Evolution of Cardiovascular Findings in Multisystem Inflammatory Syndrome in Children (MIS-C) Across COVID-19 Variants: Common Trends and Unusual Presentations.

Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following COVID-19 infection. Cardiac involvement is common and includes left ventricular systolic dysfunction, cardiac marker elevation, electrocardiogram (ECG) changes, and coronary artery dilation. This single-center retrospective cohort study compares cardiovascular disease between three major SARS-CoV-2 variants and describes the evolution of findings in medium-term follow-up.

How I treat pediatric venous thromboembolism in the DOAC era.

The direct oral anticoagulants (DOACs) rivaroxaban and dabigatran are newly licensed for the treatment and prevention of venous thromboembolism (VTE) in children and mark a renaissance in pediatric anticoagulation management. They provide a convenient option over standard-of-care anticoagulants (heparins, fondaparinux, and vitamin K antagonists) because of their oral route of administration, child-friendly formulations, and significant reduction in monitoring. However, limitations related to therapeutic monitoring when needed and the lack of approved reversal agents for DOACs in children raise some safety concerns.

Thromboprophylaxis for children hospitalized with COVID-19 and MIS-C.

Background: Limited data exist about effective regimens for pharmacological thromboprophylaxis in children with acute coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C).

Objectives: Study the outcomes of institutional thromboprophylaxis protocol for primary venous thromboembolism (VTE) prevention in children hospitalized with acute COVID-19/MIS-C.

Methods: This single-center retrospective cohort study included consecutive children (aged less than 21 years) with COVID-19/MIS-C who received tailored intensity thromboprophylaxis, primarily with low-molecular-weight heparin, from April 2020 through October 2021.

DNase 1 Protects From Increased Thrombin Generation and Venous Thrombosis During Aging: Cross-Sectional Study in Mice and Humans.

Background Human aging is associated with increased risk of thrombosis, but the mechanisms are poorly defined. We hypothesized that aging induces peroxide-dependent release of neutrophil extracellular traps that contribute to thrombin generation and thrombosis. Methods and Results We studied C57BL6J mice and littermates of glutathione peroxidase-1 transgenic and wild-type mice at young (4 month) and old (20 month) ages and a healthy cohort of young (18-39 years) or middle-aged/older (50-72 years) humans.

Thrombotic potential during pediatric acute lymphoblastic leukemia induction: Role of cell-free DNA.

Background: Thromboembolism affects up to 30% of children undergoing treatment for acute lymphoblastic leukemia (ALL). Increased thrombin generation has been reported in ALL, but the mechanisms remain elusive.

Objective: We aimed to show that extracellular traps and cell-free DNA (cfDNA) promote thrombin generation in pediatric ALL.

How we approach thrombosis risk in children with COVID-19 infection and MIS-C.

Thrombosis within the microvasculature and medium to large vessels is a serious and common complication among critically ill individuals with coronavirus disease 2019 (COVID-19). While children are markedly less likely to develop severe disease than adults, they remain at risk for thrombosis during acute infection and with the post-acute inflammatory illness termed multisystem inflammatory syndrome in children. Significant knowledge deficits in understanding COVID-19-associated coagulopathy and thrombotic risk pose clinical challenges for pediatric providers who must incorporate expert opinion and personal experience to manage individual patients.

Up-front Treatment With Romiplostim in Children With Acquired Bone Marrow Failure: A Single Institutional Pediatric Case Series.

Background: Thrombopoietin receptor agonists are emerging as a therapeutic option for patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS). We report our experience of treating children with AA/MDS with romiplostim, thrombopoietin receptor agonist.

Observations: Three children (AA, 2; MDS, 1) received romiplostim treatment at a median dose of 10 μg/kg/week (starting dose: 5 μg/kg/wk; 2.

Epidemiology and outcomes of clinically unsuspected venous thromboembolism in children: A systematic review.

Background: Clinically unsuspected venous thromboembolic events (uVTE) detected during routine imaging pose a management challenge due to limited knowledge about their clinical significance. Unsuspected VTE are often referred as "asymptomatic," "incidental," or "clinically silent/occult" VTE.

Objective: To understand the epidemiology, management, and outcomes of uVTE in children.

Impact of the Survey of Inhibitors in Plasma-Product Exposed Toddlers (SIPPET) study and its post hoc analyses on clinical practice in the United States: A survey of Haemophilia and Thrombosis Research Society members.

Introduction: A recent randomized trial, the Survey of Inhibitors in Plasma-Product Exposed Toddlers (SIPPET), confirmed that exposure to recombinant FVIII (rFVIII) products doubled the risk of inhibitor development compared to plasma-derived FVIII (pdFVIII) in previously untreated (or minimally treated) patients (PUPs) with severe haemophilia A. SIPPET post hoc analyses showed that early exposure to rFVIII was more immunogenic and that rFVIII could harm low-risk PUPs with non-null mutations. Clinical implications of SIPPET findings for the haemophilia community were unclear.

