International Survey of the Management of Disseminated Intravascular Coagulation Among Pediatric and Neonatal Health Care Practitioners.

The International Society of Thrombosis and Hemostasis (ISTH) provides objective disseminated intravascular coagulation (DIC) measurement through diagnostic criteria validated in adults. The applicability of these criteria in pediatric and neonatal DIC is controversial and unvalidated. Primary objective: to evaluate current practice in pediatric and neonatal DIC management among different specialties. Secondary objective: to understand the potential impact of developmental hemostasis on DIC laboratory evaluation. We performed a multicenter survey between January and September 2016. The questionnaire was distributed internationally through professional societies. In all, 211 responses were received, of which 160 were full responses and 51 were partial. Overall, 85% of respondents practiced in tertiary academic centers; 70% practiced in pediatric-only hospitals. The majority of respondents (42%) used their personal clinical experience in the management of DIC. Sixty percent of respondents treated DIC until the resolution of both clinical and laboratory parameters. Laboratory investigations were monitored in the majority of DIC cases without thrombosis or bleeding (80%); age-specific reference ranges for tests were lacking in 20% of pediatric-only hospitals and 35% of combined pediatric/adult hospitals. Adherence to standardized DIC guidelines was poor but varied by geographical location. This survey reveals variable practices among pediatricians in the management of DIC. Further studies are needed to validate the DIC diagnostic criteria in children.

Changes in von Willebrand Factor Multimers, Concentration, and Function During Pediatric Extracorporeal Membrane Oxygenation.

OBJECTIVES: To investigate changes in von Willebrand factor (VWF) concentration, function, and multimers during pediatric extracorporeal membrane oxygenation (ECMO) and determine whether routine monitoring of VWF during ECMO would be useful in predicting bleeding. DESIGN: Prospective observational study of pediatric ECMO patients from April 2017 to May 2019. SETTING: The PICU in a large, tertiary referral pediatric ECMO center. PATIENTS: Twenty-five neonates and children (< 18 yr) supported by venoarterial ECMO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Arterial blood samples were collected within 24 hours pre-ECMO, daily for the first 5 days of ECMO, every second day until decannulation, and 24 hours post-ECMO. The STA R Max analyzer was used to measure VWF antigen (VWF:Ag) and ristocetin cofactor (VWF:RCo) activity. VWF collagen binding (VWF:CB) was measured using an enzyme-linked immunosorbent assay. VWF multimers were measured using the semi-automated Hydragel 11 VWF Multimer assay. Corresponding clinical data for each patient was also recorded. A total of 25 venoarterial ECMO patients were recruited (median age, 73 d; interquartile range [IQR], 3 d to 1 yr). The median ECMO duration was 4 days (IQR, 3-8 d) and 15 patients had at least one major bleed during ECMO. The percentage of high molecular weight multimers (HMWM) decreased and intermediate molecular weight multimers increased while patients were on ECMO, irrespective of a bleeding status. VWF:Ag increased and the VWF:RCo/VWF:Ag and VWF:CB/VWF:Ag ratios decreased while patients were on ECMO compared with the baseline pre-ECMO samples and healthy children. CONCLUSIONS: Neonates and children on ECMO exhibited a loss of HMWM and lower VWF:CB/VWF:Ag and VWF:RCo/VWF:Ag ratios compared with healthy children, irrespective of major bleeding occurring. Therefore, monitoring VWF during ECMO would not be useful in predicting bleeding in these patients and changes to other hemostatic factors should be investigated to further understand bleeding during ECMO.

Platelet Phenotype and Function Changes With Increasing Duration of Extracorporeal Membrane Oxygenation.

