Immunothrombosis and plasma fibrinolytic function for pediatric COVID-19: a secondary analysis from the COVAC-TP trial.

The relationship between fibrinolysis, inflammation, and prothrombotic risk among children hospitalized for coronavirus disease 2019 (COVID-19)-related illness is ill defined. To investigate the association between plasma fibrinolytic capacity and proinflammatory cytokine concentrations among children hospitalized for primary COVID-19 infection and multisystem inflammatory syndrome in children (MIS-C), we hypothesized that cytokine concentrations differ by clinical phenotype and are associated with hypofibrinolysis. We analyzed banked plasma specimens serially collected from children aged <18 years admitted for primary COVID-19 or MIS-C and enrolled in the COVID-19 Anticoagulation in Children-Thromboprophylaxis multicenter trial, an open-label, multicenter, phase 2 clinical trial conducted between July 2020 and May 2021.

How I Treat Pediatric Pulmonary Embolism.

Venous thromboembolism (VTE) affects approximately 1 in 200 hospitalized children. The diagnosis of pulmonary embolism (PE), the most severe clinical presentation of VTE, has increased dramatically by ~200% over the past two decades, disproportionately affecting adolescents, and is associated with adverse long-term post-PE sequelae. Nevertheless, the management of pediatric PE remains highly variable.

Thromboprophylaxis for Critically Ill Adolescents: A Multicenter Case-Control Study From the Children's Healthcare Advancements in Thrombosis Consortium.

Objectives: To determine if thromboprophylaxis, including pharmacologic, mechanical, or in combination, is associated with a hospital-acquired venous thromboembolism (HA-VTE) risk reduction among critically ill adolescents.

Design: Multicenter case-control study from the Children's Healthcare Advancements in Thrombosis Consortium Registry and VTE risk-model validation study from January 2012 to July 2022.

Setting: Thirty-two North American PICUs.

Diabetic Ketoacidosis and Venous Thromboembolism: A North American Virtual Pediatric Systems Registry Study, 2014-2023.

Objectives: To estimate the occurrence rate of venous thromboembolism (VTE) among critically ill children and young adults with diabetic ketoacidosis (DKA) and evaluate putative prothrombotic risk factors using a multicenter data registry.

Design: Multicenter, observational, retrospective study utilizing a cohort derived from the Virtual Pediatric Systems database from October 1, 2014, to December 31, 2023.

Setting: One hundred thirty-nine North American PICUs.

The Functional Characterization of Venous Thromboembolic Disease (FUVID) study: rationale, design, and methods of a prospective, observational, multicenter study to evaluate mechanisms of exercise intolerance and dyspnea following pediatric pulmonary embolism.

Background: To date, the focus of investigation in pediatric pulmonary embolism (PE) has been on PE recurrence and anticoagulant-related bleeding. While highly relevant, these outcomes do not fully capture functional limitations and the psychological impact that comprises post-PE syndrome.

Objectives: The primary objective of the Functional Characterization of Venous Thromboembolic Disease (FUVID) study was to investigate mechanisms of post-PE syndrome in children.

Anticoagulants in Children with Renal Impairment: A Narrative Review.

Venous thromboembolism is a common cause of morbidity and mortality in children with renal disease. To properly treat and prevent thromboembolism in this patient population, it is important to be familiar with the multitude of anticoagulant agents currently available. Many anticoagulant drugs undergo some extent of renal elimination.

Risks of incident venous thromboembolism, recurrent thromboembolism, and use of antithrombotic therapies among children with congenital heart disease undergoing cardiac surgery: a global multicenter analysis of real-world data.

Background: Data on the characteristics and antithrombotic treatments of venous thromboembolism (VTE) among children with congenital heart disease undergoing cardiac surgery are limited.

Objectives: We aimed to evaluate the features and rates of recurrent thromboembolism in real-world experience using a global multicenter dataset.

Methods: We queried the TriNetX global electronic health record-derived real-world data research platform for patients <18 years of age who underwent cardiac surgery for congenital heart disease with a diagnosis of VTE within 1 year of surgery.

