Efficacy, safety, and quality of life 4 years after valoctocogene roxaparvovec gene transfer for severe hemophilia A in the phase 3 GENEr8-1 trial.

Background: Valoctocogene roxaparvovec, an adeno-associated virus-mediated gene therapy for severe hemophilia A, enables endogenous factor (F)VIII expression and provides bleed protection.

Objectives: Determine valoctocogene roxaparvovec durability, efficacy, and safety 4 years after treatment.

Methods: In the phase 3 GENEr8-1 trial, 134 adult male persons with severe hemophilia A without inhibitors and previously using FVIII prophylaxis received a 6 × 10 vg/kg infusion of valoctocogene roxaparvovec.

International Society on Thrombosis and Haemostasis Clinical Practice Guideline for Treatment of Congenital Haemophilia-A Critical Appraisal.

Introduction: Evidence-based clinical practice guidelines drive optimal patient care and facilitate access to high-quality treatment. Creating guidelines for rare diseases such as haemophilia, where evidence does not often come from randomized controlled trials but from non-randomized and well-designed observational studies and real-world data, is challenging. The methodology used for assessing available evidence should consider this critical fact.

Design of an international, phase IV, open-label study of simoctocog alfa in women/girls with hemophilia A undergoing surgery (NuDIMENSION).

Background: Although hemophilia A mainly affects males, carriers (defined as females with hemophilia A, as well as symptomatic or asymptomatic hemophilia A carriers) are at risk of excessive bleeding, particularly during trauma or during surgical procedures. Clinical trials have focused on male patients with severe disease, and data for females are limited. Improved, evidence-based treatment guidelines for management of hemophilia A carriers are required.

Efficacy of emicizumab in patients with severe haemophilia A without factor VIII inhibitors in Germany: evaluation of real-life data documented by the smart medication eDiary.

Background: Systematically documented data on real-world use of emicizumab, a bispecific antibody factor (F)VIII mimetic, are still lacking in people with severe haemophilia A (PwSHA). Smart medication, a real-time, online platform, monitors treatment administration and outcomes for people with haemophilia A in Germany.

Objective: To evaluate annualised bleeding rates (ABRs) and annualised joint bleeding rates (AJBRs), using data documented in the smart medication eDiary, for PwSHA receiving emicizumab.

JTH in the Clinic: Deconstructing the ISTH Hemophilia Guidelines for the Clinician.

Recently, the ISTH Hemophilia Guidelines were published in this journal. The authors of these guidelines should be commended for a Herculean task that took years to complete, and while this is no doubt a welcome addition to the literature, it does leave many questions for the clinician. Primarily this is due to as 11 of the 13 recommendations being conditional essentially meaning "that clinicians and patients need to consider individual preferences as well as the specific circumstances in which the decision is being made for implementation of the recommendation.

A cluster of pediatric vaccine-induced immune thrombotic thrombocytopenia-like cases with thrombosis and thrombocytopenia following respiratory infections-case series.

Background: Adenoviral vector COVID-19 vaccine-induced immune thrombotic thrombocytopenia (VITT) is a heparin-independent platelet-activating disorder. An increasing number of VITT-like disorders without previous vaccination are being identified.

Key Clinical Question: To explore the association of the pediatric cluster of postinfectious thrombosis and thrombocytopenia with VITT-like disorders.

Explorations of strategies for inclusion for newly qualified physiotherapists from racially minoritised groups in a large, urban NHS Trust, UK.

Objectives: The study aimed to i) understand the experiences of newly qualified physiotherapists from racially minoritised backgrounds in a large hospital physiotherapy department and ii) co-create and implement inclusive strategies to affect work culture.

Design: The project used an action research design with co-creation principles and was in 3 phases. Phase 1 explored the experiences of inclusion for newly qualified racially minoritised staff, using focus groups and transcripts analysed thematically.

UKHCDO gene therapy taskforce: Guidance for implementation of haemophilia gene therapy into routine clinical practice for adults.

Introduction: 2022 was a landmark year with two adeno-associated viral vectors (AAVs) receiving conditional marketing authorization from EMA for the treatment of persons with severe haemophilia A and severe to moderately severe haemophilia B and a third in 2024. Gene therapy is a transformative, irreversible treatment with long-lasting effects, necessitating development of new clinical pathways to ensure optimal outcomes.

Aim: To develop a consensus framework and service specification for delivery of AAV gene therapy for haemophilia in adults within the UK using the hub-and-spoke model proposed by the European Association of Haemophilia and Allied Disorders and the European Haemophilia Consortium.

Concizumab prophylaxis in people with haemophilia A or haemophilia B without inhibitors (explorer8): a prospective, multicentre, open-label, randomised, phase 3a trial.

