Causes of platelet loss during extracorporeal life support.

BACKGROUND: Most pediatric patients show a decline in platelet counts while on extracorporeal life support (ECLS) and require multiple platelet transfusions. To better understand platelet loss during ECLS, this study estimated platelet loss rates due to diagnostic phlebotomy, platelet activation, bleeding and other causes. METHODS: We collected data on 91 patients (1d-20y, 50 M, 41F). Platelet losses were estimated based on changes in platelet count, patient+circuit blood volume, and transfused platelet volumes. Platelet extracellular vesicles were measured by flow cytometry. RESULTS: Median platelet loss was 2.8 × 109 /L/hr, more than twice the normal rate of platelet removal and equivalent to a 67 000/µl decrease in platelet count per day. While platelet loss was correlated with platelet transfusion (r2  = 0.51), transfusion underestimated platelet loss in patients with large decreases in platelet count and over-estimated platelet loss in neonates where the circuit volume > patient blood volume. Patients with disseminated intravascular coagulation before or significant bleeding during ECLS have double the rate of platelet loss. Platelet activation accounted for ~32% of total platelet loss, bleeding ~36% and phlebotomy 4%, with the remaining one-third due to other causes. Annexin-negative platelet extracellular vesicle release, a measure of platelet damage, was increased 9-fold during ECLS. CONCLUSION: Our study is the first to quantitate total, phlebotomy and activation related platelet loss during ECLS. Platelet activation accounts for ~32% of total platelet loss, while bleeding doubles the platelet loss rate. The etiology of the remaining platelet loss is unknown.

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.

Line Associated Thrombosis in Pediatric Patients With NF-κB Pathway Variants.

Our report explores the complex role that nuclear factor-kappa B (NF-κB) plays in thrombosis formation, inflammation, and immunity; while additionally demonstrating that patients with NF-κB pathway pathogenic variants appear to carry a substantial thrombotic risk, particularly when secondary thrombotic risk factors are present. We propose that prophylactic anticoagulation should be strongly considered in such patients during high-risk situations and provide additional hematologic management strategies for those with NF-κB pathway alterations. We hope our work also calls to attention the potential need for a broader assessment of venous thromboembolism risk in patients with immune dysregulation to better delineate which patient populations may benefit from anticoagulation prophylaxis.

Risk factors for hospital-associated venous thromboembolism in critically ill children following cardiothoracic surgery or therapeutic cardiac catheterisation.

BACKGROUND: Paediatric hospital-associated venous thromboembolism is a leading quality and safety concern at children's hospitals. OBJECTIVE: The aim of this study was to determine risk factors for hospital-associated venous thromboembolism in critically ill children following cardiothoracic surgery or therapeutic cardiac catheterisation. METHODS: We conducted a retrospective, case-control study of children admitted to the cardiovascular intensive care unit at Johns Hopkins All Children's Hospital (St. Petersburg, Florida, United States of America) from 2006 to 2013. Hospital-associated venous thromboembolism cases were identified based on ICD-9 discharge codes and validated using radiological record review. We randomly selected two contemporaneous cardiovascular intensive care unit controls without hospital-associated venous thromboembolism for each hospital-associated venous thromboembolism case, and limited the study population to patients who had undergone cardiothoracic surgery or therapeutic cardiac catheterisation. Odds ratios and 95% confidence intervals for associations between putative risk factors and hospital-associated venous thromboembolism were determined using univariate and multivariate logistic regression. RESULTS: Among 2718 admissions to the cardiovascular intensive care unit during the study period, 65 met the criteria for hospital-associated venous thromboembolism (occurrence rate, 2%). Restriction to cases and controls having undergone the procedures of interest yielded a final study population of 57 hospital-associated venous thromboembolism cases and 76 controls. In a multiple logistic regression model, major infection (odds ratio=5.77, 95% confidence interval=1.06-31.4), age ⩽1 year (odds ratio=6.75, 95% confidence interval=1.13-160), and central venous catheterisation (odds ratio=7.36, 95% confidence interval=1.13-47.8) were found to be statistically significant independent risk factors for hospital-associated venous thromboembolism in these children. Patients with all three factors had a markedly increased post-test probability of having hospital-associated venous thromboembolism. CONCLUSION: Major infection, infancy, and central venous catheterisation are independent risk factors for hospital-associated venous thromboembolism in critically ill children following cardiothoracic surgery or cardiac catheter-based intervention, which, in combination, define a high-risk group for hospital-associated venous thromboembolism.

Development of a new risk score for hospital-associated venous thromboembolism in noncritically ill children: findings from a large single-institutional case-control study.

OBJECTIVE: To determine risk factors for pediatric hospital-associated venous thromboembolism (HA-VTE) in noncritically ill children to derive a novel HA-VTE risk model for this population. STUDY DESIGN: Patients with HA-VTE were identified retrospectively via the electronic health record at All Children's Hospital Johns Hopkins Medicine from April 10, 2013 through January 1, 2006. Seven contemporaneous, noncritically ill control children were randomly selected for each case of HA-VTE. The association between putative risk factors and HA-VTE was estimated with ORs and 95% CIs, which were calculated using the Wald method. A P-value threshold ≤.2 was used in univariate analysis for inclusion into a multivariate (adjusted) model. RESULTS: Fifty cases of HA-VTE occurred in noncritically ill children. The presence of a central venous catheter (OR 27.67, 95% CI, 8.40-91.22), infection (OR 10.40, 95% CI, 3.46-31.25), and length of stay ≥4 days (OR 5.26, 95% CI, 1.74-15.88) were found to be statistically significant risk factors for HA-VTE. An 8-point risk score was derived in which scores of 8 points, 7 points, and ≤6 points corresponded to venous thromboembolism risks of 12.5%, 1.1%, and 0.1%, respectively. CONCLUSION: The presence of a central venous catheter, infection, and length of stay ≥4 days are significant risk factors for HA-VTE in noncritically ill children, forming the basis for a new risk score that could inform venous thromboembolism prophylaxis decision-making. These findings warrant prospective validation.

