Ex vivo evaluation of the effect of plasma-derived factor VIII/von Willebrand factor in patients with severe hemophilia A on emicizumab prophylaxis.

Hemophilia A (HA) patients under emicizumab prophylaxis may require the concomitant use of procoagulant factors for breakthrough bleedings or immune tolerance induction (ITI). The aim of this study is to evaluate the ex vivo procoagulant effect of plasma-derived FVIII concentrates containing von Willebrand factor (pdFVIII/VWF) in samples from patients with severe HA without inhibitors on emicizumab prophylaxis. Samples from healthy controls (HC) and HA patients were drawn in sodium citrate plus corn trypsin inhibitor tubes and spiked with increasing concentrations of pdFVIII/VWF concentrates (10-400 IU/dL) (Fanhdi/Alphanate, Grifols), activated prothrombin complex concentrate (aPCC, 0.

Utilizing artificial intelligence for the detection of hemarthrosis in hemophilia using point-of-care ultrasonography.

Background: Recurrent hemarthrosis and resultant hemophilic arthropathy are significant causes of morbidity in persons with hemophilia, despite the marked evolution of hemophilia care. Prevention, timely diagnosis, and treatment of bleeding episodes are key. However, a physical examination or a patient's assessment of musculoskeletal pain may not accurately identify a joint bleed.

Bleed treatment with eptacog beta (rFVIIa) results in a low incidence of rebleeding in adult and adolescent patients with haemophilia A or B with inhibitors.

Introduction: Eptacog beta is a novel human recombinant FVIIa approved for use in the United States, European Union, United Kingdom and Mexico for the treatment and control of bleeding in patients with haemophilia A or B with inhibitors (≥12 years). It is also indicated for perioperative care in the same patient population in Europe and the United Kingdom.

Aim: To assess the incidence of rebleeding and review treatment outcomes in subjects with haemophilia with inhibitors enrolled in the phase 3 PERSEPT 1 clinical trial.

Contrasting Approaches in the Implementation of GRADE Methodology in Guidelines for Haemophilia and Von Willebrand Disease.

Introduction: The 2024 ISTH clinical practice guideline (CPG) for treatment of congenital haemophilia, the NBDF-McMaster Guideline on Care Models for Haemophilia Management, and ASH ISTH NBDF WFH guidelines on the diagnosis and management of VWD all utilised GRADE methodology.

Aim: Discuss missed opportunities and the methodological approach of the ISTH Guideline in contrast to how GRADE was previously applied in rare diseases.

Methods: Critically analyse the methodology of each guideline along with best practices in the use of GRADE.

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.

Non-factor Therapies for Hemophilia: Achievements and Perspectives.

Non-factor replacement therapies (NFTs) have been developed to address the limitations of conventional replacement therapies, aiming to improve hemostasis and provide enhanced protection against bleeding episodes and long-term joint damage for patients both with and without inhibitors. Factor VIII (FVIII)-mimetic agents, such as emicizumab, have transformed the management of hemophilia A with inhibitors, offering a lower treatment burden and an effective alternative for those without inhibitors as well. Rebalancing agents, including anti-tissular factor pathway inhibitor agents (concizumab and marstacimab) and serpin inhibitors like fitusiran, have shown promising efficacy for patients with hemophilia B with inhibitors and other hemophilia subtypes.

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.

Teenagers and Adolescents with Hemophilia-Need for a Specific Approach.

Adolescents with hemophilia are a patient population with special requirements, having to manage their condition alongside the typical challenges of adolescence. Given the psychosocial impact of hemophilia and a desire to fit in with non-hemophilic peers, they may perceive treatment as more of a burden than a benefit. This can result in low adherence and a high risk of hemophilia-related complications.

Emicizumab is efficacious in people with hemophilia A with comorbidities aged ≥50 years: analysis of 4 phase III trials.

Background: The treatment of older people with hemophilia A (HA) can be complicated by comorbidities.

Objectives: This post hoc analysis evaluates the efficacy and safety of emicizumab in people with HA aged ≥50 years with cardiovascular (CV) risk factors or HIV and/or hepatitis C virus (HCV) infection.

Methods: The HAVEN 1 (NCT02622321), HAVEN 3 (NCT02847637), HAVEN 4 (NCT03020160), and STASEY (NCT03191799) studies enrolled adults/adolescents with severe HA.

Management of Urgent Bleeding in Patients with Hemophilia A: Focus on the Use of Emicizumab.

Management of patients with hemophilia A (HA) requires the knowledge and experience of specialized health care professionals. However, these patients may need to be attended in emergencies, outside the referral hospital, where health care professionals do not know about hemophilia and/or new innovative treatments. This study aimed to develop a simple and practical algorithm that could be used in emergency situations by nonspecialized treaters in HA and bleeding with or without factor VIII (FVIII) inhibitors under emicizumab prophylaxis.

Predicting joint involvement through tailored prophylaxis in severe haemophilia A, is it possible?

