Real-World Data on Effectiveness and Safety of First-Line Use of Caplacizumab in Italian Centers for the Treatment of Thrombotic Thrombocytopenic Purpura: The Roscapli Study.

: Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy caused by the formation of anti-ADAMTS13 antibodies. Caplacizumab is approved for the treatment of acute episodes of iTTP in conjunction with plasma exchange (PEX) and immunosuppression. Real-world data for the use of caplacizumab in Italy have been recently published by a limited number of centers located in the northern and middle regions of the country only.

Effects of coagulation factors on bone cells and consequences of their absence in haemophilia a patients.

Haemophilia is associated with reduced bone mass and mineral density. Due to the rarity of the disease and the heterogeneity among the studies, the pathogenesis of bone loss is still under investigation. We studied the effects of coagulation factors on bone cells and characterized in a pilot study the osteoclastogenic potential of patients' osteoclast precursors.

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.

An integrated multitool analysis contributes elements to interpreting unclassified factor IX missense variants associated with hemophilia B.

Background: Dissection of genotype-phenotype relationships in hemophilia B (HB) is particularly relevant for challenging (mild HB) or for HB-associated but unclassified factor (F)IX missense variants.

Objective: To contribute elements to interpret unclassified HB-associated FIX missense variants by a multiple-level approach upon identification of a reported, but uncharacterized, FIX missense variant associated with mild HB.

Methods: Molecular modeling of wild-type and V92A FIX variants, expression studies in HEK293 cells with evaluation of protein (ELISA, western blotting) and activity (activated partial thromboplastin time-based/chromogenic assays) levels after recombinant expression, and multiple prediction tools.

Design organization and clinical processes around patient characteristics: Evidence from a multiple case study of Hemophilia.

There is growing evidence of the relevance of designing organization of care around patient characteristics; this is especially true in the case of complex chronic diseases. The goal of the paper - that focuses on the analysis of the clinical condition hemophilia in three different centers - is to address two different research questions:1. How can we define, within the same clinical condition, different patient profiles homogeneous in terms of intensity of service required (e.

The value-based healthcare approach to haemophilia: Development of outcome measures for the evaluation of care of people with haemophilia.

Introduction: Considering the advances in haemophilia management and treatment observed in the last decades, a new set of value-based outcome indicators is needed to assess the quality of care and the impact of these medical innovations.

Aim: The Value-Based Healthcare in Haemophilia project aimed to define a set of clinical outcome indicators (COIs) and patient-reported outcome indicators (PROIs) to assess quality of care in haemophilia in high-income countries with a value-based approach to inform and guide the decision-making process.

Methods: A Value-based healthcare approach based on the available literature, current guidelines and the involvement of a multidisciplinary group of experts was applied to generate a set of indicators to assess the quality of care of haemophilia.

Personalized Prophylaxis with myPKFiT: A Real-World Cost-Effectiveness Analysis in Haemophilia A Patients.

This study aimed to assess the effectiveness and costs associated with pharmacokinetics-driven (PK) prophylaxis based on the myPKFiT device in patients affected by hemophilia A (HA) in Italy. An observational retrospective study was conducted in three Italian hemophilia centers. All patients with moderate or severe HA, aged ≥ 18 years, capable of having PK estimated using the myPKFiT device, and who had had a clinical visit between 1 November 2019 and 31 March 2022 were included.

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).

Von Willebrand factor hyperactivity affects the outcome of lower limb revascularization in subjects with type 2 diabetes mellitus complicated by diabetic foot vasculopathy: An observational pilot study.

Unlabelled: Aim of this study is to evaluate any differences in VWF antigen, VWF activity and ADAMTS-13 activity before and after successful and non-successful Percutaneous Transluminal Angioplasty (PTA) in subjects with type 2 diabetes (T2DM) complicated by Chronic limb-threatening ischemia (CLTI) in diabetic foot vasculopathy.

Methods: In this prospective observational pilot study, we enrolled 35 T2DM subjects who underwent lower limb PTA. Transcutaneous oximetry was performed in all patients before and 6 weeks after PTA.

Awareness of individual goals, preferences, and priorities of persons with severe congenital haemophilia A for a tailored shared decision-making approach to liver-directed gene therapy. A practical guideline.

In clinical medicine, shared decision making (SDM) is a well-recognized strategy to enhance engagement of both patients and clinicians in medical decisions. The success of liver-directed gene therapy (GT) to transform severe congenital haemophilia A (HA) from an incurable to a curable disease has launched a shift beyond current standards of treatment. However, GT acceptance remains low in the community of HA persons.

