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.

Dysfibrinogenemia and hypofibrinogenemia - Spectrum of pathogenic variants in Slovak patients.

Introduction: Congenital hypofibrinogenemia (CH) and congenital dysfibrinogenemia (CD) are rare coagulation disorders caused by quantitative or qualitative defects in the fibrinogen gene. The aim of this study was to characterize the genetic background and the clinical manifestations of congenital fibrinogen disorders in the patients from Slovakia registered at the National Haemophilia Centre.

Materials And Methods: Results of genetic analysis of the fibrinogen genes FGA, FGB and FGG using polymerase chain reaction followed by direct sequencing were evaluated in 36 patients.

Efficacy and safety of damoctocog alfa pegol prophylaxis in patients ⩾40 years with severe haemophilia A and comorbidities: analysis from the PROTECT VIII study.

Background: Advances in treatment have enabled patients with haemophilia A to live longer and therefore may be subjected to comorbidities associated with ageing, in addition to disease-associated morbidities. There have been few reports to date on efficacy and safety of treatment specifically in patients with severe haemophilia A and comorbidities.

Objective: To explore the efficacy and safety of damoctocog alfa pegol prophylaxis in patients with severe haemophilia A aged ⩾40 years with comorbidities of interest.

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.

Expert opinion on current and future prophylaxis therapies aimed at improving protection for people with hemophilia A.

The next frontier in hemophilia A management has arrived. However, questions remain regarding the broader applicability of new and emerging hemophilia A therapies, such as the long-term safety and efficacy of non-factor therapies and optimal regimens for individual patients. With an ever-evolving clinical landscape, it is imperative for physicians to understand how available and future hemophilia A therapies could potentially be integrated into real-life clinical practice to improve patient outcomes.

Prophylaxis in children with haemophilia in an evolving treatment landscape.

Introduction: For children with haemophilia, early initiation of prophylaxis is crucial to prevent life-threatening bleeds and maintain joint health throughout life. Options for prophylaxis have recently increased from replacement therapy with standard or extended half-life coagulation factor products to include other haemostasis products, such as the non-replacement therapy emicizumab.

Aim: To review key factors that determine the choice of prophylaxis in young children.

Confirmed long-term safety and efficacy of prophylactic treatment with BAY 94-9027 in severe haemophilia A: final results of the PROTECT VIII extension study.

Introduction: The phase 2/3 PROTECT VIII main study demonstrated efficacy and safety of BAY 94-9027 (damoctocog alfa pegol; Jivi ), a B-domain-deleted recombinant factor VIII (FVIII), site-specifically PEGylated to extend its half-life.

Aim: To report the final efficacy and safety data for BAY 94-9027 from the PROTECT VIII extension.

Methods: Previously treated males aged 12-65 years with severe haemophilia A (FVIII <1%) who completed the multicentre, open-label PROTECT VIII main study were eligible for the extension.

Efficacy of prehospital administration of fibrinogen concentrate in trauma patients bleeding or presumed to bleed (FIinTIC): A multicentre, double-blind, placebo-controlled, randomised pilot study.

Background: Trauma-induced coagulopathy (TIC) substantially contributes to mortality in bleeding trauma patients.

Objective: The aim of the study was to administer fibrinogen concentrate in the prehospital setting to improve blood clot stability in trauma patients bleeding or presumed to bleed.

Design: A prospective, randomised, placebo-controlled, double-blinded, international clinical trial.

Turoctocog alfa pegol provides effective management for major and minor surgical procedures in patients across all age groups with severe haemophilia A: Full data set from the pathfinder 3 and 5 phase III trials.

Introduction: Turoctocog alfa pegol is a glycoPEGylated recombinant factor VIII (FVIII) with an extended half-life developed for prophylaxis, treatment of bleeds and perioperative management in patients with haemophilia A.

Aim: Evaluate the efficacy and safety of turoctocog alfa pegol treatment for major and minor surgeries in the pathfinder 3 and 5 phase III trials.

Methods: Adults/adolescents aged ≥12 years with severe haemophilia A (FVIII <1%) received perioperative turoctocog alfa pegol treatment planned to achieve FVIII activity levels >80% during major surgery (pathfinder 3).

Long-term analysis of the benefit of prophylaxis for adult patients with severe or moderate haemophilia A.

Introduction: Prophylaxis with factor VIII (FVIII) concentrates in children with haemophilia A (HA) is current standard of care. The benefit of prophylactic treatment for adult HA patients is not commonly accepted.

Aim: To investigate the benefit of prophylaxis over on-demand treatment in adult and elderly patients with severe or non-severe HA in a real-life setting.

von Willebrand factor alloantibodies in type 3 von Willebrand disease.

: The development of neutralizing antibodies is a rare complication of von Willebrand disease treatment. In major surgical procedures for severe forms of the disease, the recognition of ineffective therapy and alternative treatment protocols are lifesaving. We report the case of a 6-year-old girl with type 3 von Willebrand disease in whom inhibitors were sought due to ineffective haemostasis together with lower than expected von Willebrand factor (VWF) recoveries after a surgical procedure.

Bodyweight-adjusted rivaroxaban for children with venous thromboembolism (EINSTEIN-Jr): results from three multicentre, single-arm, phase 2 studies.