Arterial thromboembolism, antithrombotic therapy, and risk of recurrent thromboembolism in children with CHD undergoing cardiac surgery.

Introduction: Data on arterial thromboembolism in children undergoing cardiac surgery are limited. We sought to characterise, and estimate rates of, incident and recurrent arterial thromboembolism, and describe antithrombotic therapies for treatment in a large multinational population of children with CHD undergoing cardiac surgery.

Methods: We queried the TriNetX global electronic health record (derived real-world data research platform) from 2017 to 2024 for patients less than 18 years of age and an index arterial thromboembolism within 1 year of congenital cardiac surgery.

How I approach pharmacological thromboprophylaxis in children.

The incidence of venous thromboembolism in children continues to rise, with the most recent analysis from the Pediatric Hospital Information Systems database in the United States reporting a 200-fold increase in pediatric hospitalization-related venous thromboembolism diagnoses over the past 2 decades. In the past decade, several pediatric venous thromboembolism risk prediction models have been published, in some cases derived from multi-institutional data, and multicenter randomized clinical trials of thromboembolism prevention in specific pediatric subpopulations have been conducted. Yet, apart from children hospitalized for COVID-19, guidelines for thromboprophylaxis (TP) in children that address several distinct at-risk subpopulations and settings for venous thromboembolism are presently lacking.

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.

Results of a multinational survey on the diagnostic and management practices of catheter-related arterial thrombosis in children and neonates: communication from the ISTH SSC Subcommittee on Pediatric and Neonatal Thrombosis and Hemostasis.

Background: Arterial thrombosis is increasingly recognized in children and is most commonly related to the presence of an arterial catheter. Diagnosis and treatment of arterial thrombosis in children varies widely and consists of commonly available anticoagulants and antiplatelet drugs. No evidence-based guidelines exist for management strategies for catheter-related arterial thrombosis (CAT).

Hospital-acquired venous thromboembolism among critically ill children with diabetic ketoacidosis: a multicenter, retrospective cohort study.

Background: Critically ill children and young adults with diabetic ketoacidosis are thought to be in a prothrombotic state. However, the rate of hospital-acquired venous thromboembolism and associated risk factors in this population have not been identified.

Objectives: Children hospitalized for diabetic ketoacidosis (DKA) may be at increased risk of hospital-acquired venous thromboembolism (HA-VTE).

Duration of anticoagulation for venous thromboembolism in pediatric patients: Evaluation of the Duration of Therapy for Thrombosis in Children (Kids-DOTT) trial outcomes at 2 years.

Background: The Multicenter Evaluation of the Duration of Therapy for Thrombosis in Children multinational, randomized clinical trial revealed noninferiority of a 6-week vs 3-month duration of anticoagulation for the treatment of provoked venous thromboembolism (VTE) in patients <21 years old in regard to net clinical benefit at 1 year.

Objectives: To evaluate noninferiority at 2 years.

Methods: Patients whose repeat imaging 6 weeks after VTE diagnosis did not show complete veno-occlusion were randomized to discontinue anticoagulation vs receive a total 3-month course and followed for 2 years for the occurrence of symptomatic recurrent VTE (efficacy outcome) and clinically relevant bleeding (safety outcome).

Frequency, characteristics, antithrombotic therapies, and outcomes of thromboembolism in paediatric patients with CHD undergoing cardiac surgery: a single centre retrospective study.

Introduction: Thromboembolism is a complication in paediatric patients with CHD requiring cardiac surgery. Previous research has focused on post-operative thromboembolism. This study aimed to describe thromboembolism frequency before or after cardiac surgery in children with CHD.

Intravenous Direct Thrombin Inhibitors for Acute Venous Thromboembolism or Heparin-Induced Thrombocytopenia with Thrombosis in Children: A Systematic Review of the Literature.