Immune and Hereditary Thrombotic Thrombocytopenic Purpura: Can ADAMTS13 Deficiency Alone Explain the Different Clinical Phenotypes?

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by a hereditary or immune-mediated deficiency of the enzyme ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). TTPs are caused by the following pathophysiological mechanisms: (1) the presence of inhibitory autoantibodies against ADAMTS13; and (2) hereditary mutations of the gene, which is present on chromosome 9. In both syndromes, TTP results from a severe deficiency of ADAMTS13, which is responsible for the impaired proteolytic processing of high-molecular-weight von Willebrand factor (HMW-VWF) multimers, which avidly interact with platelets and subendothelial collagen and promote tissue and multiorgan ischemia.

Measurement of extended half-life recombinant FVIII molecules: and evidence of relevant assay discrepancies.

Background: Extended half-life recombinant FVIII products (EHL-rFVIIIs) have been engineered to improve the pharmacokinetic profile of FVIII, enabling better hemostatic protection with a reduced number of injections in persons with hemophilia. Previous studies showed several discrepancies in FVIII activity (FVIII:C) measurements for EHL-rFVIIIs comparing one-stage clotting assay (OSA) and chromogenic assay (CSA), although a systematic investigation of this phenomenon is still lacking.

Objective: Evaluation of the accuracy and precision of measurement of all available EHL-rFVIIIs with 5 different assays both and .

Mild and Moderate Hemophilia A: Neglected Conditions, Still with Unmet Needs.

Hemophilia A (HA) is an inherited X-linked bleeding disorder, caused by the deficiency of coagulation factor VIII (FVIII), with variable clinical phenotypes [...

Health Related Quality of Life and Psychopathological Symptoms in People with Hemophilia, Bloodborne Co-Infections and Comorbidities: An Italian Multicenter Observational Study.

Background: The health-related quality of life (HRQoL) of people with hemophilia (PWH) is an important issue, especially considering people suffering from chronic diseases beyond hemophilia. The principal aim of this study was to investigate the presence and relevance of psychological symptoms, both internalizing and externalizing, lifestyle, and HRQoL in a group of Italian PWH with chronic bloodborne co-infections and comorbidities. Furthermore, the research describes the association between psychological aspects and the impact of disease-related characteristics (type of hemophilia, presence of co-infections, and comorbidities) on them.

Feasibility, effectiveness, and safety of edoxaban administration through percutaneous endoscopic gastrostomy: 12-months follow up of the ORIGAMI study.

Background And Aims: Edoxaban proved to be safe and effective also in fragile patients, but its administration through percutaneous endoscopic gastrostomy (PEG) has not been previously investigated. The purpose of this study was to evaluate the feasibility and the preliminary safety and efficacy profiles of edoxaban administered PEG in patients with an indication for long-term oral anticoagulation.

Methods: ORIGAMI was a prospective, single-arm, observational study (NCT04271293).

Laying the foundations for gene therapy in Italy for patients with haemophilia A: A Delphi consensus study.

Introduction: Current treatment for haemophilia A involves factor VIII replacement or non-replacement (emicizumab) therapies, neither of which permanently normalise factor VIII levels. Gene therapy using adeno-associated viral (AAV) vectors is an emerging long-term treatment strategy for people with severe haemophilia A (PwSHA) that is likely to be available for clinical use in the near future.

Aim: This article proposes practical guidelines for the assessment, treatment, and follow-up of potential PwSHA candidates for AAV-based gene therapy.

Oral Squamous Cell Carcinoma-Associated Thrombosis: What Evidence?

Venous thromboembolism (VTE) disease is the second leading cause of mortality in cancer patients. In the general population, the annual incidence of a thromboembolic event is about 117 cases per 100,000 persons, but cancer increases this risk about fourfold, while in patients receiving chemotherapy and surgical treatment, it is about sevenfold. Oral squamous cell carcinoma (OSCC) is the most common form of oral cancer and represents a multistep process in which environmental factors and genetic alterations are implicated.

IDEAL study: A real-world assessment of pattern of use and clinical outcomes with recombinant coagulation factor IX albumin fusion protein (rIX-FP) in patients with haemophilia B in Italy.

Introduction: Factor IX replacement therapy is used for treatment and prophylaxis of bleeding in haemophilia B. rIX-FP is an extended half-life albumin-fusion protein, which, in clinical studies, has demonstrated prolonged dosing intervals up to 21 days for routine prophylaxis, providing therapeutic benefit.

Aims: To describe dosing frequency and consumption (primary endpoint), efficacy and safety of rIX-FP treatment during routine clinical practice in Italy.