OBJECTIVES: To investigate platelet pathophysiology associated with pediatric extracorporeal membrane oxygenation (ECMO). DESIGN: Prospective observational study of neonatal and pediatric ECMO patients from September 1, 2016, to December 31, 2019. SETTING: The PICU in a large tertiary referral pediatric ECMO center. PATIENTS: Eighty-seven neonates and children (< 18 yr) supported by ECMO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Arterial blood samples were collected on days 1, 2, and 5 of ECMO and were analyzed by whole blood flow cytometry. Corresponding clinical data for each patient was also recorded. A total of 87 patients were recruited (median age, 65 d; interquartile range [IQR], 7 d to 4 yr). The median duration of ECMO was 5 days (IQR, 3-8 d) with a median length of stay in PICU and hospital of 18 days (IQR, 10-29 d) and 35 days (IQR, 19-75 d), respectively. Forty-two patients (48%) had at least one major bleed according to a priori determined definitions, and 12 patients (14%) had at least one thrombotic event during ECMO. Platelet fibrinogen receptor expression decreased (median fluorescence intensity [MFI], 29,256 vs 26,544; p = 0.0005), while von Willebrand Factor expression increased (MFI: 7,620 vs 8,829; p = 0.0459) from day 2 to day 5 of ECMO. Platelet response to agonist, Thrombin Receptor Activator Peptide 6, also decreased from day 2 to day 5 of ECMO, as measured by binding with anti-P-selectin, PAC-1 (binds activated GPIIb/IIIa), and anti-CD63 monoclonal antibodies (P-selectin area under the curve [AUC]: 63.46 vs 42.82, respectively, p = 0.0022; PAC-1 AUC: 93.75 vs 74.46, p = 0.0191; CD63 AUC: 55.69 vs 41.76, p = 0.0020). CONCLUSIONS: The loss of platelet response over time may contribute to bleeding during ECMO. These novel insights may be useful in understanding mechanisms of bleeding in pediatric ECMO and monitoring platelet markers clinically could allow for prediction or early detection of bleeding and thrombosis.

Age partitioned and continuous upper reference limits for Ortho VITROS High Sensitivity Troponin I in a healthy paediatric cohort.

OBJECTIVES: In adults, the elevation of cardiac troponin (cTn) above the 99th percentile upper reference limit defines myocardial injury. The use and interpretation of cTn in a paediatric population, however, is difficult given the 99th percentile for different assays is not well established. Using paediatric blood samples from healthy neonates, infants and children we derived continuous and partitioned 97.5th and 99th percentiles for the Ortho VITROS hs-TnI assay. METHODS: A total of 328 samples for infants, children and adolescents aged 0-17.8 years were obtained. Age partitioned reference limits were derived in accordance with CLSI EP28-A3C. Continuous reference limits were established as described previously by the HAPPI Kids Study team. RESULTS: hs-TnI as measured by the Ortho VITROS Assay is highly elevated above the adult 99th percentile at birth and declines to lower levels within the first 6 months of life. The 99th centile upper reference limit for ages 0-3 months was 72 ng/L (90% CI: 52-91) and 9 ng/L (90% CI: 5.2-17.4) for ages 3 months to 18 years. Continuous upper 99th centile reference limits were comparable. CONCLUSIONS: Partitioned and continuous 99th percentiles for hs-TnI were derived for the new Ortho VITROS assay in healthy neonates and older children. This will assist clinicians to appropriately assess for the presence of myocardial injury in this population.

Age-related differences in SARS-CoV-2 binding factors: An explanation for reduced susceptibility to severe COVID-19 among children?

CONTEXT: In contrast with other respiratory viruses, children infected with SARS-CoV-2 are largely spared from severe COVID-19. OBJECTIVES: To critically assess age-related differences in three host proteins involved in SARS-CoV-2 cellular entry: angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2) and furin. METHODS: We systematically searched Medline, Embase, and PubMed databases for relevant publications. Studies were eligible if they evaluated ACE2, TMPRSS2 or furin expression, methylation, or protein level in children. RESULTS: Sixteen papers were included. Age-dependent differences in membrane-bound and soluble ACE2 were shown in several studies, with ACE2 expression increasing with age. TMPRSS2 and furin are key proteases involved in SARS-CoV-2 spike protein cleavage. TMPRSS2 expression is increased by circulating androgens and is thus low in pre-pubertal children. Furin has not currently been well researched. LIMITATIONS: High levels of study heterogeneity. CONCLUSIONS: Low expression of key host proteins may partially explain the reduced incidence of severe COVID-19 among children, although further research is needed.

Recombinant Factor VIIa in Pediatric Cardiac Surgery.

