstract
Birth asphyxia, with an estimated prevalence of 1 to 6 per 1,000 live births, may lead to multiorgan dysfunction due to impaired oxygen and/or blood supply to various organ systems, including the hemostatic system. Coagulopathy, a common complication of perinatal asphyxia, has been described since the 1960s. The aim of this study was to systematically review the literature for records on the use of hemostasis tests in the evaluation of coagulation disorders, in neonates who had suffered from perinatal hypoxia or asphyxia. We identified published studies by searching PubMed and Scopus, up until April 2022. The literature search retrieved 37 articles fulfilling the inclusion criteria of the review. According to the bibliography, thrombocytopenia is commonly associated with perinatal hypoxia/asphyxia. The thrombocytopenia is usually described as mild and platelets return to normal levels by the 10th day of life. Additionally, hypoxic neonates usually present with a hypocoagulable profile, as reflected by the prolongation of standard coagulation tests, including prothrombin time, activated partial thromboplastin time, and international normalized ratio, findings commonly associated with disseminated intravascular coagulation, and by the reduction of the levels of the physiologic inhibition of coagulation system. A few studies thus far using ROTEM/TEG in hypoxic neonates have come to the same conclusion as well; hypoxic newborns seem to be characterized by a hypocoagulable profile compared with healthy neonates. It should be emphasized, however, that standard coagulation tests provide only a rough estimation of the true bleeding or thrombotic risk of hypoxic neonates. On the contrary, viscoelastic methods seem to be more precise in the early detection of hemostasis disorders in the neonatal population. However, until now, there was uncertainty as to the most appropriate coagulation assays for diagnosis and management of coagulation derangement in neonates with perinatal hypoxia indicating the need for further research on this field.
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Non-Invasive Prenatal Fetal Blood Group Genotype and Its Application in the Management of Hemolytic Disease of Fetus and Newborn: Systematic Review and Meta-Analysis
Alshehri AA, Jackson DE
Transfusion medicine reviews. 2021
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Editor's Choice
Abstract
Hemolytic disease of fetus and newborn (HDFN) imposes great healthcare burden being associated with maternal alloimmunization against parental-inherited fetal red blood cell antigens causing fetal anemia or death. Noninvasive prenatal analysis (NIPT) provides safe fetal RHD genotyping for early identification of risk pregnancies and proper management guidance. We aimed to conduct systematic review and meta-analysis on NIPT's beneficial application, in conjunction with quantitative maternal alloantibody analysis, for early diagnosis of pregnancies at risk. Search for relevant articles was done in; PubMed/Medline, Scopus, and Ovid (January 2006April 2020), including only English-written articles reporting reference tests and accuracy data. Nineteen eligible studies were critically appraised. NIPT was estimated highly sensitive/specific for fetal RHD genotyping beyond 11-week gestation. Amplifications from ≥2 exons are optimum to increase accuracy. NIPT permits cost-effectiveness, precious resources sparing, and low emotional stress. Knowledge of parental ethnicity is important for correct NIPT result interpretations and quantitative screening. Cut-off titer ≥8-up-to-32 is relevant for anti-D alloantibodies, while, lower titer is for anti-K. Alloimmunization is influenced by maternal RHD status, gravida status, and history of adverse obstetrics. In conclusion, NIPT allows evidence-based provision of routine anti-D immunoprophylaxis and estimates potential fetal risks for guiding further interventions. Future large-scale studies investigating NIPT's non-RHD genotyping within different ethnic groups and in presence of clinically significant alloantibodies are needed.
PICO Summary
Population
Women whose pregnancy was at risk of haemolytic disease of foetus and new born (HDFN), (19 studies).
Intervention
Systematic review and meta-analysis on non-invasive prenatal analysis (NIPT) in conjunction with quantitative maternal alloantibody analysis.
Comparison
Outcome
NIPT was estimated highly sensitive/specific for foetal RHD genotyping beyond 11-week gestation. Amplifications from ≥2 exons were optimum to increase accuracy. NIPT permitted cost-effectiveness and was associated with low emotional stress. Knowledge of parental ethnicity was important for correct NIPT result interpretations and quantitative screening. Cut-off titre ≥8-up-to-32 was relevant for anti-D alloantibodies, while, lower titre was for anti-K. Alloimmunisation was influenced by maternal RHD status, gravida status, and history of adverse obstetrics.
