Adenovirus vectors can infect mouse megakaryocytes - implications for vaccine-induced thrombosis/thrombocytopenia.

Background: Adenoviruses, adenoviral vector vaccines, and gene delivery systems have been implicated in thrombosis/thrombocytopenia syndrome. The underlying cause remains unknown. We have previously hypothesized that infection of megakaryocytes (MKs), the progenitor cells of platelets, plays a central role in adenovirus- or adenoviral vector-induced thrombosis/thrombocytopenia.

Efficacy and Safety of Thrombolysis for Pediatric Venous Thromboembolism: A Systematic Review and Meta-analysis.

We conducted this systematic review to evaluate outcomes of thrombolysis followed by anticoagulation versus anticoagulation alone in pediatric patients with venous thromboembolism (VTE). This systematic review addresses mortality, VTE resolution, recurrence, bleeding, and organ-specific outcomes in five population, intervention, comparison, outcomes (PICO) questions on thrombolysis across pulmonary embolism (PE), extremity deep vein thrombosis (DVT), right atrial thrombosis (RAT), cerebral sinus venous thrombosis (CSVT), and renal vein thrombosis (RVT). Meta-analysis reported risk ratios or differences (95% confidence intervals), and absolute effects per 1,000 patients.

Characterization of Apixaban Pharmacokinetics/Pharmacodynamics and Dose Assessment in Pediatric Patients with Congenital or Acquired Heart Disease.

Apixaban is an oral direct inhibitor of factor Xa (FXa) that could be a treatment option for thromboembolism prevention in children with congenital or acquired heart disease (CAHD). Data from SAXOPHONE, a phase II pediatric study, were used to update a previously developed population pharmacokinetics (PPK) model and to assess the covariate effect of patient type on PK parameters while retaining previous covariates. Stochastic simulations were performed to assess whether the proposed dosing regimens in pediatric patients aged 28 days to < 18 years matched adult exposures.

Factors Influencing Long-Term Outcomes in Childhood Arterial Ischemic Stroke.

Background: Childhood arterial ischemic stroke (AIS) is associated with substantial long-term morbidity. This study aims to describe factors associated with recurrence, mortality, and neurological disability.

Methods: Australian children with radiologically confirmed AIS were enrolled prospectively to the Royal Children's Hospital stroke registry from 2003 to 2017.

Streptococcal Serology Reference Intervals in an Australian Pediatric Cohort.

Background: Diagnostic criteria for acute rheumatic fever and post-streptococcal glomerulonephritis, the 2 major autoimmune complications of Streptococcus pyogenes infection, include serological evidence of preceding infection. The S. pyogenes proteins, namely streptolysin O and deoxyribonuclease B, are the most widely used targets for clinical streptococcal serology.

American Society of Hematology/International Society on Thrombosis and Haemostasis 2024 updated guidelines for treatment of venous thromboembolism in pediatric patients.

Background: The American Society of Hematology (ASH) guidelines on treatment of pediatric venous thromboembolism (VTE) were published in 2018. In the last 6 years, there has been a 10-fold increase in the number of children involved in VTE treatment trials.

Objective: The ASH Committee on Quality and Guidelines agreed to update the pediatric guidelines in conjunction with the International Society on Thrombosis and Haemostasis (ISTH).

Untargeted proteomics enables ultra-rapid variant prioritisation in mitochondrial and other rare diseases.

Background: Only half of individuals with suspected rare diseases receive a genetic diagnosis following genomic testing. A genetic diagnosis allows access to appropriate care, restores reproductive confidence and reduces the number of potentially unnecessary interventions. A major barrier is the lack of disease agnostic functional tests suitable for implementation in routine diagnostics that can provide evidence supporting pathogenicity of novel variants, especially those refractory to RNA sequencing.

Continuous reference intervals for total serum immunoglobulin E in neonates and children.

Immunoglobulin E (IgE) is a group of antibodies involved with allergic sensitisation. Levels of total IgE change with age and tend to be higher in individuals with allergic diseases than in those without. To improve the clinical utility of total IgE, this study aimed to establish continuous paediatric reference intervals (RIs) for healthy individuals.

Extended-phase anticoagulant treatment of acute venous thromboembolism in children: a cohort study from the EINSTEIN-Jr phase 3 trial.

Background: Extended-phase anticoagulation of venous thromboembolism in children is not well documented nor systematically reported. Previously, we reported on recurrent venous thromboembolism and bleeding during acute-phase anticoagulation in EINSTEIN-Jr, a randomised controlled study in 500 children with venous thromboembolism comparing rivaroxaban to standard anticoagulants. The aim of the present study was to evaluate the efficacy and safety of extended-phase anticoagulant therapy in children and to characterise factors associated with the decision to extend anticoagulation.

A Novel Series of Synthetic Heparin-Mimetics-Itaconic Acid-Containing Copolymers for Targeting Tumor Cell Coagulability and Metastasis.

Thromboses are potentially fatal complication in malignant tumor diseases. Today, oral anticoagulants are considered equivalent alternatives to low molecular weight heparin (LMWH) in guideline-based treatments of cancer-associated thromboses. Nevertheless, debates on potential antitumorigenic heparin activities beyond anticoagulation are still highly relevant.

Hemostatic Outcome Definitions in Pediatric Extracorporeal Membrane Oxygenation: Challenges in Cohorts From Rotterdam (2019-2023) and Melbourne (2016-2022).