Clinical Reasoning: A 17-Year-Old Adolescent Boy With New Altered Mental Status in the Pediatric Intensive Care Unit.

We present the case of a 17-year-old adolescent boy admitted to the Pediatric Intensive Care Unit with an extensive necrotizing soft tissue infection who subsequently developed altered mental status and autonomic instability. Altered mental status is a common occurrence in critically ill children with a broad differential of etiologies. After ruling out organic causes of encephalopathy, management is typically focused on avoiding deliriogenic agents, including benzodiazepines. Dopamine antagonist medications may also be administered adjunctively to manage agitation or delirium that is refractory to other measures. We review the workup and differential diagnosis for altered mentation in critically ill children and discuss the current understanding of a rare etiology of altered mental status in the pediatric population.

Molecular profiling and targeted therapy in pediatric gliomas: review and consensus recommendations.

As the field of neuro-oncology makes headway in uncovering the key oncogenic drivers in pediatric glioma, the role of precision diagnostics and therapies continues to rapidly evolve with important implications for the standard of care for clinical management of these patients. Four studies at major academic centers were published in the last year outlining the clinically integrated molecular profiling and targeting of pediatric brain tumors; all 4 demonstrated the feasibility and utility of incorporating sequencing into the care of children with brain tumors, in particular for children and young adults with glioma. Based on synthesis of the data from these studies and others, we provide consensus recommendations for the integration of precision diagnostics and therapeutics into the practice of pediatric neuro-oncology. Our primary consensus recommendation is that next-generation sequencing should be routinely included in the workup of most pediatric gliomas.

Development of a new risk score for hospital-associated venous thromboembolism in critically-ill children not undergoing cardiothoracic surgery.

BACKGROUND: Although risk of hospital-associated venous thromboembolism (HA-VTE) differs between critically and non-critically ill children, studies to date have not led to distinct, pragmatic risk scores. OBJECTIVE: To determine risk factors for HA-VTE in critically ill children not undergoing cardiothoracic surgery, in order to derive a novel HA-VTE risk score for this population. METHODS: We conducted a retrospective analysis from January 2006 through April 2013 at All Children's Hospital Johns Hopkins Medicine. HA-VTE cases were identified using ICD-9 discharge diagnosis codes, with subsequent validation via radiologic record review. Cases were restricted to Pediatric Intensive Care Unit (PICU) admissions. Patients who underwent cardiothoracic surgery were excluded; cardiac catheterization per se was not exclusionary. For each case, three non-HA-VTE PICU controls were randomly selected. Data were abstracted on putative risk factors, and associations between risk factors and HA-VTE were estimated using odds ratios (ORs) and 95% confidence intervals (95%CIs). RESULTS: There were 57 HA-VTE cases and 171 controls. HA-VTE occurrence was 3 per 1000 PICU admissions (0.3%). Central venous catheter (CVC) (OR:26.64; 95%CI:7.46-95.13), length of stay (LOS) ≥4days (OR:20.22; 95%CI:2.27-180.07), and significant infection (OR:3.41; 95%CI:1.13-10.29) were independent, statistically-significant risk factors for HA-VTE in a multivariate model. A risk score was derived in which HA-VTE risk exceeded 2% (threshold for anticoagulant thromboprophylaxis in hospitalized adults) with a score of 15, and was >1% but <2% (risk zone for mechanical thromboprophylaxis in hospitalized adults) with scores of 7-14. CONCLUSION: The presence of a CVC, LOS≥4days and infection are significant risk factors for HA-VTE in critically ill children not undergoing cardiothoracic surgery, forming the basis for a new risk score that warrants prospective validation.

Risk factors for hospital-sssociated venous thromboembolism in the neonatal intensive care unit.

OBJECTIVE: To determine hospital-associated venous thromboembolism (HA-VTE) risk factors in critically ill neonates. METHODS: We conducted a case-control study in the neonatal intensive care unit (NICU) of All Children's Hospital Johns Hopkins Medicine (St. Petersburg, FL), from January 1, 2006 - April 10, 2013. We identified HA-VTE cases using electronic health record. Four NICU controls were randomly selected for each HA-VTE case. Associations between putative risk factors and HA-VTE were estimated using odds ratios (ORs) and ninety-five percent confidence intervals (95%CIs) from univariate and multivariate regression analyses. RESULTS: Twenty-three HA-VTE cases and 92 controls were included. The annual HA-VTE incidence was approximately 1.4 HA-VTE cases per 1,000 NICU admissions. In univariate analyses, mechanical ventilation (OR=7.27, 95%CI=2.02-26.17, P=0.002), central venous catheter (CVC; OR=52.95, 95%CI=6.80-412.71, P<0.001), infection (OR=7.24, 95%CI=2.66-19.72, P<0.001), major surgery (OR=5.60, 95%CI=1.82-17.22, P=0.003) and length of stay ≥15days (OR=6.67, 95%CI=1.85-23.99, P=0.004) were associated with HA-VTE. Only CVC (OR=29.04, 95%CI=3.18-265.26, P=0.003) remained an independent risk factor in the multivariate analysis. Based on this result, the estimated risk of HA-VTE in NICU patients with a CVC was 0.9%. CONCLUSION: This study identifies CVC as an independent risk factor for HA-VTE in critically ill neonates. However, the level of risk associated with CVC is below the conventional threshold for primary anticoagulation thromboprophylaxis. Larger studies are needed to substantiate these findings and identify novel putative risk factors to further distinguish NICU patients at highest HA-VTE risk.