OBJECTIVES: Recombinant activated factor VIIa (rVIIa) is used off-label for refractory bleeding after cardiac surgery. This study reviewed the indications, usage rates, and complications of rVIIa. DESIGN: A retrospective case-control observational study. SETTING: A single quaternary pediatric hospital. PARTICIPANTS: All children undergoing cardiac surgery with cardiopulmonary bypass over a three-year period. INTERVENTIONS: Administration of rVIIa as rescue therapy for refractory bleeding after weaning from cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: Onethousand, five hundred fifteen cardiopulmonary bypass procedures were reviewed. Patients receiving rVIIa were each matched to two control patients by age, procedure type, and bypass time. Data collected included weight, crossclamp time, anticoagulant and antifibrinolytic dose, return to the operating room for bleeding, thrombotic events, and extracorporeal membrane oxygenation (ECMO) circuit interventions. Forty-two patients received rVIIa (2.8%). Major systemic thrombotic complications were observed in 19% (controls 12.5%) of patients; 80% of recombinant factor VIIa patients requiring postoperative ECMO had interventions for circuit thrombosis (controls 31.25%); 4.76% of rVIIa recipients required reexploration for intractable bleeding (controls 1.39%). CONCLUSIONS: This study added to understanding regarding the use of recombinant factor VIIa in pediatric cardiac surgery and reported increased thrombotic complications, especially for children who progress to ECMO. Prospective studies to better understand the pathophysiology of coagulopathy and hemorrhage in pediatric cardiac surgery and the role of hemostatic agents, such as rVIIa, are required.

Fatigue Following Pediatric Arterial Ischemic Stroke: Prevalence and Associated Factors.

Background and Purpose: The aims of this study were to assess the prevalence of multidimensional fatigue symptoms 5 years after pediatric arterial ischemic stroke and identify factors associated with fatigue. Methods: Thirty-one children (19 males) with pediatric arterial ischemic stroke, participating in a larger prospective, longitudinal study, were recruited to this study at 5 years poststroke. Parent- and self-rated PedsQL Multidimensional Fatigue Scale scores were compared with published normative data. Associations between parent-rated PedsQL Multidimensional Fatigue Scale, demographics, stroke characteristics, and concurrent outcomes were examined. Results: Parent-rated total, general and cognitive fatigue were significantly poorer than population norms, with more than half of all parents reporting fatigue symptoms in their children. One-third of children also reported experiencing fatigue symptoms, but their ratings did not differ significantly from normative expectations, as such, all further analyses were on parent ratings of fatigue. Older age at stroke and larger lesion size predicted greater general fatigue; older age, female sex, and higher social risk predicted more sleep/rest fatigue. No significant predictors of cognitive fatigue were identified and only older age at stroke predicted total fatigue. Greater fatigue was associated with poorer adaptive functioning, motor skills, participation, quality of life, and behavior problems but not attention. Conclusions: Fatigue is a common problem following pediatric arterial ischemic stroke and is associated with the functional difficulties often seen in this population. This study highlights the importance of long-term monitoring following pediatric arterial ischemic stroke and the need for effective interventions to treat fatigue in children.

Social Cognitive Dysfunction Following Pediatric Arterial Ischemic Stroke: Evidence From a Prospective Cohort Study.

Background and Purpose: Childhood and adolescence coincide with rapid maturation of distributed brain networks supporting social cognition; however, little is known about the impact of early ischemic brain insult on the acquisition of these skills. This study aimed to examine the influence of arterial ischemic stroke (AIS) on facial emotion recognition and theory of mind (ToM) abilities of children and adolescents initially recruited to a single-center, prospective longitudinal study of recovery following AIS. Methods: The study involved 67 participants, including 30 children with AIS (mean time since stroke=5 years) and 37 age-matched typically developing controls who were assessed on measures of cognitive ToM, facial emotion recognition, and affective ToM. Acute clinical magnetic resonance imaging, including diffusion-weighted imaging sequences, were used to evaluate prospective structure-function relationships between acute lesion characteristics (size, location, and arterial territories affected) and long-term social cognitive abilities. Results: Relative to age-matched typically developing controls, children with AIS showed significantly worse performance on measures of basic facial emotion processing, cognitive ToM, and affective ToM. In univariate models, poorer ToM was associated with larger infarcts, combined cortical-subcortical pathology, and involvement of multiple arterial territories. In multivariate analyses, larger lesions and multiterritory infants were predictive of ToM processing but not facial emotion recognition. Poorer cognitive ToM predicted less frequent prosocial behavior and increased peer problems. Conclusions: Social cognitive skills appear vulnerable to disruption from early ischemic brain insult. In the first study to examine social cognition in a prospective cohort of children with AIS, our findings suggest that acute magnetic resonance imaging-based lesion characteristics may have predictive value for long-term social cognitive outcomes and may assist to identify children at elevated risk for social cognitive dysfunction.

