A phase 1/2 safety and efficacy study of TAK-754 gene therapy: The challenge of achieving durable factor VIII expression in haemophilia A clinical trials.

Introduction: Haemophilia A is an X-linked bleeding disorder resulting from a deficiency of factor VIII (FVIII). To date, multiple gene therapies have entered clinical trials with the goal of providing durable haemostatic protection from a single dose. TAK 754 (BAX 888) is an investigational AAV8-based gene therapy containing a FVIII transgene.

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.

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.

Efanesoctocog Alfa Versus Emicizumab in Adolescent and Adult Patients With Haemophilia A Without Inhibitors.

Introduction: The phase 3 XTEND-1 trial (NCT04161495) demonstrated that efanesoctocog alfa prophylaxis provided superior bleed protection compared with pre-trial factor VIII (FVIII) prophylaxis in patients with severe haemophilia A. The aim of this study was to indirectly compare the efficacy of efanesoctocog alfa with non-factor replacement therapy emicizumab in adolescent and adult patients with severe haemophilia A without inhibitors.

Methods: A systematic literature review was conducted to identify phase 3 trials of emicizumab.

The usefulness of indium-111 platelet scintigraphy beyond predicting efficacy of splenectomy.

There are no clear indicators to predict the outcome of patients with immune thrombocytopenia or the response to drugs. The work of Durand et al. shows that Indium-111 platelet scintigraphy is useful in identifying those patients who will benefit from splenectomy and lays the groundwork for studies demonstrating the increased corticosteroid dependency and rituximab refractoriness of the hepatic platelet sequestration group.

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.

Moderate haemophilia A: Recommendations from a Spanish panel of experts.

Introduction: Diagnosing moderate haemophilia A (MHA) solely based on deficient FVIII protein levels limits its optimal management and delays the initiation of prophylaxis. Updating protocols and incorporating new variables into its diagnosis could prevent underestimating disease severity, avoiding early arthropathies and impairing patients' quality of life.

Aim: To propose recommendations to improve the comprehensive management of people with MHA.

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.

Moving towards Normalization of haemostasis and health equity: Evolving treatment goals for haemophilia A.

Background: Treatment options for people with haemophilia are evolving at a rapid pace and a range of prophylactic treatment options using various technologies are currently available, each with their own distinct safety and efficacy profile.

Treatment Goals: The access to replacement therapy and prophylaxis has driven a dramatic reduction in mortality and resultant increase in life expectancy. Beyond this, the abolition of bleeds and preservation of joint health represent the expected, but rarely attained, goals of haemophilia treatment and care.

Humanistic burden of haemophilia A without inhibitors: A cross-sectional analysis of the HemoLIFE study.

Aim: To evaluate the impact of haemophilia A without inhibitors on humanistic outcomes in patients and caregivers. Herein, we report a cross-sectional analysis of the baseline data of persons with haemophilia (PWH) participating in the prospective study HEMOLIFE.

Methods: These data are part of a prospective, observational, and multicentre study currently being conducted in 20 hospitals in Spain by haematologists.

Simoctocog alfa (Nuwiq) in children: early steps in life's journey for people with severe hemophilia A.

People with severe hemophilia A usually experience their first bleed early in life. In children with severe hemophilia A, primary prophylaxis is recommended to prevent recurrent and potentially life-threatening bleeds that significantly impact day-to-day life. Factor VIII (FVIII) prophylaxis is well-established in children and has been shown to reduce the development of hemophilic arthropathy.

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.

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".

Addressing thrombosis concerns in immune thrombocytopenia: the role of fostamatinib in immune thrombocytopenia management.

Introduction: Immune thrombocytopenia (ITP), a disease that commonly presents with an increased risk of bleeding, can also paradoxically produce an increased risk of thromboembolic events. The risk of thromboembolism can be associated with patient-related factors (e.g.

Assessing coagulopathy and endothelial dysfunction in pediatric venous malformation: A thromboelastometry and syndecan-1 study.

Objective: The occurrence of unpredictable pain crises are the principal determinant of the quality of life for patients with venous malformations (VM). A definite coagulation phenomenon, characterized by an increase in D-dimer levels and the presence of phleboliths within the malformation, has been previously reported. By applying Virchow's triad and evaluating intralesional samples, our objective is to delineate the coagulation profile and the extent of endothelial dysfunction within the malformation.

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.

Safety and efficacy of damoctocog alfa pegol prophylaxis in patients with severe haemophilia A: Results of an interventional, post-marketing study.

Introduction: Damoctocog alfa pegol (BAY 94-9027, Jivi ) is an approved extended half-life factor VIII (FVIII) for treatment of previously treated patients with haemophilia A aged ≥12 years. We report the final results of an interventional, post-marketing study of damoctocog alfa pegol prophylaxis in patients with severe haemophilia A.

Methods: In this open-label, interventional, post-marketing, phase 4 trial (NCT04085458), previously FVIII-treated patients with severe haemophilia A aged ≥18 years received damoctocog alfa pegol for ≥100 exposure days (EDs).