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.

Superior Prophylactic Effectiveness of a Recombinant FVIIIFc Over Standard Half-Life FVIII in Hemophilia A: A-SURE Study.

Objectives: The 24-month, prospective, non-interventional, European multicenter A-SURE study evaluated the real-world effectiveness of prophylaxis using an extended half-life recombinant factor VIII (FVIII) Fc fusion protein, efmoroctocog alfa (hereinafter rFVIIIFc), compared with prophylaxis using standard half-life (SHL) FVIII products in patients with hemophilia A.

Methods: Primary endpoints were annualized bleeding rate (ABR), annualized injection frequency, and annualized factor consumption. A comparative study design unique for an observational hemophilia study was implemented to reduce potential confounding in effectiveness estimates, wherein each patient prescribed rFVIIIFc was matched with one receiving SHL FVIII.

Efficacy and safety of a recombinant von Willebrand factor treatment in acquired von Willebrand syndrome in case of bleeding and surgical procedures.

Introduction: Acquired von Willebrand syndrome (AVWS) is a rare haemorrhagic disorder. The prophylaxis and treatment of bleeding before surgery are complex. Since 2018, a new recombinant VWF (rVWF) concentrate that contains no factor VIII (FVIII) but a high amount of high molecular weight VWF multimers has been available in France.

Does the VWF:CB Assay Help to Diagnose von Willebrand Factor Deficiency in Patients With a Bleeding Disorder of Unknown Cause?

Introduction: The entity entitled bleeding disorder of unknown cause (BDUC) qualifies individuals displaying a mild haemorrhagic profile but normal routine coagulation tests. This study was designed to evaluate whether collagen-binding assay for von Willebrand Factor (VWF) measurement (VWF:CB) could allow to diagnose VW disease in such patients.

Methods: A large screening was conducted prospectively in two University Hospitals, using the bleeding assessment tool (BAT) recommended by the International Society of Thrombosis and Hemostasis.

Comparative evaluation of access to emicizumab (Hemlibra®) for people with haemophilia A in community and hospital pharmacies in France.

Since June 2021 in France, patients with haemophilia A with anti-factor VIII inhibitors and patients with severe haemophilia A without anti-factor VIII inhibitors have the choice between the community and the hospital pharmacy for dispensing emicizumab (Hemlibra®). This study aims to investigate patient-centred access to treatment by evaluating and comparing the dimensions of the Penchansky and Thomas model, between community and hospital pharmacies. The evaluation of access to treatment was based on the dimensions of the Penchansky and Thomas model: accessibility, availability, acceptability, accommodation and affordability.

Examining variability in the diagnosis and management of people with bleeding disorders of unknown cause: communication from the ISTH SSC Subcommittee on von Willebrand Factor.

Background: Bleeding disorder of unknown cause (BDUC) is characterized by a bleeding phenotype in the setting of normal hemostatic testing. No standardized diagnostic criteria or treatment algorithms exist for people with BDUC. To address the unmet need, the International Society on Thrombosis and Haemostasis von Willebrand Factor Scientific Subcommittee performed a real-world survey aimed at addressing knowledge gaps, developing consensus pathways, and ultimately improving care.

Haemophilic arthropathy: Diagnosis, management, and aging patient considerations.

Gene therapy and universal use of safer, more effective, and personalised prophylactic regimens (factor, and nonfactor) are expected to prevent joint bleeding and promote joint health in persons with haemophilia (PwH). Growing evidence suggests that subclinical bleeding, with active and inactive synovial proliferation, continues and haemophilic arthropathy remains a major morbidity in PwH despite early institution of joint prophylaxis. Joint health assessment is evolving with physical examination scores complementing imaging scores.

Mutational landscape, inhibitor development, and health-care burden in non-severe haemophilia A: A single-centre Australian experience.

Aim: To characterise non-severe haemophilia A (HA) patients enrolled on the Australian Bleeding Disorders Registry (ABDR) treated through a state-wide Haemophilia Treatment Centre (HTC) with respect to their mutational profile, inhibitor risk and health-care burden.

