A Novel Murine Model Enabling rAAV8-PC Gene Therapy for Severe Protein C Deficiency.

Severe protein C deficiency (SPCD) is a rare inherited thrombotic disease associated with high morbidity and mortality. In the current study, we established a viable murine model of SPCD, enabling preclinical gene therapy studies. By creating SPCD mice with severe hemophilia A (PROC/F8), the multi-month survival of SPCD mice enabled the exploration of recombinant adeno-associated viral vector-PC (rAAV8-PC) gene therapy (GT).

Pediatric splenic infarction: Assessment of associated clinical conditions and outcome.

Pediatric splenic infarction (SI) is rare yet clinically significant. Publications regarding this complication are mostly limited to case reports. This is a retrospective study examining SI etiology, clinical presentation, management, and outcomes among children.

Bleeding phenotype and hemostatic evaluation by thrombin generation in children with Noonan syndrome: A prospective study.

Background: This study aimed to evaluate the bleeding phenotype and to conduct a comprehensive hemostatic evaluation in individuals with Noonan syndrome (NS), a dominantly inherited disorder caused by pathogenic variants in genes associated with the Ras/MAPK signaling pathway.

Methods: Children with a genetically confirmed diagnosis of NS underwent clinical evaluation, routine laboratory tests, platelet function testing, and thrombin generation (TG) assessment.

Results: The study included 24 children.

Management of surgery in persons with hemophilia A receiving emicizumab prophylaxis: data from a national hemophilia treatment center.

Background: Persons with hemophilia A may require surgical procedures. Real-world data on invasive procedures in persons with hemophilia A receiving emicizumab prophylaxis are limited.

Objectives: To evaluate the safety of invasive procedures in persons with hemophilia A receiving emicizumab prophylaxis and their outcomes in a longitudinally followed cohort.

Factor VIII inhibitors in hemophilia A treated with emicizumab: longitudinal follow-up of outcomes.

Background: Using emicizumab in lieu of immune tolerance induction (ITI) for patients with hemophilia A (HA) and factor (F)VIII inhibitors has been well described. However, decisions regarding ITI initiation, regimen, and preservation of tolerance remain to be elucidated.

Objectives: To study the course of FVIII inhibitors in patients with HA and a history of FVIII inhibitors receiving emicizumab prophylaxis.

[NEW INNOVATIONS IN THE TREATMENT OF HEMOPHILIA].

Hemophilia is a congenital bleeding disorder with a deficiency of coagulation factor 8 or 9 (hemophilia A or B, respectively) and a tendency for recurrent bleeding, especially into muscles and joints, which may cause orthopedic damage and necessitate joint replacement surgeries at a young age. In recent years, there has been a huge breakthrough in the treatment of hemophilia. Until recently, the only available therapy was based on repeated intravenous injection of factor concentrates (replacement therapy).

Association between Thrombin Generation and Clinical Characteristics in COVID-19 Patients.

Introduction: Coronavirus disease 2019 (COVID-19) disease is associated with coagulopathy and an increased risk of thrombosis. An association between thrombin generation (TG) capacity, disease severity, and outcomes has not been well described.

Methods: We assessed the correlation of TG with sequential organ failure assessment (SOFA) and sepsis-induced coagulopathy (SIC) scores and clinical outcomes by analysis of plasma samples obtained from hospitalized COVID-19 patients.

Application of a clinical decision rule and laboratory assays in pediatrics: Adult heparin-induced thrombocytopenia.

Background: Heparin-induced thrombocytopenia (HIT) is rare among pediatric patients. The diagnosis of HIT depends upon clinical decision tools to assess its pretest probability, supported by laboratory evidence of anti-platelet factor 4 (anti-PF4)/heparin antibodies.

Aims: To compare the use of the 4Ts score clinical decision tool, clinical characteristics, and laboratory findings between pediatric and adult patients with suspected HIT.

Anti-TFPI for hemostasis induction in patients with rare bleeding disorders, an ex vivo thrombin generation (TG) guided pilot study.

Background: Rare bleeding disorders (RBD) are inherited coagulopathies, whose hemostatic control is based upon replacement therapy. Marstacimab (PF-06741086) is a human monoclonal IgG that targets the Kunitz2 domain of tissue factor pathway inhibitor [TFPI]. Marstacimab is currently in development for bleeding prophylaxis in patients with hemophilia.

Pediatric severe factor XI deficiency: A multicenter study.