Intravenous direct thrombin inhibitors (DTIs) are used for thromboembolic disorders. This systematic review aims to characterize intravenous DTI agents, dosing, monitoring strategies (or use), bleeding, and mortality, in pediatric patients with acute venous thromboembolism (VTE) or heparin-induced thrombocytopenia with thrombosis (HITT). MEDLINE, Embase, and Cochrane's CENTRAL were searched from inception through July 2023.

Impact of clinically unsuspected venous thrombotic events on CVC removal and survival in pediatric cancer patients: A population-based study from the Maritimes, Canada.

Venous thromboembolism (VTE) is a well-recognized complication in pediatric cancer patients. We aimed to determine the frequency of central venous catheter (CVC) removal and survival impact of children with cancer who develop VTE. After ethics approval, a retrospective population-based study of cancer patients less than 21 years between 2005 and 2020, in the Maritime Provinces Nova Scotia, New Brunswick, and Prince Edward Island was conducted.

Leveraging a global, federated, real-world data network to optimize investigator-initiated pediatric clinical trials: the TriNetX Pediatric Collaboratory Network.

Objective: Clinical research networks facilitate collaborative research, but data sharing remains a common barrier.

Materials And Methods: The TriNetX platform provides real-time access to electronic health record (EHR)-derived, anonymized data from 173 healthcare organizations (HCOs) and tools for queries and analysis. In 2022, 4 pediatric HCOs worked with TriNetX leadership to found the Pediatric Collaboratory Network (PCN), facilitated via a multi-institutional data-use agreement (DUA).

Mechanical Thromboprophylaxis and Hospital-Acquired Venous Thromboembolism Among Critically Ill Adolescents: A U.S. Pediatric Health Information Systems Registry Study, 2016-2023.

Objectives: To estimate the rate of mechanical thromboprophylaxis (mTP) prescription among critically ill adolescents using a multicenter administrative database and determine whether mTP prescription is inversely associated with hospital-acquired venous thromboembolism.

Design: Multicenter, observational, retrospective study of the Pediatric Health Information Systems (PHIS) Registry cohort, January 2016 to December 2023.

Setting: Thirty PICUs located within quaternary pediatric referral centers in the United States.

Methods, precision, and analytical sensitivity of a novel low-plasma-volume assay of fibrinolytic capacity utilizing the euglobulin fraction.

Introduction: Fibrinolysis is a critical aspect of the hemostatic system, with assessment of fibrinolytic potential being critical to predict bleeding and clotting risk. We describe the method for a novel low-plasma-volume assay of fibrinolytic capacity utilizing the euglobulin fraction (the "modified mini-euglobulin clot lysis assay [ECLA]"), its analytic sensitivity to alterations in key fibrinolytic substrates/regulators, and its initial applications in acute and convalescent disease cohorts.

Methods: The modified mini-ECLA requires 50 μL of plasma, a maximal read time of 3 h (with most results available within 60 min), and is entirely performed in a 96-well microplate.

Epidemiology of clinically unsuspected venous thromboembolism in children with cancer: A population-based study from Maritimes, Canada.

Inconsistencies in the definition of clinically unsuspected venous thromboembolism (VTE) in pediatric patients recently led to the recommendation of standardizing this terminology. Clinically unsuspected VTE (cuVTE) is defined as the presence of VTE on diagnostic imaging performed for indications unrelated to VTE in a patient without symptoms or clinical history of VTE. The prevalence of cuVTE in pediatric cancer patients is unclear.

Invasive Mechanical Ventilation and Risk of Hospital-Acquired Venous Thromboembolism.

Background: This study sought to estimate the overall cumulative incidence and odds of Hospital-acquired venous thromboembolism (VTE) among critically ill children with and without exposure to invasive ventilation. In doing so, we also aimed to describe the temporal relationship between invasive ventilation and hospital-acquired VTE development.

Methods: We performed a retrospective cohort study using Virtual Pediatric Systems (VPS) data from 142 North American pediatric ICUs among children < 18 y of age from January 1, 2016-December 31, 2022.