Vaccine-induced immune thrombosis and thrombocytopenia syndrome following adenovirus-vectored severe acute respiratory syndrome coronavirus 2 vaccination: a novel hypothesis regarding mechanisms and implications for future vaccine development.

We hypothesize that thrombosis with thrombocytopenia syndrome recently described after administration of adenovirus-vectored vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurs as a result of the unique properties of the adenovirus vectors, which can have widespread biodistribution throughout the body. The antigen is delivered to megakaryocyte cells, which act as part of the primary immune system and distribute the antigen within progeny platelets, also a key component of the immune system. The interaction of the antigen induces preformed antiplatelet factor 4 (PF4) antibodies to bind to PF4-heparan sulfate complexes in the absence of exogenous heparin, at sites where the heparan sulfate concentration in the vascular glycocalyx is optimal for complex formation, causing thrombosis and thrombocytopenia as observed clinically. This hypothesis is testable in cell culture and animal models, and potentially in vivo, and if proven correct has significant implications for vaccine development and our understanding of the links between the coagulation and immune systems.

The use of proteomics for blood biomarker research in premature infants: a scoping review.

Over the last decade, the use of proteomics in the setting of prematurity has increased and has enabled researchers to successfully identify biomarkers for an array of associated morbidities. The objective of this scoping review was to identify the existing literature, as well as any knowledge gaps related to proteomic biomarker discoveries in the setting of prematurity. A scoping review was conducted using PubMed, Embase and Medline databases following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. The study selection process yielded a total of 700 records, of which 13 studies were included in this review. Most studies used a tandem Mass Spectrometry (MS/MS) proteomics approach to identify key biomarkers. The corresponding studies identified proteins associated with retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotising enterocolitis (NEC), late onset sepsis (LOS) and gestational age. This scoping review demonstrates the limited use of proteomics to identify biomarkers associated with severe complications of prematurity. Further research is warranted to identify biomarkers of other important morbidities associated with prematurity, such as intraventricular haemorrhage (IVH) and cerebral palsy, and to investigate the mechanisms associated with these outcomes.

The natural history of asymptomatic central venous catheter-related thrombosis in critically ill children.

Asymptomatic central venous catheter (CVC)-related thrombosis in children varies in incidence from 5% to 69%. The rate of acute and long-term complications, such as postthrombotic syndrome (PTS), from asymptomatic CVC-related thrombosis is unknown. This article reports the outcomes of a prospective study of 189 children in pediatric intensive care that aimed to determine the frequency of asymptomatic CVC-related thrombosis during hospital admission, and the incidence of residual CVC-related thrombosis and clinically significant PTS 2 years later. Risk factors associated with CVC-related thrombosis were also identified. This study is distinct from previous work as children identified to have asymptomatic CVC-related thrombosis were not treated (clinical team kept blinded) and the entire cohort was followed for 2 years to determine the natural history of asymptomatic thrombosis. Ultrasounds of 146 children determined a 21.9% incidence of acute CVC-related thrombosis. Two children were symptomatic. No radiological thrombosis extension or clinical embolization occurred in the 126 children assessed at follow-up. Using 2 recognized PTS scales, clinically significant PTS was reported in 2 children (1 symptomatic, 1 asymptomatic CVC-related thrombosis), however, neither had functional impairment. Cardiac arrest was a risk factor for CVC-related thrombosis during admission and femoral CVC placement was predictive of residual thrombosis 2 years later. This study challenges the notion that critically ill children with asymptomatic CVC-related thrombosis require anticoagulant treatment, as the results demonstrate that the incidence of acute or long-term complications is low. A larger confirmatory study of nontreatment of CVC-related thrombosis in critically ill children is justified.

Continuous reference intervals for leukocyte telomere length in children: the method matters.