Background: Rivaroxaban has been shown to be efficacious for treatment of venous thromboembolism in adults, and has a reduced risk of bleeding compared with standard anticoagulants. We aimed to develop paediatric rivaroxaban regimens for the treatment of venous thromboembolism in children and adolescents.

Methods: In this phase 2 programme, we did three studies to evaluate rivaroxaban treatment in children younger than 6 months, aged 6 months to 5 years, and aged 6-17 years.

The changing face of immune tolerance induction in haemophilia A with the advent of emicizumab.

Introduction: As a result of the new treatment paradigm that the haemophilia community will face with the availability of novel (non-factor) therapies, an updated consensus on ITI recommendations and inhibitor management strategies is needed.

Aim: The Future of Immunotolerance Treatment (FIT) group was established to contemplate, determine and recommend the best management options for patients with haemophilia A and inhibitors.

Discussion And Conclusions: Despite the considerable success of emicizumab in the management of inhibitor patients, the FIT group still sees the importance of eradicating inhibitors.

Vaccinations are not associated with inhibitor development in boys with severe haemophilia A.

Background: Inhibitor development in previously untreated patients (PUPs) with severe haemophilia A is a multifactorial event. It is unknown whether paediatric vaccinations given in close proximity to factor VIII (FVIII) are associated with inhibitor development.

Objective: To assess whether paediatric vaccinations in close proximity to FVIII within the first 75 exposure days (EDs) are associated with inhibitor development in PUPs with severe haemophilia A.

Continuous infusion of coagulation factor concentrates during intensive treatment.

In clinical management of bleeds and surgical procedures in patients suffering from bleeding disorders either repetitive bolus injections (BI) or continuous infusion (CI) can be used for coagulation factor replacement. Continuous infusion seems to be an attractive route of administration and may be considered if replacement therapy is required for more than 3 days. The strongest argument favouring continuous infusion is its superiority in providing the patient with a safe and constant level of the deficient coagulation factor by balancing input with clearance.

Intracranial haemorrhage in children and adolescents with severe haemophilia A or B - the impact of prophylactic treatment.

The discussion of prophylactic therapy in haemophilia is largely focused on joint outcomes. The impact of prophylactic therapy on intracranial haemorrhage (ICH) is less known. This study aimed to analyse ICH in children with haemophilia, with a focus on different prophylaxis regimens and sequelae of ICH.

PK-guided personalized prophylaxis with Nuwiq (human-cl rhFVIII) in adults with severe haemophilia A.

Introduction: Nuwiq (human-cl rhFVIII) is a 4 generation recombinant human FVIII, without chemical modification or protein fusion, produced in a human cell-line.

Aims/methods: This study (NuPreviq) was a prospective, open-label, multicentre, phase IIIb study of the efficacy and safety of personalized prophylaxis with Nuwiq in 66 previously treated adults with severe haemophilia A. NuPreviq had three phases: (i) a 72-h pharmacokinetic (PK) phase; (ii) a 1-3 month standard prophylaxis phase; and (iii) a 6-month personalized prophylaxis phase.

Efficacy and safety of BAY 81-8973, a full-length recombinant factor VIII: results from the LEOPOLD I trial.

Introduction: BAY 81-8973 (Kovaltry(®) ) is a full-length, unmodified recombinant human factor VIII (FVIII) with the same amino acid sequence as sucrose-formulated recombinant FVIII and is produced using additional advanced manufacturing technologies.

Aim: To demonstrate efficacy and safety of BAY 81-8973 for treatment of bleeds and as prophylaxis based on two different potency assignments.

Methods: In LEOPOLD I (ClinicalTrials.

Women with congenital factor VII deficiency: clinical phenotype and treatment options from two international studies.

Introduction: A paucity of data exists on the incidence, diagnosis and treatment of bleeding in women with inherited factor VII (FVII) deficiency.

Aim: Here we report results of a comprehensive analysis from two international registries of patients with inherited FVII deficiency, depicting the clinical picture of this disorder in women and describing any gender-related differences.

Methods: A comprehensive analysis of two fully compatible, international registries of patients with inherited FVII deficiency (International Registry of Factor VII deficiency, IRF7; Seven Treatment Evaluation Registry, STER) was performed.

Impact of high-risk thrombophilia status on recurrence among children with a first non-central-venous-catheter-associated VTE: an observational multicentre cohort study.

Deficiency of antithrombin (AT), protein C (PC) or protein S (PS) constitutes a major risk factor for venous thromboembolism (VTE). Individuals at high risk for recurrence who benefit from screening need to be identified. The primary study objective was to determine the individual recurrence risk among children with a first non-central-venous-catheter-associated VTE with respect to their thrombophilia status and to evaluate if the clinical presentation at first VTE onset differs between children with AT, PC or PS deficiency versus no thrombophilia.

Beyond stopping the bleed: short-term episodic prophylaxis with recombinant activated factor FVII in haemophilia patients with inhibitors.

Preventing haemarthroses and arthropathy is a major challenge in patients with haemophilia and inhibitors, as treatment options are limited. One potential strategy is short-term episodic prophylaxis, which extends bypassing agent therapy beyond the resolution of bleeding to include the post-bleed inflammatory phase. At the 13 Zürich Haemophilia Forum, an expert panel reviewed the rationale behind this strategy, explored its current use with recombinant activated factor VII (rFVIIa) and considered treatment monitoring and optimisation.