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.

International Perspectives on Vitamin K Deficiency Bleeding in Infants: A Cross-Sectional Questionnaire-Based Survey.

Purpose: Vitamin K deficiency bleeding (VKDB) can occur in neonates and infants due to low placental transfer and storage of VK. Although the incidence has decreased with global VK prophylaxis at birth, VKDB remains a concern. This study aimed to assess the recent magnitude, risk factors, and outcomes of VKDB and barriers/limitations to VK prophylaxis.

A novel Computable phENotype To Identify Pulmonary Embolism in chilDrEn: The CENTIPEDE Study.

Background: Pediatric pulmonary embolism (PE) is rare and requires multicenter research to generate meaningful results and improve care. PEDSnet is a multicenter learning health system including 10 pediatric institutions and a valuable tool to study rare diseases.

Objectives: We aimed to develop a computable phenotype (CP) to accurately identify pediatric PE in PEDSnet.

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.

The eTHINK Study: Cognitive and Behavioral Outcomes in Children with Hemophilia.

Objective: To assess cognitive, behavioral, and adaptive functions in children and young adults with hemophilia treated according to contemporary standards of care.

Study Design: Evolving Treatment of Hemophilia's Impact on Neurodevelopment, Intelligence, and Other Cognitive Functions (eTHINK) is a US-based, prospective, cross-sectional, observational study (September 2018 through October 2019). Males (aged 1-21 years) with hemophilia A or B of any severity, with or without inhibitors, were eligible.

Real-world experience of direct oral anticoagulant use in a single pediatric center.

Background: Pediatric venous thromboembolism has increased by 130%-200%, specifically in hospitalized children, and direct oral anticoagulants (DOACs) offer several therapeutic advantages.

Methods: This study aims to evaluate the real-world epidemiological and outcome data from a retrospective review of pediatric patients treated with DOACs from January 1, 2013 to December 31, 2022. In this single-center, IRB-approved study, 65 patients were identified and analyzed using SPSS statistical software, and a descriptive statistical analysis was conducted.

Considerations for instituting pediatric pulmonary embolism response teams: A tool kit.

The incidence of pediatric pulmonary embolism (PE) has increased by 200 % in the last decade, but at a single center, it is still infrequent. Given the unique epidemiologic features of pediatric PE, diagnosis is often delayed, and the management is empiric, based on individual physician experience or preference. Thus, there is a strong need for center-specific uniform management of pediatric PE patients.

Balancing anticoagulation and hemostasis in an infant with severe hemophilia A during cardiac transplantation: Review of the literature and development of a surgical protocol.

Hemophilia A is a disorder resulting in a deficiency of clotting factor VIII that can lead to life-threatening bleeding. Evidence-based guidelines for surgical interventions like cardiac surgery are limited. Anticoagulation is necessary for cardiac bypass, thus risk of bleeding in a patient with hemophilia is increased and requires careful attention to maintain hemostasis.

Unusual Presentation of Thrombotic Thrombocytopenic Purpura in a Newly Diagnosed Pediatric Patient With Systemic Lupus Erythematosus in the Setting of MIS-C.

The understanding of coronavirus disease 2019 (COVID-19) immune dysregulation is evolving. Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with alternations in both innate and adaptive immunity, probably caused by a complex interplay of genetics and environmental exposure with various triggers. A rare hematological complication of SLE as well as recently reported in an adult with COVID-19 is thrombotic thrombocytopenic purpura.

Assessment of Arsenic Trioxide and All-trans Retinoic Acid for the Treatment of Pediatric Acute Promyelocytic Leukemia: A Report From the Children's Oncology Group AAML1331 Trial.

Importance: All-trans retinoic acid (ATRA) and arsenic trioxide therapy without the use of maintenance therapy has been found to be beneficial for the treatment of adults with standard-risk acute promyelocytic leukemia (APL). However, it is unclear whether similar regimens are safe and beneficial for the treatment of high-risk APL or pediatric patients with standard-risk APL.

Objective: To assess whether treatment with an ATRA and arsenic trioxide-based regimen is safe and allows for the elimination or substantial reduction of chemotherapy use among pediatric patients with standard-risk or high-risk APL, respectively.

Illustrated State-of-the-Art Capsules of the ISTH 2020 Congress.

This year's Congress of the International Society of Thrombosis and Haemostasis (ISTH) was hosted virtually from Philadelphia July 17-21, 2021. The conference, now held annually, highlighted cutting-edge advances in basic, population and clinical sciences of relevance to the Society. Despite being held virtually, the 2021 congress was of the same scope and quality as an annual meeting held in person.

Concomitant use of combined hormonal contraceptives and antifibrinolytic agents for the management of heavy menstrual bleeding: A practice pattern survey.