OBJECTIVES: Children with very short telomeres commonly develop bone marrow failure and other severe diseases. Identifying the individuals with short telomeres can improve outcome of bone marrow transplantation, with accurate diagnosis requiring the use of age-matched reference intervals (RIs). This study aimed to establish RIs for telomere length (TL) in children using three commonly used methods for TL measurement. METHODS: Healthy children aged 30 days to 18 years were recruited for assessment using age as a continuous variable. Venous blood samples were collected and leukocyte TL was measured using terminal restriction fragment (TRF) analysis, quantitative PCR (QPCR) and flow cytometry with fluorescence in situ hybridization (Flow-FISH). Fractional polynomial model and quantile regression were performed to generate continuous RIs. Factors that might contribute to variation in TL, such as gender, were also examined. RESULTS: A total of 212 samples were analyzed. Continuous RIs are presented as functions of age. TRF analysis and QPCR showed significant negative correlation between TL and age (r=-0.28 and r=-0.38, p<0.001). In contrast, Flow-FISH showed no change in TL with age (r=-0.08, p=0.23). Gender did not have significant influence on TL in children. CONCLUSIONS: This study provides three options to assess TL in children by establishing method-specific continuous RIs. Choosing which method to use will depend on several factors such as amount and type of sample available and required sensitivity to age-related change.

Whole blood flow cytometry protocol for the assessment of platelet phenotype, function, and cellular interactions.

Platelets are a key component of the hemostatic system and their roles in inflammation via interactions with leukocytes have also gained attention in recent years. Changes in platelet phenotype and function can cause bleeding and/or thrombosis and, as such, monitoring platelet-specific changes is crucial to assessing hemostasis in the clinical setting. Currently, available platelet function tests such as platelet aggregometry and thromboelastography require a large volume of blood, which is a major limitation for the pediatric population. Whole blood flow cytometric analysis of platelets is increasingly utilized in recent years, primarily due to the sensitivity of this method, but also because it only requires a small amount of blood with minimal sample manipulation. We have developed a whole blood flow cytometry methodological approach that enables the assessment of platelet phenotype, function, and their interactions with monocytes and neutrophils.

Plasma Proteomic Analysis Reveals Age-Specific Changes in Platelet- and Endothelial Cell-Derived Proteins and Regulators of Plasma Coagulation and Fibrinolysis.

This post hoc study of a plasma proteomic database investigated hemostatic proteins in the context of developmental hemostasis. Twenty-seven hemostatic proteins changed expression with age, and the hemostatic profile of neonates was unique. Appreciating developmental hemostasis through proteomics may lead to more personalized medicine for hospitalized children.

Anticoagulant Heparin Mimetics via RAFT Polymerization.

Heparin, a sulfated polysaccharide derived from animal sources, is the most commonly used parenteral anticoagulant drug, but it suffers from significant safety and supply issues. Herein, we describe the preparation of heparin mimetic homo- and copolymers via the reversible addition-fragmentation chain transfer (RAFT) polymerization in water of commercially available (non-carbohydrate) sulfonated and carboxylated monomers. The anticoagulant activities of the polymers were assessed by activated partial thromboplastin time (APTT), thrombin clotting time (TCT), and for the more promising polymers, thrombin generation, antifactor Xa, and antifactor IIa assays. Sulfonated homopolymers studied herein displayed low cytotoxicity and significant anticoagulant activity in APTT, TCT, and thrombin generation assays. In addition, copolymers of sodium styrenesulfonate and acrylic acid [poly(SSS-co-AA)] displayed unprecedented antifactor IIa activity. This study demonstrates the potential of RAFT polymers as alternative anticoagulants for biomedical applications.

Reference intervals for serum cystatin C in neonates and children 30 days to 18 years old.

BACKGROUND: Serum cystatin C (CysC) is a promising biomarker of kidney function, which has higher accuracy and sensitivity when compared with creatinine. To better utilize serum CysC in clinical practice, this study aimed to establish continuous paediatric reference intervals (RIs) for serum CysC. METHODS: The study subjects consisted of healthy term neonates and children aged 30 days to 18 years. Venous blood samples were collected and serum CysC levels were measured using the immunoturbidimetric measurement principle. Fractional polynomial regression model and quantile regression was applied in the statistical analysis to generate continuous RIs. RESULTS: A total of 378 samples with equal numbers of males and females were analysed for serum CysC. No outliers were found in this analysis. The continuous RIs are presented as equations and graphical scatterplots. CONCLUSIONS: This study established continuous paediatric reference intervals (RIs) for serum CysC in healthy term neonates and children. The continuous RIs generated from this study show age-based dynamic changes as well as blood group and gender-specific differences for serum CysC. Graphical abstract.