Background: Factor XI (FXI) deficiency is a rare autosomal recessive bleeding disorder. Only scarce publications address its clinical features in children. The increased prevalence of FXI deficiency in Israel enabled data collection for this large multicenter cohort study.

Real-World Data on Bleeding Patterns of Hemophilia A Patients Treated with Emicizumab.

Emicizumab (Hemlibra™) is approved for prophylaxis of hemophilia A (HA) patients. The HAVEN studies addressed bleeding reduction in emicizumab-treated patients, but real-world data on bleeding patterns during emicizumab therapy are lacking. We aimed to compare the occurrence of breakthrough bleeding at different time points, starting from emicizumab initiation.

Emicizumab prophylaxis: Prospective longitudinal real-world follow-up and monitoring.

Introduction: Real-world data on prophylaxis of severe haemophilia A (HA) patients treated by emicizumab are scarce.

Aim: To study the efficacy and safety of longitudinal emicizumab prophylaxis and assess laboratory monitoring correlations in a large patient cohort.

Methods: HA patients with and without FVIII inhibitors, initiating emicizumab prophylaxis, were prospectively enrolled.

Emicizumab prophylaxis in haemophilia patients older than 50 years with cardiovascular risk factors: Real-world data.

Introduction: Emicizumab (Hemlibra™) is approved for prophylaxis of Haemophilia A (HA) patients with and without inhibitors. However, real-world data on emicizumab use in the elderly HA patients with concomitant cardiovascular risk factors are lacking.

Aim: To evaluate the safety and efficacy of emicizumab in a real-world cohort of elderly HA patients.

Emicizumab treatment and monitoring in a paediatric cohort: real-world data.

Real-world data on emicizumab use and monitoring in paediatric severe haemophilia A (HA) patients are scarce. We therefore sought to evaluate safety, efficacy, and laboratory monitoring of emicizumab prophylaxis in a cohort of 40 children with severe HA, including 22 non-inhibitor patients and nine infants younger than one year. Bleeding, trauma, adverse events, and surgeries were documented during a median follow-up of 45 weeks.

Allergy and inhibitors in hemophilia - a rare complication with potential novel solutions.

Introduction: Hemophilia is a rare bleeding disorder caused by a deficiency of the plasma coagulation factors VIII and IX (hemophilia A [HA] and hemophilia B [HB], respectively). Replacement therapy with clotting factor concentrates is the mainstay of treatment. Unlike in patients with HB, anaphylaxis in patients with HA is extremely rare.

[HEMOPHILIA - A ROYAL DISEASE IN THE HOLY LAND].

Introduction: Hemophilia is a hereditary congenital hemorrhagic diathesis caused by mutations in blood coagulation factor VIII (FVIII) or IX (FIX) genes, causing hemophilia A and B, respectively. Most cases are familial but a significant minority is sporadic.

Objectives: To examine the presenting symptoms of patients with hemophilia in Israel and identify causes for delay in diagnosis.

Subcutaneous Injection of Tranexamic Acid to Reduce Bleeding During Dermatologic Surgery: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial.

Background: Topical application, oral, and IV injection of tranexamic acid (TXA) have been used to reduce surgical bleeding.

Objective: To evaluate the safety and efficacy of TXA injected subcutaneously to reduce bleeding during dermatologic surgery.

Methods: In this double-blinded, placebo-controlled, randomized prospective study, 131 patients were randomized to subcutaneous injection of lidocaine 2% diluted 1:1 with either saline (placebo) or TXA 100 mg/1 mL before surgery.

Combination of hemostatic therapies for treatment of patients with hemophilia A and inhibitors.

Background: Therapy application and monitoring of patients with hemophilia A (HA) and inhibitors are challenging. In the current study, combined FVIII - bypass therapy was implemented for a cohort of severe HA patients with inhibitors.

Methods: Plasma of 15 HA patients with inhibitors was spiked ex vivo with FVIII, rFVIIa, FEIBA and their combinations and thrombin generation (TG) was studied.

The hemostatic efficacy of chitosan-pads in hemodialysis patients with significant bleeding tendency.

Background: Patients on chronic hemodialysis often have acquired coagulopathy that can aggravate bleeding from puncture site after needle extraction. Chitosan-based pads have been reported to accelerate hemostasis even in the presence of coagulopathy. The aim of this study was to evaluate the hemostatic efficacy of the chitosan pads compared to gauze pads, applied for local hemostasis.