Method: We conducted a single-centre observational study of all non-severe HA patients treated at the Alfred Health HTC registered on the ABDR as of the 26th July 2023. Data were extracted from the ABDR and electronic medical record (EMR) regarding demographics, severity, genetic testing, treatment, inhibitors, bleeding events and procedures.

Management of severe factor XI deficiency in pregnancy: A case report.

Factor XI (FXI) deficiency is one of the rarest coagulation disorders with a frequency of 1:1,000,000. A 30-year-old woman, diagnosed with FXI deficiency at the age of 4, was admitted to our maternity service at 25 weeks of gestation. The patient had no history of hemorrhage or abnormal bleeding, and the clinical examination was unremarkable.

Solid-Phase Synthesis of Caged Luminescent Peptides via Side Chain Anchoring.

The synthesis of caged luminescent peptide substrates remains challenging, especially when libraries of the substrates are required. Most currently available synthetic methods rely on a solution-phase approach, which is less suited for parallel synthesis purposes. We herein present a solid-phase peptide synthesis (SPPS) method for the synthesis of caged aminoluciferin peptides via side chain anchoring of the P residue.

Indirect treatment comparisons of the gene therapy etranacogene dezaparvovec versus extended half-life factor IX therapies for severe or moderately severe haemophilia B.

Introduction: Etranacogene dezaparvovec gene therapy for haemophilia B demonstrated superior efficacy at 24 months in reducing bleeds versus a ≥6-month lead-in period of prophylaxis with FIX products in the phase 3 trial, HOPE-B. In the absence of head-to-head comparisons of etranacogene dezaparvovec versus FIX products, indirect treatment comparisons (ITC) can be used.

Aim: To compare the efficacy of etranacogene dezaparvovec versus rIX-FP, rFIXFc and N9-GP using ITC, and support HOPE-B results.

Synthesis and Evaluation of Glycosyl Luciferins.

Measuring glycosidase activity is important to monitor any aberrations in carbohydrate hydrolase activity, but also for the screening of potential glycosidase inhibitors. To this end, synthetic substrates are needed which provide an enzyme-dependent read-out upon hydrolysis by the glycosidase. Herein, we present two new routes for the synthesis of caged luminescent carbohydrates, which can be used for determining glycosidase activity with a luminescent reporter molecule.

Accreditation model of European Haemophilia Centres in the era of novel treatments and gene therapy.

Introduction: The international certification of haemophilia centres in Europe is run by the European Association of Haemophilia and Allied Disorders (EAHAD) and European Haemophilia Consortium (EHC) since 2013. The centres are designated as European Haemophilia Comprehensive Care Centres (EHCCC) or European Haemophilia Treatment Centres (EHTC), based on the specific requirements which evaluate centres' ability to provide care for patients with haemophilia and allied disorders.

Aim: To establish the new protocol for accreditation of European Haemophilia Centres.

French National Diagnostic and Care Protocol for antiphospholipid syndrome in adults and children.

Antiphospholipid syndrome (APS) is a chronic autoimmune disease involving vascular thrombosis and/or obstetric morbidity and persistent antibodies to phospholipids or certain phospholipid-associated proteins. It is a rare condition in adults and even rarer in children. The diagnosis of APS can be facilitated by the use of classification criteria based on a combination of clinical and biological features.

Evaluation of the care pathway in the context of the dispensing of emicizumab (Hemlibra) in community and hospital pharmacies in France: A patient satisfaction survey.

Introduction: Since June 2021 in France, patients with haemophilia A with anti-factor VIII inhibitors and patients with severe haemophilia A without anti-factor VIII inhibitors, and treated with emicizumab (Hemlibra), have to choose the dispensing circuit community or hospital pharmacy.

Aim: To evaluate satisfaction of patients whether they choose dispensation from a community pharmacy or retained dispensation from the hospital pharmacy, to understand the main motivation for choosing the community or the hospital pharmacy.

Methods: All patients living in France, regardless of age, were eligible to participate.