Development and Validation of the Warfarin-Aspirin Bleeding Assessment Tool (WA-BAT) in Children.

Bleeding assessment tools (BATs) aim to screen and estimate bleeding risk in patients with inherited bleeding disorders. However, the use of BAT as a standardized measure for comparing bleeding in patients on long-term thromboprophylaxis has not yet been validated. We developed a self-administrable BAT to assess bleeding in patients undergoing long-term thromboprophylaxis with aspirin or warfarin. Eligible participants were invited to complete the warfarin-aspirin -BAT (WA-BAT) online. The WA-BAT was readministered a number of weeks later to determine intrarater reliability. The WA-BAT showed substantial intrarater reliability and assesses major and minor bleeding associated with long-term warfarin or aspirin use.

Guidelines for panel design, optimization, and performance of whole blood multi-color flow cytometry of platelet surface markers.

Flow cytometry is a valuable tool in determining the phenotype and function of platelets accurately. The emergence of platelet flow cytometry in recent years provides an attractive alternative to other platelet analytical techniques, with advantages such as requiring small volumes and being highly sensitive to minimal changes in receptor function and expression. Here we present a methodical approach encompassing the stages in the development and optimization of platelet flow cytometry panels based on our extensive experience in this area.

After an end-of-life decision: Parents' reflections on living with an end-of-life decision for their child.

AIM: Parents' role as end-of-life decision-makers for their child has become largely accepted Western health-care practice. How parents subsequently view and live with the end-of-life decision (ELD) they made has not been extensively examined. To help extend understanding of this phenomenon and contribute to care, as a part of a study on end-of-life decision-making, bereaved parents were asked about the aftermath of their decision-making. METHODS: A qualitative methodology was used. Semi-structured interviews were conducted with parents who had discussed ELDs for their child who had a life-limiting condition and had died. Data were thematically analysed. RESULTS: Twenty-five bereaved parents participated. Results indicate that parents hold multi-faceted views about their decision-making experiences. An ELD was viewed as weighty in nature, with decisions judged against the circumstances that the child and parents found themselves in. Despite the weightiness, parents reflected positively on their decisions, regarding themselves as making the right decision. Consequently, parents' comments demonstrated being able to live with their decision. When expressed, regret related to needing an ELD, rather than the actual decision. The few parents who did not perceive themselves as their child's decision-maker subsequently articulated negative reactions. Enduring concerns held by some parents mostly related to non-decisional matters, such as the child's suffering or not knowing the cause of death. CONCLUSION: Results suggest that parents can live well with the ELDs they made for their child. End-of-life decision-making knowledge is confirmed and extended, and clinical support for parents informed.

Risk of traumatic intracranial haemorrhage in children with bleeding disorders.

AIM: To assess computerised tomography (CT) use and the risk of intracranial haemorrhage (ICH) in children with bleeding disorders following a head trauma. METHODS: Design: Multicentre prospective observational study. SETTING: 10 paediatric emergency departments (ED) in Australia and New Zealand. PATIENTS: Children <18 years with and without bleeding disorders assessed in ED following head trauma between April 2011 and November 2014. INTERVENTIONS: Data collection of patient characteristics, management and outcomes. MAIN OUTCOME MEASURES: Rate of CT use and frequency of ICH on CT. RESULTS: Of 20 137 patients overall, 103 (0.5%) had a congenital or acquired bleeding disorder. CT use was higher in these patients compared with children without bleeding disorders (30.1 vs. 10.4%; rate ratio 2.91 95% CI 2.16-3.91). Only one of 31 (3.2%) children who underwent CT in the ED had an ICH. This patient rapidly deteriorated in the ED on arrival and required neurosurgery. None of the patients with bleeding disorders who did not have a CT obtained in the ED or had an initial negative CT had evidence of ICH on follow up. CONCLUSIONS: Although children with a bleeding disorder and a head trauma more often received a CT scan in the ED, their risk of ICH seemed low and appeared associated with post-traumatic clinical findings. Selective CT use combined with observation may be cautiously considered in these children based on clinical presentation and severity of bleeding disorder.