Real-world Effectiveness of Lanadelumab in Hereditary Angioedema: Multi-country INTEGRATED Observational Study.

Background: Hereditary angioedema (HAE) is a rare genetic disease characterized by recurrent episodes of cutaneous or subcutaneous edema. There is clinical need for treatments that reduce the rate of HAE attacks in patients.

Objectives: Primary objectives were to evaluate the effectiveness of lanadelumab on attack free rate (AFR; proportion of patients who had zero HAE attacks), and on every two weeks (Q2W) and every four weeks (Q4W) adjustments on AFR.

Expert Opinion for Defining a Severe Bleeding Phenotype to Guide Prophylaxis in Patients with Nonsevere Hemophilia.

Prophylaxis is the standard of care for patients with severe hemophilia, patients with moderate hemophilia, or those with another congenital bleeding disorder that is associated with a severe bleeding phenotype and/or a high risk of spontaneous life-threatening bleeding. Patients with nonsevere hemophilia (factor VIII [FVIII] ≥ 1%) may also have a bleeding phenotype that requires prophylaxis. To date, however, there are no clear criteria as to when prophylaxis is indicated in these patients.

Pregnancy loss in individuals with von Willebrand disease and unspecified mucocutaneous bleeding disorders: a multicenter cohort study.

Background: While bleeding around pregnancy is well described in von Willebrand disease (VWD), the risk of pregnancy loss is less certain.

Objectives: We aimed to describe the frequency of pregnancy loss in females with VWD compared with those with a similar mucocutaneous bleeding phenotype and no VWD or compared with nonbleeding disorder controls.

Methods: Female patients were consecutively approached in 8 specialty bleeding disorder clinics between 2014 and 2023.

Pharmacokinetics of Efmoroctocog alfa by Two-Compartment Model Highlights Hemophilia A Patients with Biphasic Decay, Long Mean Residence Time, and Beta Half-Life.

A compartmental pharmacokinetics (PK) analysis of new extended half-life FVIII concentrates has never been performed in a large cohort of hemophilia patients. An improved PK analysis of individual outcomes may help to tailor hemophilia replacement treatment. PK outcomes after the infusion of a standard single dose of Efmoroctocog alfa were collected from 173 patients with severe/moderately severe hemophilia A in 11 Italian hemophilia centers.

Liver-related aspects of valoctocogene roxaparvovec gene therapy for hemophilia A: expert guidance for clinical practice.

Adeno-associated virus-based gene therapy (valoctocogene roxaparvovec) is an attractive treatment for hemophilia A. Careful clinical management is required to minimize the risk of hepatotoxicity, including assessment of baseline liver condition to determine treatment eligibility and monitoring liver function after gene therapy. This article describes recommendations (developed by a group of hemophilia experts) on hepatic function monitoring before and after gene therapy.

Genetics and Epigenetics in Acquired Hemophilia A: From Bench to Bedside.

Acquired hemophilia A (AHA) is a bleeding disorder characterized by the immunological inhibition of factor VIII (FVIII) of the hemostatic pathway leading to hemorrhagic events. Different domains of FVIII are the target of autoantibodies (mainly immunoglobulin (Ig) G) leading to the deficiency of FVIII. Several factors have been associated with the activation of the auto-immunity towards FVIII.

florio HAEMO: A Longitudinal Survey of Patient Preference, Adherence and Wearable Functionality in Central Europe.

Introduction: florio HAEMO is a hemophilia treatment monitoring application (app) offering activity tracking and wearable device connectivity. Its use might support everyday activities for people with hemophilia. The aim of this study was to evaluate user satisfaction, long-term usage and the impact on data entry when pairing a wearable with a hemophilia monitoring app.

Haemophilia care in Asia: Learning from clinical practice in some Asian countries.

Background: The healthcare systems in Asia vary greatly due to the socio-economic and cultural diversities which impact haemophilia management.

Methods: An advisory board meeting was conducted with experts in haemophilia care from Asia to understand the heterogeneity in clinical practices and care provision in the region.

Findings: The overall prevalence of haemophilia in Asia ranges between 3 and 8.

Fitusiran prophylaxis in people with hemophilia A or B who switched from prior BPA/CFC prophylaxis: the ATLAS-PPX trial.

Fitusiran, a subcutaneous investigational small interfering RNA therapeutic, targets antithrombin to rebalance hemostasis in people with hemophilia A or B (PwHA/B), irrespective of inhibitor status. This phase 3, open-label study evaluated the efficacy and safety of fitusiran prophylaxis in males aged ≥12 years with hemophilia A or B, with or without inhibitors, who received prior bypassing agent (BPA)/clotting factor concentrate (CFC) prophylaxis. Participants continued their prior BPA/CFC prophylaxis for 6 months before switching to once-monthly 80 mg fitusiran prophylaxis for 7 months (onset and efficacy periods).

Measurement of recombinant porcine factor VIII in patients with congenital haemophilia A and inhibitors in the presence of emicizumab.

Introduction: Recombinant porcine factor VIII (rpFVIII) is a treatment option for break-through bleeds in patients with congenital haemophilia A with inhibitors (CHAwI) on emicizumab. However, there are limited data about the measurement of rpFVIII in the presence of emicizumab.

Aim: To analyse whether rpFVIII can be measured with a chromogenic assay with bovine component (bCSA) in plasma from CHAwI on emicizumab treatment.

Identifying performance-based outcome measures of physical function in people with haemophilia (IPOP).

Introduction: Recent recommendations of core outcome sets for haemophilia highlight the need for including measures of performance-based physical health and physical function sustainability. To date, there is no consensus on what outcomes might be of value to clinicians and patients.