Health-related quality of life following valoctocogene roxaparvovec gene therapy for severe hemophilia A in the phase 3 trial GENEr8-1.

Background: Severe hemophilia A (HA) negatively impacts health-related quality of life (HRQOL).

Objectives: We aimed to analyze HRQOL in adult men with severe HA without inhibitors after valoctocogene roxaparvovec gene transfer in the phase 3 trial GENEr8-1.

Methods: Participant-reported outcomes were the hemophilia-specific quality of life questionnaire for adults (Haemo-QOL-A), the EQ-5D-5L instrument, the Hemophilia Activities List (HAL), and the Work Productivity and Activity Impairment Questionnaire: Hemophilia Specific (WPAI+CIQ:HS).

Women with severe postpartum hemorrhage have a decreased endogenous thrombin potential before delivery.

Background: Severe postpartum hemorrhage (PPH), defined as a blood loss ≥1000 mL, is associated with maternal morbidity and mortality.

Objectives: We aimed at characterizing coagulation properties of predelivery plasmas from pregnant women with thrombin generation assay and hemostatic biomarkers (plasminogen activator inhibitor-1, tissue factor [TF], and thrombomodulin).

Methods: A nested case-control study was conducted within the "Study of Biological Determinants of Bleeding Postpartum," a French prospective cohort study, in order to compare women with severe PPH (cases) and controls matched for age, body mass index, term, and mode of delivery.

Simoctocog alfa (Nuwiq®) in previously untreated patients with severe haemophilia A-Final efficacy and safety results from the NuProtect study.

Introduction: Simoctocog alfa (Nuwiq®) is a 4th generation recombinant FVIII with proven efficacy for the prevention and treatment of bleeding episodes (BEs) in previously treated patients with severe haemophilia A. The NuProtect study assessed the immunogenicity, efficacy and safety of simoctocog alfa in 108 previously untreated patients (PUPs). The incidence of high-titre inhibitors was 16.

Real-world evidence on efmoroctocog alfa in patients with haemophilia A: A systematic literature review of treatment experience in Europe.

Introduction: The real-world effectiveness of the efmoroctocog alfa (recombinant FVIII Fc fusion protein, a rFVIIIFc) has been investigated in numerous studies, however, currently, there exists no comprehensive collection of the existing real-world evidence (RWE) on the performance of prophylactic use of rFVIIIFc.

Aim: The aims of this systematic literature study were to identify, review, evaluate and collate the RWE of prophylactic rFVIIIFc for patients with haemophilia A reported in Europe.

Methods: We searched Medline and Embase from 2014 to February 2022 to identify publications reporting the effectiveness of rFVIIIFc in patients with haemophilia A.

Obstetrical complications in hereditary fibrinogen disorders: the Fibrinogest study.

Background: Women with hereditary fibrinogen disorders (HFDs) seem to be at an increased risk of adverse obstetrical outcomes, but epidemiologic data are limited.

Objectives: We aimed to determine the prevalence of pregnancy complications; the modalities and management of delivery; and the postpartum events in women with hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia.

Methods: We conducted a retrospective and prospective multicentric international study.

Fitusiran prophylaxis in people with severe haemophilia A or haemophilia B without inhibitors (ATLAS-A/B): a multicentre, open-label, randomised, phase 3 trial.

Background: Fitusiran, a subcutaneous investigational siRNA therapeutic, targets antithrombin with the goal of rebalancing haemostasis in people with haemophilia A or haemophilia B, regardless of inhibitor status. We aimed to evaluate the efficacy and safety of fitusiran prophylaxis in people with severe haemophilia without inhibitors.

Methods: This multicentre, open-label, randomised phase 3 study was conducted at 45 sites in 17 countries.

The use of prothrombin complex concentrate in chronic liver disease: A review of the literature.

Patients with chronic liver disease (CLD) and cirrhosis present a rebalanced hemostatic system in the three phases of haemostasis. This balance is however unstable and can easily tip towards bleeding or thrombosis. Management of both spontaneous bleeding and bleeding during invasive procedures remains a challenge in this patient population.