Nox2 NADPH oxidase is dispensable for platelet activation or arterial thrombosis in mice.

Deficiency of the Nox2 (gp91phox) catalytic subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a genetic cause of X-linked chronic granulomatous disease, a condition in which patients are prone to infection resulting from the loss of oxidant production by neutrophils. Some studies have suggested a role for superoxide derived from Nox2 NADPH oxidase in platelet activation and thrombosis, but data are conflicting. Using a rigorous and comprehensive approach, we tested the hypothesis that genetic deficiency of Nox2 attenuates platelet activation and arterial thrombosis.

Successful medical management of a neonate with spontaneous splenic rupture and severe hemophilia A.

Splenic rupture in neonates is a rare event, usually occurring in the setting of underlying predisposing conditions. Here, we present the case of a term neonate who presented with worsening anemia in the setting of known hemolytic disease during the newborn period and was later found to have a spontaneous splenic rupture. He was subsequently diagnosed with severe hemophilia A, and was managed medically with recombinant factor VIII replacement therapy without any surgical intervention.

Current Practice of Pharmacological Thromboprophylaxis for Prevention of Venous Thromboembolism in Hospitalized Children: A Survey of Pediatric Hemostasis and Thrombosis Experts in North America.

Pharmacological thromboprophylaxis (pTP) is the most effective intervention to prevent venous thromboembolism (VTE) in hospitalized adults. High-quality studies investigating the role of pTP in children are lacking. The aim of this study is to understand pediatric hematologists' current practices of pTP prescription and to explore their opinion about universal adoption of pTP for high-risk hospitalized children.

Neonatal Compartment Syndrome Associated With Disseminated Intravascular Coagulation.

Neonatal compartment syndrome is a rare, but devastating limb-threatening condition that requires early recognition and timely surgical intervention. We discuss the clinical presentation and management challenges of a neonate with forearm compartment syndrome and disseminated intravascular coagulation.

Linkage analysis identifies a locus for plasma von Willebrand factor undetected by genome-wide association.

The plasma glycoprotein von Willebrand factor (VWF) exhibits fivefold antigen level variation across the normal human population determined by both genetic and environmental factors. Low levels of VWF are associated with bleeding and elevated levels with increased risk for thrombosis, myocardial infarction, and stroke. To identify additional genetic determinants of VWF antigen levels and to minimize the impact of age and illness-related environmental factors, we performed genome-wide association analysis in two young and healthy cohorts (n = 1,152 and n = 2,310) and identified signals at ABO (P < 7.

Primary Raynaud's phenomenon in an infant: a case report and review of literature.

Raynaud's phenomenon (RP) is an extremely unusual finding in early infancy. In the present report we describe a one-month-old previously healthy male infant who presented with unilateral acrocyanosis. Although infantile acrocyanosis is known to be a benign and self-resolving condition, it is generally bilateral and symmetric.

Clinical advances in hemophilia management.

Hemophilia is an excellent example in medicine where clinical translation of basic science discoveries has transformed the gloomy outlook of the disease. This review provides an overview of clinical advances in hemophilia management with a specific focus on the molecular heterogeneity of the disease and progress in management of patients with inhibitors. Novel therapeutics and the emerging ethical issues in the field of hemophilia are also discussed.

Proximal radio-ulnar synostosis with bone marrow failure syndrome in an infant without a HOXA11 mutation.

This report summarizes the clinical management of an infant with a proximal radio-ulnar synostosis and inherited bone marrow failure syndrome (PRUS/IBMFS). Molecular studies were negative for the characteristic HOXA11 mutation described earlier. He was successfully treated with a non-myeloablative hematopoietic stem cell transplantation from an human leukocyte antigen-identical sibling donor at the age of 3 months.

Management of neonatal aortic arch thrombosis with low-molecular weight heparin: a case series.

Aortic arch thrombosis (AAT) is a potentially life threatening condition in neonates. We report 3 neonates with AAT and complete occlusion of a unilateral internal carotid artery with multiple cerebral infarcts. Multidisciplinary input led to deferral of thrombolytic therapy and surgical thrombectomy owing to the potential risk of hemorrhage within the infarcts.

Current practice perspectives on the management of thrombosis in children with renal insufficiency: the results of a survey of pediatric hematologists in North America.

Background: No guidelines exist for the management of venous thromboembolic events (VTE) in children with renal insufficiency (RI).

Objective: To define current practice patterns of VTE management in children with RI.

Methods: An online multiple choice survey encompassing general questions/clinical scenarios related to thrombosis in RI.

Post-thrombotic syndrome in children: a single center experience.

Background: Development of post-thrombotic syndrome (PTS) is increasingly being recognized as a complication of deep venous thrombosis (DVT) in children.

Objective: To determine the prevalence, clinical characteristics, and predictors of moderate to severe PTS in children.

Methods: A retrospective chart review was performed on those children who were followed in the coagulation clinic for objectively confirmed DVTs from December 2004 to December 2006.