Introduction: Concomitant antifibrinolytic agents and combined hormonal contraceptives (CHC) have been anecdotally used to manage refractory heavy menstrual bleeding (HMB). Yet, there remains uncertainty among clinicians regarding the safety of this therapeutic option as concomitant CHC is listed as a contraindication to tranexamic acid use in the United States.

Aim: To describe current treatment practices and physician-reported safety and effectiveness of concomitant antifibrinolytics and CHCs.

Current challenges for men and women with mild-to-moderate haemophilia.

Current treatments in the field of haemophilia are changing the phenotype of many patients with severe haemophilia to that of mild haemophilia. Despite this improvement, those with mild-to-moderate haemophilia A and haemophilia B continue to experience unmet needs. Whereas some patients with mild-to-moderate haemophilia experience similar complications to those of patients with severe haemophilia, they possess several unique attributes.

ETV6 germline mutations cause HDAC3/NCOR2 mislocalization and upregulation of interferon response genes.

ETV6 is an ETS family transcription factor that plays a key role in hematopoiesis and megakaryocyte development. Our group and others have identified germline mutations in ETV6 resulting in autosomal dominant thrombocytopenia and predisposition to malignancy; however, molecular mechanisms defining the role of ETV6 in megakaryocyte development have not been well established. Using a combination of molecular, biochemical, and sequencing approaches in patient-derived PBMCs, we demonstrate abnormal cytoplasmic localization of ETV6 and the HDAC3/NCOR2 repressor complex that led to overexpression of HDAC3-regulated interferon response genes.

Bivalirudin during thrombolysis with catheter-directed tPA in a heparin-refractory patient: A case report.

Venous thromboembolism has increasing significance in hospitalized pediatric patients. Patients who have life-threatening or limb-threatening thrombotic events require thrombolysis in addition to anticoagulation. In patients who show signs of heparin resistance or heparin-induced thrombocytopenia, it is imperative to identify alternative therapeutic options.

Neuropsychological function in children with hemophilia: A review of the Hemophilia Growth and Development Study and introduction of the current eTHINK study.

Almost all of what is known about neurologic and cognitive development in hemophilia derives from the Hemophilia Growth and Development Study, conducted during an era when treatment regimens and comorbidities differed significantly from the current environment. Results suggested hemophilia and human immunodeficiency virus had independent effects, and hemophilia negatively impacts academic achievement, attention, and behavior. The introduction of prophylaxis treatment in hemophilia has created the need for re-evaluation of the effects of hemophilia on neurodevelopment and cognition.

Thrombotic events with recombinant activated factor VII (rFVIIa) in approved indications are rare and associated with older age, cardiovascular disease, and concomitant use of activated prothrombin complex concentrates (aPCC).

Purpose: Recombinant activated factor VII (rFVIIa; NovoSeven RT; Novo Nordisk A/S, Bagsvaerd, Denmark) is approved in the United States for the treatment of bleeding and perioperative management in congenital hemophilia with inhibitors (CHwI), acquired hemophilia (AH), congenital factor VII (FVII) deficiency, and Glanzmann's thrombasthenia (GT) with refractoriness to platelets. The aim of the current analysis was to review clinical trials and registries pre- and post-licensure for each indication to establish the estimated rate of thrombosis and then to establish the association of all reported thrombotic events (TEs) with certain risk factors listed for many years in the prescribing information (PI).

Patients And Methods: A retrospective safety assessment of both clinical trials and registries used to support licensure and postmarketing surveillance was performed.

Recombinant Von Willebrand factor concentrate in 2A Von Willebrand disease: comparison to plasma-derived Von Willebrand factor concentrate therapy.

: Type 2A sub-type of Von Willebrand disease (VWD) is characterized by the loss of high molecular weight multimers. Several plasma-derived Von Willebrand factor concentrates (PD-VWFC) are available for treatment and recently a recombinant VWF concentrate (rVWFC) has been approved for use in VWD for adults in the United States. We describe a patient with Type 2A VWD who had persistent refractory epistaxis despite treatment with PD-VWFC.

Continuous infusion of recombinant activated factor VII: a review of data in congenital hemophilia with inhibitors and congenital factor VII deficiency.

Introduction: Continuous infusion (CI) of clotting factors as a replacement therapy for perioperative hemostatic protection has been performed for many years, including with factors VIII and IX and recombinant activated factor VII (rFVIIa). This approach provides steady factor levels without requiring frequent administration of bolus doses.

Aim: To review safety, efficacy, and dosing data regarding CI of rFVIIa for hemostatic management of patients with congenital hemophilia with inhibitors (CHwI) or congenital factor VII deficiency (C7D).