Systematic Analysis of the Design, Methodology and Patient Population Characteristics of the Pediatric Direct Oral Anticoagulant (DOAC) Trials of Venous Thromboembolism Treatment.

Introduction: 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.

Objective: 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: Systematic search of MEDLINE, EMBASE, the Cochrane Library and ClinicalTrials.

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.

Apixaban overdose in children: case report and proposed management. A brief communication from the Pediatric and Neonatal Thrombosis and Hemostasis SSC of ISTH.

Background: Direct oral anticoagulants are commonly prescribed for adults and increasingly also for children requiring anticoagulation therapy. While household medications should not be accessible to children, accidental, and intentional overdoses occur.

Key Clinical Question: How should apixaban overdose in children be managed?.

A post hoc analysis of PROTECT VIII kids assessing long-term efficacy and safety of damoctocog alfa pegol in adolescents with severe haemophilia A.

Introduction: The safety and efficacy of the extended half-life factor VIII (FVIII) product damoctocog alfa pegol (BAY 94-9027, Jivi®) has been demonstrated in the PROTECT VIII Kids study (NCT01775618), where male previously-treated patients (PTPs) aged <12 years old with severe haemophilia A and ≥ 50 exposure days (EDs) were treated prophylactically. The PROTECT VIII Kids extension study assessed the long-term safety and efficacy of damoctocog alfa pegol in the same population.

Aim: To evaluate the long-term impact of damoctocog alfa pegol in a post hoc subgroup analysis of adolescent patients in the PROTECT VIII Kids study and its extension from 12th birthday onwards.

Assessment of exposure to direct oral anticoagulants in elderly hospitalised patients.

It is unclear whether elderly patients established on direct oral anticoagulants (DOACs) have greater exposure to these drugs, which could subsequently increase their risk of bleeding. We assessed DOAC exposure and factors affecting it in a real-world elderly cohort of patients. For this, 151 medically stable hospital inpatients (76 established on apixaban, 61 on rivaroxaban, 14 on dabigatran) with a median [interquartile range (IQR)] age of 84 (78-89) years were recruited.

PROTECT VIII kids extension study: Long-term safety and efficacy of BAY 94-9027 (damoctocog alfa pegol) in children with severe haemophilia A.

Introduction: BAY 94-9027 (damoctocog alfa pegol; an extended half-life PEGylated recombinant factor VIII [FVIII]) demonstrated efficacy and safety in previously treated paediatric patients (PTPs) aged <12 years with severe haemophilia A in the PROTECT VIII Kids study (NCT01775618).

Aim: To evaluate the long-term safety of BAY 94-9027 in PTPs aged <12 years at enrolment.

Methods: In the PROTECT VIII Kids study, boys <12 years with severe haemophilia A were enrolled in two age cohorts (6-<12 years and <6 years) and treated prophylactically twice weekly, every 5 days or every 7 days, with BAY 94-9027 for ≥50 exposure days (EDs).

Pediatric May-Thurner Syndrome-Systematic review and individual patient data meta-analysis.

Background: The outcomes of deep vein thrombosis (DVT) in children with May-Thurner Syndrome (MTS) remain unclear.

Objectives: This systematic review and patient-level meta-analysis aims to describe the outcomes of children with MTS presenting with DVT.

Methods: A systematic review of the published literature was performed.

Safety and efficacy of rivaroxaban in pediatric cerebral venous thrombosis (EINSTEIN-Jr CVT).

Anticoagulant treatment of pediatric cerebral venous thrombosis has not been evaluated in randomized trials. We evaluated the safety and efficacy of rivaroxaban and standard anticoagulants in the predefined subgroup of children with cerebral venous thrombosis (CVT) who participated in the EINSTEIN-Jr trial. Children with CVT were randomized (2:1), after initial heparinization, to treatment with rivaroxaban or standard anticoagulants (continued on heparin or switched to vitamin K antagonist).

Consensus-based clinical recommendations and research priorities for anticoagulant thromboprophylaxis in children hospitalized for COVID-19-related illness.

Background: Observational studies indicate that children hospitalized with COVID-19-related illness, like adults, are at increased risk for venous thromboembolism (VTE). A multicenter phase 2 clinical trial of anticoagulant thromboprophylaxis in children hospitalized with COVID-19-related illness has recently been initiated in the United States. To date, there remains a paucity of high-quality evidence to inform clinical practice world-wide.

Elderly people are inherently sensitive to the pharmacological activity of rivaroxaban: implications for DOAC prescribing.

According to both trial and clinical data on direct oral anticoagulants (DOACs) elderly patients are at greatest risk of bleeding. It is unclear whether age intrinsically affects anticoagulation response. To investigate the age-related sensitivity to DOACs, we compared the pharmacological activity of the direct factor Xa inhibitor, rivaroxaban, between young and elderly subjects ex-vivo.

Therapeutic metamorphosis: Findings from a grounded theory study of the impact of low-dose prophylaxis in children living with haemophilia in India.

Introduction: The clinical benefits of administering low-dose prophylaxis in children with haemophilia are well established. Qualitative research describing the impact of prophylaxis on quality of life is comparatively rare in this area.

Aim: The aim of this study was to investigate in children the experiences of living and becoming adjusted to haemophilia before prophylaxis, by collecting information directly from children and their parents or guardians.

PROTECT VIII Kids: BAY 94-9027 (PEGylated Recombinant Factor VIII) safety and efficacy in previously treated children with severe haemophilia A.

Introduction: BAY 94-9027, a site-specifically PEGylated, B-domain-deleted recombinant factor VIII (FVIII) with extended half-life, demonstrated efficacy for bleed prevention and treatment in previously treated adolescents and adults with severe haemophilia A.

Aim: To assess BAY 94-9027 in children with severe haemophilia A.

Methods: In the two-part PROTECT VIII Kids study, boys <12 years with <1% FVIII and >50 exposure days (EDs) to FVIII were enrolled in two cohorts (<6 years; 6-<12 years) and treated with BAY 94-9027 prophylaxis twice-weekly, every 5 days, or every 7 days at physician discretion for ≥50 EDs (Part 1) or twice-weekly for 12-weeks (Part 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.

Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial.

Background: Treatment of venous thromboembolism in children is based on data obtained in adults with little direct documentation of its efficacy and safety in children. The aim of our study was to compare the efficacy and safety of rivaroxaban versus standard anticoagulants in children with venous thromboembolism.

Methods: In a multicentre, parallel-group, open-label, randomised study, children (aged 0-17 years) attending 107 paediatric hospitals in 28 countries with documented acute venous thromboembolism who had started heparinisation were assigned (2:1) to bodyweight-adjusted rivaroxaban (tablets or suspension) in a 20-mg equivalent dose or standard anticoagulants (heparin or switched to vitamin K antagonist).

Results of a multinational survey of diagnostic and management practices of thromboembolic pulmonary embolism in children.

Introduction: The incidence of thromboembolic (TE)-pediatric pulmonary embolism (PPE) is increasing. We sought to evaluate current practice patterns and gaps in the management of TE-PPE.

Materials And Methods: After Institutional Review Board approval, SurveyMonkey® questions were sent to members of the Pediatric/Neonatal Thrombosis and Hemostasis Subcommittee, of the International Society on Thrombosis and Haemostasis and the Hemostasis and Thrombosis Research Society.

Characterization and treatment of congenital thrombotic thrombocytopenic purpura.

Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare thrombomicroangiopathy caused by an inherited deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). There are limited data on genotype-phenotype correlation; there is no consensus on treatment. We reviewed the largest cohort of cTTP cases, diagnosed in the United Kingdom, over the past 15 years.