Aim: To identify instruments of performance-based physical function to monitor musculoskeletal health in people with haemophilia that are practical in the clinical setting.

Dilemmas on emicizumab in children with haemophilia A: A survey of strategies from PedNet centres.

Introduction: Haemophilia A care has changed with the introduction of emicizumab. Experience on the youngest children is still scarce and clinical practice varies between haemophilia treatment centres.

Aim: We aimed to assess the current clinical practice on emicizumab prophylaxis within PedNet, a collaborative research platform for paediatricians treating children with haemophilia.

Post hoc longitudinal assessment of the efficacy and safety of recombinant factor IX Fc fusion protein in hemophilia B.

Long-term efficacy and safety of the extended half-life recombinant factor IX Fc fusion protein (rFIXFc) has been established among previously treated patients with severe hemophilia B in 2 phase 3 trials (B-LONG [#NCT01027364] and Kids B-LONG [#NCT01440946]) and a long-term extension study (B-YOND [#NCT01425723]). In this study, we report post hoc analyses of pooled longitudinal data for up to 6.5 years for rFIXFc prophylaxis.

Clinical experience of switching patients with severe hemophilia to rVIII-SingleChain or rIX-FP.

Objective: Prophylaxis treatment is the current standard of care for patients with severe hemophilia. Factor concentrates with improved pharmacokinetics have offered more options for individualizing treatment. The treatment focus may be on increased protection, aiming for higher trough factor levels or longer dosing intervals to reduce the burden of hemophilia.

Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors.

Despite current therapies, there remains an unmet need for treatment for patients with hemophilia. The main parts of two phase 2 trials established clinical proof-of-concept for once-daily, subcutaneous concizumab prophylaxis in patients with hemophilia A/B with inhibitors (HAwI/HBwI; explorer4) and severe hemophilia A without inhibitors (HA; explorer5). Here, we present results from extension parts of these trials, included to evaluate longer term safety and efficacy.

Immune tolerance induction in the era of emicizumab - still the first choice for patients with haemophilia A and inhibitors?

Introduction: The development of inhibitory antibodies is a severe complication of clotting factor replacement therapy in patients with severe haemophilia A (HA). Current World Federation of Hemophilia (WFH) guidelines for haemophilia care indicate that eradication of inhibitors is best achieved through immune tolerance induction (ITI) therapy.

Aim: The European Collaborative Haemophilia Network conducted a survey to determine whether ITI is still used in the routine management of patients with HA, and whether the availability of emicizumab prophylaxis has influenced treatment decisions.

Predictors of inhibitor eradication by primary immune tolerance induction in severe haemophilia A with high responding inhibitors.

Background: Immune tolerance induction (ITI) is the only proven strategy to eradicate factor VIII inhibitors in patients with haemophilia A (HA).

Aim: To identify patients and treatment options with the highest chance of inhibitor eradication by primary ITI.

Patients And Methods: In the frame of the Italian ITI Registry, carried out from 1995 to 2015 (last follow-up 2018), 137 primary ITI courses in severe HA patients (90/137 with poor prognosis) were analysed for predictors of outcome (complete/partial response or failure).

The Pre- and Postoperative Prevalence and Risk Factors of ASA Nonresponse in Vascular Surgery.

Background: An antiplatelet therapy with acetylsalicylic acid (ASA) is prescribed in the prevention of cardiovascular events, but around 24% of ASA takers are resistant to the treatment.

Aim: In this prospective, observational cohort study, we aimed to identify the prevalence and risk factors of ASA nonresponse in patients who underwent vascular surgery.

Methods: The study was conducted in the University hospital in Frankfurt am Main.

Musculoskeletal ultrasound in hemophilia: Results and recommendations from a global survey and consensus meeting.

Introduction: For persons with hemophilia, optimization of joint outcomes is an important unmet need. The aim of this initiative was to determine use of ultrasound in evaluating arthropathy in persons with hemophilia, and to move toward consensus among hemophilia care providers regarding the preferred ultrasound protocols for global adaptation.

Methods: A global survey of hemophilia treatment centers was conducted that focused on understanding how and why ultrasound was being used and endeavored to move toward consensus definitions of both point-of-care musculoskeletal ultrasound (POC-MSKUS) and full diagnostic ultrasound, terminology to describe structures being assessed by ultrasound, and how these assessments should be interpreted.

Recent Advances in the Treatment of Hemophilia: A Review.

Progress in hemophilia therapy has been remarkable in the first 20 years of the third millennium, but the innovation began with the description the fractionation of plasma in 1946. The first concentrates followed the discovery of FVIII in the cryoprecipitate of frozen plasma and FIX in the supernatant in the early 1960s, which led to the initial attempts at replacement therapy. Unfortunately, the lack of screening methods for viral pathogens resulted in people with hemophilia (PWH) receiving concentrates contaminated by hepatitis A virus, hepatitis C virus, and human immunodeficiency virus, as these concentrates were made from large industrial pools of plasma derived from thousands of donors.

Iliopsoas hematoma in patients with COVID-19 on low-molecular-weight heparin treatment.

Patients with COVID-19 are at high risk of thromboembolic events; for this reason, the use of heparin is largely recommended but, in addition to thrombotic complications, bleeding is a significant cause of morbidity in patients with COVID-19. Idiopathic iliopsoas hematoma is a very rarely described hemorrhagic complication in patients with COVID-19. We report here two cases of iliopsoas hematoma in male patients with COVID-19 and being treated with heparin.