Background: Concizumab is an anti-tissue factor pathway inhibitor monoclonal antibody in development as a once-daily, subcutaneous prophylaxis for patients with haemophilia A or haemophilia B with or without inhibitors. We aimed to assess the efficacy and safety of concizumab in patients with haemophilia A or B without inhibitors. Here we report the results from the confirmatory analysis cutoff.

Laboratory and Molecular Diagnosis of Factor XI Deficiency.

The prevalence of factor XI (FXI) deficiency is 1 per 10 to 20,000 in the general population, much higher than that reported in most texts. The prevalence is higher in Ashkenazi Jews where it is about 1:20. Clinically, FXI deficiency presents as a mild bleeding disorder mostly associated with posttraumatic or postsurgical hemorrhages or unexplained minor bleeding.

Adherence and Quality of Life in Adult Patients With Haemophilia A, Haemophilia B and Von Willebrand Disease: A National Cross-Sectional Survey.

Background: New treatments for patients with bleeding disorders (PWB) have emerged, including products with extended half-life and subcutaneous administration. These less frequent treatments can potentially enhance quality of life (QoL), but adherence becomes critically important.

Aim: To investigate adherence and QoL among PWB and explore the correlation between treatment adherence and QoL in adult patients with haemophilia A (HA), haemophilia B (HB) and Von Willebrand disease (vWD) in Denmark.

MR Imaging of Hemosiderin Deposition in the Ankle Joints of Patients with Haemophilia: The Contribution of a Multi-Echo Gradient-Echo Sequence-Correlation with Osteochondral Changes and the Number and Chronicity of Joint Bleeds.

We aim (a) to introduce an easy-to-perform multi-echo gradient-echo sequence (mGRE) for the detection of hemosiderin deposition in the ankle joints of boys with haemophilia (b) to explore the associations between the presence and severity of hemosiderin deposition and the other components of haemophilic arthropathy, the clinical score, and the number and chronicity of joint bleeds. An MRI of 41 ankle joints of 21 haemophilic boys was performed on a 3 T MRI system using an mGRE sequence in addition to the conventional protocol. Conventional MRI and mGRE were separately and independently assessed by three readers, namely, two musculoskeletal radiologists and a general radiologist for joint hemosiderin.

The management of liver disease in people with congenital bleeding disorders: guidance from European Association for Haemophilia and Allied Disorders, European Haemophilia Consortium, ISTH, and World Federation of Hemophilia.

People with bleeding disorders (PWBD) have been exposed to the risk of developing chronic viral hepatitis and cirrhosis after replacement therapy. Today, the advent of new pharmacologic strategies for the control of hemostasis and the efficacious antiviral therapies against hepatitis C virus and hepatitis B virus have significantly reduced this risk. However, the definitive success for liver health in this clinical setting is also influenced by other factors, such as the severity of liver disease at the time of hepatitis B virus/hepatitis C virus antiviral therapy and the exposure to highly prevalent factors of chronic liver damage (eg, metabolic dysfunction and/or alcohol) that can cause a residual risk of complications such as hepatocellular carcinoma, portal hypertension, and liver insufficiency.

Real-world use of recombinant porcine sequence factor VIII in the treatment of acquired hemophilia A: EU PASS.

Background: Recombinant porcine factor VIII (rpFVIII; susoctocog alfa) is indicated for the treatment of bleeding events (BEs) in adults with acquired hemophilia A (AHA).

Objectives: To assess the safety, utilization, and effectiveness of rpFVIII in clinical practice.

Design: EU post-authorization safety study (PASS) (NCT03199794) was a multicenter, noninterventional, post-authorization safety study conducted in adults with AHA.

Pharmacokinetic model-based assessment of factor IX prophylaxis treatment regimens in severe hemophilia B.

An important aspect of improving care for people with hemophilia B (HB) is developing optimal treatment strategies. Here we aimed to provide in-silico evidence, comparing the estimated optimal posology of factor IX (FIX) products to support the patient-physician decision-making process. A population pharmacokinetic (popPK) model-based assessment comparing the performance of FIX products (rFIX, rIX-FP, rFIXFc, N9-GP) was developed.

Damoctocog Alfa Pegol, a PEGylated B-domain Deleted Recombinant Extended Half-life Factor VIII for the Treatment of Hemophilia A: A Product Review.

Damoctocog alfa pegol (BAY 94-9027, Jivi), is a site-specifically PEGylated, extended half-life recombinant factor VIII (FVIII) that is approved in several European and non-European countries for on-demand treatment and prophylaxis of bleeding in previously treated patients aged ≥ 12 years with hemophilia A. Reliable measurements can be obtained using most one-stage and chromogenic FVIII assays over a wide concentration range. The efficacy, safety and pharmacokinetics (PK) of damoctocog alfa pegol have been studied extensively in the PROTECT VIII clinical trials, and its long-term safety and effectiveness profile is continuing to build through observational and interventional real-world studies.