Long-term safety and efficacy of fitusiran prophylaxis, and perioperative management, in people with hemophilia A or B.

Fitusiran is an investigational small interfering RNA therapeutic that targets antithrombin (AT) to rebalance hemostasis in people with hemophilia. Here, we present the results of a completed phase 2 open-label extension study, which evaluated the long-term safety and efficacy of fitusiran in participants with moderate or severe hemophilia A or B, with or without inhibitors. Male participants who had completed the phase 1 study (ClinicalTrials.

Educational needs of patients, families, and healthcare professionals to support the patient journey in haemophilia gene therapy in the UK.

With the first gene therapies for haemophilia approved by the European Commission, the US Food and Drug Administration, and the Medicines and Healthcare products Regulatory Agency, it is important to consider the remaining unmet needs and challenges that may arise throughout patients' treatment journeys. We discuss existing unmet needs and important considerations prior to, during, and following haemophilia gene therapy treatment in the UK, and propose potential next steps. Key areas for attention are education, psychological support, and guidance on implementation.

Pilot study to evaluate hypercoagulation and inflammation using rotational thromboelastometry and calprotectin in COVID-19 patients.

Introduction: Abnormal coagulation and inflammation are hallmarks of SARs-COV-19. Stratifying affected patients on admission to hospital may help identify those who at are risk of developing severe disease early on. Rotational Thromboelastometry (ROTEM) is a point of care test that can be used to measure abnormal coagulation and calprotectin is a measure of inflammation.

Gynaecological management of women with inherited bleeding disorders. A UK Haemophilia Centres Doctors' Organisation Guideline.

Women with inherited bleeding disorders (IBDs) may present to healthcare professionals in a variety of ways and commonly will be encountered by either haematology or gynaecology services. Heavy menstrual bleeding is very often the first manifestation of an IBD. There is a wide variation in severity of bleeding for women with IBD and diagnosis and subsequent management of their condition requires multidisciplinary specialised care which is tailored to the individual and includes excellent cross-specialty communication between gynaecology and haematology teams.

A single centre, open label, pilot study evaluating the effect of intra-articular hyaluronic acid injection on pain and functionality when injected into the ankle (tibio-talar and sub-talar) joint in patients with haemophilic arthropathy.

Aims: Ankle arthropathy commonly affects persons with haemophilia (PWH). Joint damage causes loss of movement, pain and reduced function. Current treatments are limited.

Seroprevalence to adeno-associated virus type 6 in people with hemophilia B from a UK adult cohort.

Background: Gene therapy shows promise as a potential "cure" for hemophilia A and B. Adeno-associated virus (AAV) vectors are the leading platform to deliver modified genetic code of factor VIII or IX to the liver effecting endogenous production. Patient exposure to wild-type AAV leads to the formation of neutralizing factors, which can prevent successful transduction.

The Hemophilia Joint Health Score version 2.1 Validation in Adult Patients Study: A multicenter international study.

Background: The Hemophilia Joint Health Score (HJHS) was developed and validated to detect arthropathy in children. Additional evidence is required to show validity in adults. We studied the convergent and discriminant construct validity of the HJHS version 2.

Haemophilia Carriers Experience Study (CARES): A mixed method exploration into the experience of women who are carriers of Haemophilia.

Introduction: Haemophilia research has traditionally focused on patients diagnosed with haemophilia and although research priorities are rapidly changing, there is still a lot more we need to understand about the experiences and psychosocial issues facing women who are diagnosed as carriers of haemophilia (Haemophilia, https://doi.org/10.1111/hae.

An overview of the pathfinder clinical trials program: Long-term efficacy and safety of N8-GP in patients with hemophilia A.

N8-GP (turoctocog alfa pegol, Esperoct ; Novo Nordisk A/S, Bagsvaerd, Denmark) is a state-of-the-art, extended half-life factor VIII (FVIII) molecule used for prophylactic and on-demand treatment of patients with hemophilia A. The pathfinder clinical trial program, which began with the pathfinder1 trial in 2010, was developed to assess the long-term efficacy and safety of N8-GP in children, adolescents, and adults. The pivotal pathfinder2 (adolescents and adults) and pathfinder5 (children) trials were completed in late 2018, and comprehensive analyses of the end-of-trial results are published together with this article as part of an N8-GP Supplement.

A Novel, Enriched Population Pharmacokinetic Model for Recombinant Factor VIII-Fc Fusion Protein Concentrate in Hemophilia A Patients.

Background:  The currently published population pharmacokinetic (PK) models used for PK-guided dosing in hemophilia patients are based on clinical trial data and usually not externally validated in clinical practice. The aim of this study was to validate a published model for recombinant factor VIII-Fc fusion protein (rFVIII-Fc) concentrate and to develop an enriched model using independently collected clinical data if required.

Methods:  Clinical data from hemophilia A patients treated with rFVIII-Fc concentrate (Elocta) participating in the United Kingdom Extended Half-Life Outcomes Registry were collected.

Real-World Utilisation and Bleed Rates in Patients with Haemophilia B Who Switched to Recombinant Factor IX Fusion Protein (rIX-FP): A Retrospective International Analysis.

Introduction: Despite the well-documented benefits of prophylaxis, treatment burden is still a barrier to adherence in patients with haemophilia. An extended half-life fusion protein linking recombinant FIX (rFIX) with human albumin (rIX-FP) has been developed for the treatment of patients with haemophilia B and is indicated for dosing up to every 14 days. This analysis evaluated real-world outcomes in patients switching to rIX-FP from the previous FIX product in Italy, Belgium and the UK.

Next-generation sequencing for the diagnosis of MYH9-RD: Predicting pathogenic variants.

The heterogeneous manifestations of MYH9-related disorder (MYH9-RD), characterized by macrothrombocytopenia, Döhle-like inclusion bodies in leukocytes, bleeding of variable severity with, in some cases, ear, eye, kidney, and liver involvement, make the diagnosis for these patients still challenging in clinical practice. We collected phenotypic data and analyzed the genetic variants in more than 3,000 patients with a bleeding or platelet disorder. Patients were enrolled in the BRIDGE-BPD and ThromboGenomics Projects and their samples processed by high throughput sequencing (HTS).

Germline mutations in the transcription factor IKZF5 cause thrombocytopenia.

To identify novel causes of hereditary thrombocytopenia, we performed a genetic association analysis of whole-genome sequencing data from 13 037 individuals enrolled in the National Institute for Health Research (NIHR) BioResource, including 233 cases with isolated thrombocytopenia. We found an association between rare variants in the transcription factor-encoding gene IKZF5 and thrombocytopenia. We report 5 causal missense variants in or near IKZF5 zinc fingers, of which 2 occurred de novo and 3 co-segregated in 3 pedigrees.

Case 37: Neutropenia and macrocytosis in a middle-aged man.

A myelodysplastic syndrome (MDS) was suspected in a middle-aged man who presented with neutropenia and macrocytosis. The correct non-neoplastic diagnosis was not made for 5 years. It is of crucial importance to exclude treatable causes of cytopenia and dysplasia when MDS is suspected.