Patient Experience With Efanesoctocog Alfa for Severe Hemophilia A: Results From the XTEND-1 Phase 3 Clinical Study Exit Interviews.

Purpose: Hemophilia A is a rare bleeding disorder that leads to recurrent hemarthrosis, which can ultimately result in reduced mobility and poor quality of life. Qualitative exit interviews provide insights into patient perspectives and support the interpretation of quantitative trial data, such as patient-reported outcome measures. In the Phase 3 XTEND-1 study (NCT04161495) of efanesoctocog alfa in participants with severe hemophilia A, exit interviews were conducted to understand pre- and post-study experiences with pain and physical functioning and to evaluate participants' treatment experiences.

Comprehensive genomic filtering algorithm to expose the cause of skewed X chromosome inactivation. The proof of concept in female haemophilia expression.

Background: Exploring the expression of X linked disorders like haemophilia A (HA) in females involves understanding the balance achieved through X chromosome inactivation (XCI). Skewed XCI (SXCI) may be involved in symptomatic HA carriers. We aimed to develop an approach for dissecting the specific cause of SXCI and verify its value in HA.

The hidden joint in children with haemophilia on prophylaxis.

Unlabelled: Prophylaxis is the gold standard treatment for children with haemophilia (CWH). MRI studies revealed joint damage, even with this treatment; this suggests the presence of subclinical bleeding. In the case of children with haemophilia, it is relevant to detect early signs of joint damage, as this allows the medical team to provide the appropriate treatment and follow-up, in order to avoid arthropathy development and its consequences.

Haemophilia B, severe childhood obesity and other extra-haematological features associated with similar 4Mb-deletions on Xq27: Clinical findings, molecular insights and literature update.

Introduction: Haemophilia B (HB) is associated with pathogenic variants in F9. Hemizygous deletions encompassing the entire F9 and proximate genes may express extra-haematological clinical phenotypes.

Aim: To analyse the genotype/phenotype correlations in two unrelated boys with severe early childhood obesity (SCO), global developmental delay (GDD) and similar bleeding phenotype associated with comparable Xq27 deletions spanning the entire F9 and proximate genes, and characterise the pathogenic events estimating the most likely mutational mechanism involved.

How mild is mild haemophilia?

Introduction: People with mild haemophilia (PWMH) experience sporadic bleeds and are less likely to receive an early diagnosis, appropriate treatment and medical care. Arthropathy is a key determinant of health-related quality of life (QoL), producing pain, limitations in mobility and daily activities. The aim of this study is to evaluate the incidence, risk factors and QoL associated with arthropathy in PWMH.

A multicentre real-world data study to assess the bleeding rate and management of patients with haemophilia A and factor VIII inhibitors in Argentina.

The development of inhibitors against factor VIII (FVIII) concentrates is a severe complication of treatment for patients with haemophilia. We investigated annualized bleeding rates (ABRs) in patients in Argentina with haemophilia A with inhibitors and analysed potential differences between treatment strategies. This multicentre, retrospective, real-world data, cohort design study comprised ambulatory paediatric and adult patients with congenital haemophilia A and FVIII inhibitors treated according to standard clinical practice, with 12-months follow-up.

Clinical and ultrasound evaluation of patients with haemophilia on prophylaxis.

Introduction: Primary prophylaxis is the current gold standard in haemophilia care for the prevention of bleeding and ensuing joint damage. Early detection of joint bleeding, whether symptomatic or subclinical, preferably during childhood, helps prevent joint deterioration and subsequent disability. The aim of this study is to evaluate the level of agreement between the Haemophilia Joint Health Score and the Haemophilia Early Arthropathy Detection with Ultrasound tools in children with severe haemophilia on primary and secondary prophylaxis.

Molecular insights into the mechanism of nonrecurrent F8 structural variants: Full breakpoint characterization and bioinformatics of DNA elements implicated in the upmost severe phenotype in hemophilia A.

Hemophilia A (HA) provides excellent models to analyze genotype-phenotype relationships and mutational mechanisms. NhF8ld's breakpoints were characterized using case-specific DNA-tags, direct- or inverse-polymerase chain reaction amplification, and Sanger sequencing. DNA-break's stimulators (n = 46), interspersed repeats, non-B-DNA, and secondary structures were analyzed around breakpoints versus null hypotheses (E-values) based on computer simulations and base-frequency probabilities.

Inverse PCR to perform long-distance haplotyping: main applications to improve preimplantation genetic diagnosis in hemophilia.

Among other applications of long-distance haplotype phasing in clinical genetics, determination of linked DNA markers as surrogate for problematic structural variants (e.g., repeat-mediated rearrangements) is essential to perform diagnosis from low-quality DNA samples.

A Randomized Trial of Factor VIII and Neutralizing Antibodies in Hemophilia A.

Background: The development of neutralizing anti-factor VIII alloantibodies (inhibitors) in patients with severe hemophilia A may depend on the concentrate used for replacement therapy.

Methods: We conducted a randomized trial to assess the incidence of factor VIII inhibitors among patients treated with plasma-derived factor VIII containing von Willebrand factor or recombinant factor VIII. Patients who met the eligibility criteria (male sex, age <6 years, severe hemophilia A, and no previous treatment with any factor VIII concentrate or only minimal treatment with blood components) were included from 42 sites.

Secondary prophylaxis with rFVIIa in hemophilia and inhibitors: recommendations from an experts committee from Argentina.

Secondary prophylaxis with rFVIIa has been the subject of several publications in the past few years. However, there is no general consensus on how this treatment should be put into practice, as publications have been very heterogeneous in the dosing schedule they report. Furthermore, the mechanism of action of rFVIIa and its short half life have been used as arguments against its role in prophylaxis.

Cytogenetic, FISH, and molecular studies in a case of B-cell chronic lymphocytic leukemia with karyotypic evolution.

We report the clinical, cytogenetic, fluorescence in situ hybridization (FISH) and molecular findings in a 54-yr-old male patient diagnosed with B-cell chronic lymphocytic leukemia (B-CLL), who showed progression to a diffuse large B-cell lymphoma (Richter's syndrome). Genetic studies were performed at diagnosis and during the Richter's transformation (RT). A clonal karyotype with two dicentric chromosomes, psu dic(12,21)(q24;q10) and dic(17,18)(p11.