Objectives: To determine if a priori standardization of outcome hemostatic definitions alone was adequate to enable useful comparison between two cohorts of pediatric extracorporeal membrane oxygenation (ECMO) patients, managed according to local practice and protocol.

Design: Comparison of two separate prospective cohort studies performed at different centers with standardized outcome definitions agreed upon a priori.

Setting: General and cardiac PICUs at the Royal Children's Hospital (RCH) in Melbourne, Australia, and the Sophia Children's Hospital (SCH) in Rotterdam, The Netherlands.

Beyond platelet activation: dysregulated lipid metabolism in defining risk and pathophysiology of VITT.

Background: VITT has emerged as a rare but serious adverse event linked primarily to adenoviral vector COVID-19 vaccinations, such as ChAdOx1-S (Oxford/AstraZeneca) vaccination. The syndrome is characterized by thrombosis with thrombocytopenia, elevated D-dimer, and pathologic platelet factor 4 antibodies within 42 days of vaccination.

Objectives: Despite dysregulated lipid metabolism underpinning many thrombotic conditions, the role of lipid alterations in VITT remains unexplored.

Over-the-counter carrageenan-based sprays may interfere with PCR testing of nasopharyngeal swabs to detect SARS-CoV-2.

Carrageenan-containing nasal sprays, available over-the-counter (OTC), are often marketed as having anti-viral effects. Carrageenan belongs to the glycosaminoglycan family alongside heparin, and heparin is known to inhibit real-time quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal swabs used to detect SARS-CoV-2. As heparin and carrageenan share structural similarities, this work aimed to investigate the interferent effect of carrageenan on RT-qPCR for SARS-CoV-2 detection across 4 different diagnostic platforms.

Systematic analysis of the design, methodology, and patient population characteristics of the pediatric direct oral anticoagulant trials of venous thromboembolism treatment.

Background: The pediatric direct oral anticoagulation (DOAC) trials provide an opportunity to evaluate and characterize challenges in their design and execution to inform future antithrombotic trials.

Objectives: To perform a systematic review of pediatric DOAC trials for the treatment of venous thromboembolism to critically appraise their methodology and understand the feasibility and challenges.

Methods: We performed a systematic search of MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.

Continuous reference intervals for holotranscobalamin, homocysteine and folate in a healthy paediatric cohort.

Background: The detection of deficiencies in B and folate children is important. However, despite the availability of various markers to assess B and folate metabolism, there are limited studies describing the reference intervals (RIs) and changes during growth and development for these markers in healthy children.

Methods: Using samples collected from 378 children aged 30 days-< 18 years, we derived continuous RIs for holotranscobalamin, homocysteine and red cell folate.

Comprehensive Characterization of Surface-Bound Proteins and Measurement of Fibrin Fiber Thickness on Extracorporeal Membrane Oxygenation Circuits Collected From Patients.

Objective: To characterize surface-bound proteins and to measure the thickness of fibrin fibers bound to extracorporeal membrane oxygenation (ECMO) circuits used in children.

Design: Single-center observational prospective study, April to November 2021.

Setting: PICU, Royal Children's Hospital, Melbourne, Australia.

Anticoagulation Monitoring and Targets: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

Objectives: To derive systematic-review informed, modified Delphi consensus regarding anticoagulation monitoring assays and target levels in pediatric extracorporeal membrane oxygenation (ECMO) for the Pediatric ECMO Anticoagulation CollaborativE.

Data Sources: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021.

Study Selection: Anticoagulation monitoring of pediatric patients on ECMO.

Anticoagulant Medications: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

Objectives: To derive systematic-review informed, modified Delphi consensus regarding the medications used for anticoagulation for pediatric extracorporeal membrane oxygenation (ECMO) for the Pediatric ECMO Anticoagulation CollaborativE (PEACE).

Data Sources: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021.

Study Selection: Included studies assessed anticoagulation used in pediatric ECMO.

Executive Summary: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE (PEACE) Consensus Conference.

Objectives: To present recommendations and consensus statements with supporting literature for the clinical management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus conference.

Data Sources: Systematic review was performed using PubMed, Embase, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial meetings of international, interprofessional experts in the management ECMO for critically ill children.

Study Selection: The management of ECMO anticoagulation for critically ill children.

Immunofluorescence Protocol for Characterization of Platelet and Leukocyte Binding in Extracorporeal Membrane Oxygenation (ECMO) Circuits.

The continuous contact between blood and the foreign surface of the extracorporeal membrane oxygenation (ECMO) circuit contributes to hemostatic, inflammatory, and other physiological disturbances observed during ECMO. Although previous studies have extensively investigated blood samples from patients on ECMO, cell adsorption to the ECMO circuit as an additional factor that could potentially influence clinical outcomes, has largely been overlooked. Here we provide a detailed immunofluorescence (IF) protocol designed to characterize cellular binding on ECMO circuits collected from patients.

Antiviral Activities of Heparan Sulfate Mimetic RAFT Polymers Against Mosquito-borne Viruses.

Mosquito-borne viruses are a major worldwide health problem associated with high morbidity and mortality rates and significant impacts on national healthcare budgets. The development of antiviral drugs for both the treatment and prophylaxis of these diseases is thus of considerable importance. To address the need for therapeutics with antiviral activity, a library of heparan sulfate mimetic polymers was screened against dengue virus (DENV), Yellow fever virus (YFV), Zika virus (ZIKV), and Ross River virus (RRV).