Introduction: Tailored prophylaxis is the current treatment regimen for patients with severe haemophilia A. Recently, published guidelines describe two possible approaches, based on clinical characteristics or estimation of pharmacokinetic parameters. However, both have strengths and weaknesses, and their characteristics need to be integrated to optimize treatment appropriately.

Long-term outcomes with emicizumab in hemophilia A without inhibitors: results from the HAVEN 3 and 4 studies.

Background: Emicizumab, a bispecific monoclonal antibody, bridges activated factor (F) IX and FX, mimicking the function of missing or deficient activated FVIII in people with hemophilia A (HA).

Objectives: To evaluate the long-term efficacy and safety of emicizumab prophylaxis in people with HA without FVIII inhibitors in the HAVEN 3 and 4 studies.

Methods: HAVEN 3 and 4 were phase 3 open-label studies.

Outcomes and outcome measures.

Introduction: Advances in haemophilia treatment have resulted in a near-normal life expectancy, lower burden of bleeding and treatment, and improved quality of life in high-income countries. Bleeding rate is approaching zero and novel parameters should be evaluated to assess the efficacy of treatment not only from the clinical point of view by using new methodologies (e.g.

Knee replacement surgery in a patient with acquired von Willebrand disease: a case study with recommendations for patient management.

Introduction And Importance: Acquired von Willebrand disease (AvWD) is a rare underdiagnosed bleeding disorder caused by alterations in the levels of the major blood-clotting protein von Willebrand factor (vWF). The clinical and laboratory parameters of AvWD are similar to congenital vWD, but it is found in individuals with no positive family history with no underlying genetic basis. The disease remains multifactorial and incompletely understood.

Arthroscopic ankle surgery in people with haemophilia.

Introduction: People with haemophilia (PWH) not administered primary haematological prophylaxis since childhood, that is, those treated haematologically on demand or not treated at all, often experience the degeneration of the ankles, leading to pain and functional impairment.

Aim: To analyse the outcomes and complications of arthroscopic ankle surgery performed on PWH.

Methods: For this narrative review of the literature, a search was conducted in PubMed on 2, December 2023, using the keywords "haemophilia", "ankle" and "arthroscopy".

Eptacog beta for the management of patients with haemophilia A and B with inhibitors: A European perspective.

Eptacog beta (activated), a recombinant human factor VIIa (rFVIIa), was approved by the US Food and Drug Administration (FDA) in 2020 (SEVENFACT®, LFB & HEMA Biologics) and the European Medicines Agency (EMA) in 2022 (CEVENFACTA®, LFB). In Europe, eptacog beta is indicated for the treatment of bleeds and the prevention of bleeds during surgery or invasive procedures in adults and adolescents (≥12 years old) with congenital haemophilia A or B with high-titre inhibitors (≥5 BU) or with low-titre inhibitors who are expected to have a high anamnestic response to factor VIII or factor IX, or to be refractory to increased dosing of these factors. The efficacy and safety of eptacog beta were evaluated in three Phase III clinical studies, PERSEPT 1, 2 and 3.

Pharmacokinetics and coagulation biomarkers in children and adults with hemophilia A receiving emicizumab prophylaxis every 1, 2, or 4 weeks.

Background: Emicizumab is a bispecific antibody that bridges activated factor (F)IX and FX, mimicking the function of missing activated FVIII and thus improving hemostasis in people with hemophilia A. The efficacy and safety of emicizumab were demonstrated in 4 phase III clinical trials (HAVEN 1-4).

Objectives: Here, we describe pharmacokinetics (PKs), pharmacodynamics (PDs), and exploratory safety biomarkers in HAVEN 1 to 4.

A post hoc comparative real-world analysis of HEAD-US score for joint health assessment of patients with severe haemophilia A and B in Spain.

Aim: Joint damage due to haemarthrosis can be effectively monitored with point-of care ultrasound using the Haemophilia Early Arthropathy Detection with US (HEAD-US) scoring system. A post hoc comparative analysis of the joint status of patients with severe haemophilia A (HA) or B (HB) was performed.

Methods: The databases of two observational, cross-sectional studies that recruited patients with HA or HB from 12 Spanish centres were analysed to compare the status of the elbows, knees and ankles in patients with severe disease according to treatment modality.

Emicizumab prophylaxis in infants with hemophilia A (HAVEN 7): primary analysis of a phase 3b open-label trial.

Subcutaneous emicizumab enables prophylaxis for people with hemophilia A (HA) from birth, potentially reducing risk of bleeding and intracranial hemorrhage (ICH). HAVEN 7 (NCT04431726) is the first clinical trial of emicizumab dedicated to infants, designed to investigate the efficacy, safety, pharmacokinetics, and pharmacodynamics of emicizumab in those aged ≤12 months with severe HA without factor VIII (FVIII) inhibitors. Participants in this phase 3b trial received emicizumab 3 mg/kg maintenance dose every 2 weeks for 52 weeks and are continuing emicizumab during the 7-year long-term follow-up.