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A scoping review of transition interventions for young adults with sickle cell disease
Viola A, Porter J, Shipman J, Brooks E, Valrie C
Pediatric blood & cancer. 2021;:e29135
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Abstract
Standardized programming for individuals with sickle cell disease (SCD) transitioning from pediatric to adult-centered care does not currently exist, resulting in high rates of mortality and morbidity. This scoping review examines and evaluates the current literature on SCD transition programs and interventions. Eligible studies described an existing program for individuals with SCD aged 12-29 years preparing to transition. The Evidence Project risk-of-bias tool was used to assess article quality. We identified 30 eligible articles, of which, only two were randomized controlled trials. Many studies have incomplete reports of feasibility information, such as completion rates, patient characteristics, and attrition; all studies were limited to a single institution; and most studies were rated high for risk of bias. Progress has been made in designing and gathering initial evaluation data for SCD transition programs; however, there is a need for higher quality studies, consistent assessment, and better dissemination of programs.
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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
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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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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Evidence-based interventions implemented in low-and middle-income countries for sickle cell disease management: A systematic review of randomized controlled trials
Gyamfi J, Ojo T, Epou S, Diawara A, Dike L, Adenikinju D, Enechukwu S, Vieira D, Nnodu O, Ogedegbe G, et al
PloS one. 2021;16(2):e0246700
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Editor's Choice
Abstract
BACKGROUND Despite ~90% of sickle cell disease (SCD) occurring in low-and middle-income countries (LMICs), the vast majority of people are not receiving evidence-based interventions (EBIs) to reduce SCD-related adverse outcomes and mortality, and data on implementation research outcomes (IROs) and SCD is limited. This study aims to synthesize available data on EBIs for SCD and assess IROs. METHODS We conducted a systematic review of RCTs reporting on EBIs for SCD management implemented in LMICs. We identified articles from PubMed/Medline, Global Health, PubMed Central, Embase, Web of Science medical subject heading (MeSH and Emtree) and keywords, published from inception through February 23, 2020, and conducted an updated search through December 24, 2020. We provide intervention characteristics for each study, EBI impact on SCD, and evidence of reporting on IROs. MAIN RESULTS 29 RCTs were analyzed. EBIs identified included disease modifying agents, supportive care agents/analgesics, anti-malarials, systemic treatments, patient/ provider education, and nutritional supplements. Studies using disease modifying agents, nutritional supplements, and anti-malarials reported improvements in pain crisis, hospitalization, children's growth and reduction in severity and prevalence of malaria. Two studies reported on the sustainability of supplementary arginine, citrulline, and daily chloroquine and hydroxyurea for SCD patients. Only 13 studies (44.8%) provided descriptions that captured at least three of the eight IROs. There was limited reporting of acceptability, feasibility, fidelity, cost and sustainability. CONCLUSION EBIs are effective for SCD management in LMICs; however, measurement of IROs is scarce. Future research should focus on penetration of EBIs to inform evidence-based practice and sustainability in the context of LMICs. CLINICAL TRIAL REGISTRATION This review is registered in PROSPERO #CRD42020167289.
PICO Summary
Population
Children and adults with sickle cell disease (SCD) in 14 low- and middle-income countries, (30 studies).
Intervention
Evidence-based interventions including: disease modifying agents, supportive care agents/analgesics, anti-malarials, systemic treatments (e.g., red blood cell transfusions), patient/provider education, and nutritional supplements.
Comparison
Placebo or comparator intervention
Outcome
Studies using disease modifying agents, nutritional supplements, and anti-malarials reported improvements in pain crisis, hospitalization, children's growth and reduction in severity and prevalence of malaria. Two studies reported on the sustainability of supplementary arginine, citrulline, and daily chloroquine and hydroxyurea for SCD patients. Only 13 studies (44.8%) provided descriptions that captured at least three of the eight implementation research outcomes. There was limited reporting of acceptability, feasibility, fidelity, cost and sustainability.
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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.