Deciphering the circulating microRNA signature of hemophilic arthropathy.

Background: Haemophilic arthropathy (HArt) is a serious complication in patients with hemophilia. Early diagnosis and treatment are essential to minimise the development of HArt. The use of biomarkers may improve early diagnosis of HArt.

Liver health in hemophilia in the era of gene therapy.

Gene therapy for hemophilia is a groundbreaking treatment approach with promising results and potential to reduce the burden of the disease. However, uncertainties remain, particularly regarding the liver side effects of AAV gene therapy, which are more common in hemophilia A. Unlike some other diseases, such as spinal muscular atrophy, where the target cell for gene therapy is different from the one affected by side effects, hemophilia gene therapy operates within the same cellular domain-the hepatocyte.

Relationship between plasma tissue Factor Pathway Inhibitor (TFPI) levels, thrombin generation and clinical risk of bleeding in patients with severe haemophilia A or B.

Introduction: Bleeding severity in severe haemophilic patients, with low thrombin generation (TG) capacity, can vary widely between patients, possibly reflecting differences in tissue factor pathway inhibitor (TFPI) level.

Aim: To compare free TFPI (fTFPI) levels in patients with severe haemophilia A (sHA) and severe haemophilia B (sHB) and to investigate in these patients as a whole the relationships between bleeding and TG potential, between TG potential and fTFPI level and between fTFPI level and bleeding tendency.

Methods: Data on bleeding episodes retrospectively recorded during follow-up visits over 5-10 years were collected and used to calculate the annualised joint bleeding rate (AJBR).

Multicenter evaluation of the hemostatic activity of emicizumab in patients with severe hemophilia A.

Background: Emicizumab has been approved for the prophylaxis of patients with hemophilia A with or without inhibitors. However, spontaneous and trauma-induced breakthrough bleeds have been reported in patients on emicizumab prophylaxis, and no laboratory assay has been validated to evaluate the hemostatic activity of emicizumab.

Objectives: The thrombin generation assay (TGA) could be a surrogate marker of the hemostatic efficacy of emicizumab.

Whole F8 gene sequencing identified pathogenic structural variants in the remaining unsolved patients with severe hemophilia A.

Background: No F8 genetic abnormality is detected in approximately 1% to 2% of patients with severe hemophilia A (HA) using conventional genetic approaches. In these patients, deep intronic variation or F8 disrupting genomic rearrangement could be causal.

Objectives: The study aimed to identify the causal variation in families with a history of severe HA for whom genetic investigations failed.

Stromal cell-derived factor 1 alpha (SDF-1alfa) and cartilage oligomeric matrix protein (COMP): Two potential signature biomarkers of radiological detectable hemophilic arthropathy.

Introduction: Hemophilia is a rare constitutional bleeding disorder due to a deficiency in Factor VIII or Factor IX. Recurrent hemarthroses, one of the major complications of the disease, lead to hemophilic arthropathy, a disabling condition that requires early diagnosis. Traditionally, clinical examination and plain film radiography have been used to diagnose hemophilic arthropathy.

Comparison of one-stage and chromogenic factor VIII assays to tailor the dose of recombinant factor VIII-Fc fusion protein (rFVIIIFc, efmoroctocog alfa) in adult patients with haemophilia A: Single-centre, real-world experience of surgery.

Background: Efmoroctocog alfa (rFVIIIFc) is an extended half-life FVIII used notably in surgery for patients with haemophilia A. More information is needed of its usage in real-life.

Methods: Adult patients with HA followed at the Lyon Comprehensive Hemophilia Care Center who underwent a surgery with rFVIIIFc were included in this retrospective analysis.

A single-centre experience of 29 total ankle replacement in haemophiliac patients: Therapeutic management, factor consumption and cost.

Introduction: In patients with haemophilia, repeated bleeding in large joints leads to chronic haemophilic arthropathy, a rare disease that can be managed surgically with ankle arthrodesis or with total ankle replacement (TAR). TAR has been reported to provide good surgical results in the medium/long-term and allow preservation of joint mobility but the medical therapeutic management of the patients has not been described.

Aim: To describe the medical therapeutic management of TAR.

Perspectives and perception of haemophilia gene therapy by French patients.

Introduction And Aim: A national survey was initiated by representatives of French patients with haemophilia (AFH) and the French reference centre for haemophilia, in order to appreciate the awareness and knowledge of these patients regarding haemophilia gene therapy (HGT) and understand better their position about this innovative treatment that will soon become available.

Results: Of 143 answers received, 137 could be analysed, representing about 3.5% of patients with severe or moderate haemophilia over 16year-old.

Occupational integration of adults with severe haemophilia (INTHEMO): A study based on the FranceCoag registry.

Introduction: Health of people with severe haemophilia (PwSH) improves thanks to the advancements in haemophilia care, giving them more opportunities in occupational integration. However, there is little literature on the occupational integration of PwSH.

Objectives: The main objective of our study was to assess the occupational integration of PwSH and to compare it with that of the general population.

Report of surgeries, their outcome and the thrombin generation assay in patients with Factor XI deficiency: A retrospective single-centre study.

Background: In patients with FXI deficiency, the risk of surgery-related bleeding is poorly correlated with plasma FXI activity (FXI:C); the latter can therefore not be used as a reliable predictor of bleeding in surgeries.

Objectives: The aim of this retrospective study was to determine whether thrombin generation assay (TGA) could be used to evaluate the risk of surgery-related bleeding in FXI-deficient patients. TGA parameters were compared to FXI:C values, haemostatic treatments and surgical outcomes.

Haemophilia A patients' medication adherence to prophylaxis with efmoroctocog alfa.

Introduction: Lightening the injection burden is commonly believed to improve prophylaxis adherence. Efmoroctocog alfa (rFVIIIFc) is the first recombinant FVIII-Fc fusion protein available in France. This clotting factor with an extended half-life could thus improve medication adherence.

Identification of new F8 deep intronic variations in patients with haemophilia A.

Introduction: With current molecular diagnosis, about 1 to 5% of haemophilia A (HA) patients remain genetically unresolved. In these cases, deep intronic variation or structural variation disrupting the F8 gene could be causal.

Aim: To identify the causal variation in four genetically unresolved mild-to-severe HA patients using an F8 mRNA analysis approach.

Evolution of clotting factor concentrates prescriptions and impact of recommendations of prophylaxis in children with haemophilia.

Prophylaxis treatment is considered as the reference approach for children with severe haemophilia A or B. However, no consensus about the best prophylaxis protocol has yet been identified in term of dosage and timing of infusions. Guidelines were drawn up in France in the early 2000s by an expert group.

A new paradigm for personalized prophylaxis for patients with severe haemophilia A.

Aim: For patients with severe haemophilia A, guidelines recommend prophylactic treatment with FVIII, with dose calculations targeting a predetermined FVIII trough level. However, this pharmacokinetic (PK) approach is suboptimal, with some patients experiencing breakthrough bleeds. We aimed to improve FVIII dosing by incorporating the thrombin generation assay, a global haemostasis assay whose main pharmacodynamic (PD) parameter, endogenous thrombin potential (ETP), predicts spontaneous bleeding risk.

A novel protocol for accurate and reliable postoperative bolus administration of recombinant factor VIIa using an automated mini-pump system.

Introduction: Recombinant FVIIa (rFVIIa) is widely used to manage bleeding risk during and after surgery in patients with haemophilia complicated by inhibitors. In the postoperative period, rFVIIa must be delivered frequently and regularly to maintain haemostasis, considering its short half-life. Preparation and manual administration of bolus doses of rFVIIa at regular intervals may place a strain on available nursing resources.

A Prolonged Treatment Response in Acquired Von Willebrand Syndrome.

Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder. We report herein a case of AVWS due to a monoclonal gammopathy of undetermined significance, in which a transient but prolonged response to a treatment by intravenous immunoglobulin (IVIG) was observed. The diagnosis was fortuitously made in a preoperative setting for neurosurgery, after biological exploration of an isolated prolonged activated partial thromboplastin time.