We retrospectively analysed the data files of 171 adults and 87 children/adolescents with severe haemophilia, except for 14 patients (moderate / minor) (1), to develop a global population pharmacokinetic (PK) model for eight factors VIII (FVIII) that could estimate individual PK parameters for targeting the desired level of FVIII activity (FVIII:C)...
Published in Frontiers in Immunology
The development of an immune response against therapeutic factor VIII is the major complication in hemophilia A patients. Oligomannose carbohydrates at N239 and/or N2118 on factor VIII allow its binding to the macrophage mannose receptor expressed on human dendritic cells, thereby leading to factor VIII endocytosis and presentation to CD4+ T lympho...
Published in Frontiers in Immunology
Replacement therapy with coagulation factor VIII (FVIII) represents the current clinical treatment for patients affected by hemophilia A (HA). This treatment while effective is, however, hampered by the formation of antibodies which inhibit the activity of infused FVIII in up to 30% of treated patients. Immune tolerance induction (ITI) protocols, w...
Published in Frontiers in Immunology
Anti-drug antibodies to coagulation factor VIII (fVIII), often termed inhibitors, present the greatest economical and treatment related obstacle in the management of hemophilia A. Although several genetic and environmental risk factors associated with inhibitor development have been identified, the precise mechanisms responsible for the immune resp...
Published in Drug Design, Development and Therapy
Emicizumab is a bispecific, humanized, monoclonal antibody mimicking the factor (F) VIII cofactor activity in mediating the generation of FXa by FIXa in patients with hemophilia A (HA). This subcutaneous non-factor agent has been recently extensively approved for the prophylaxis of patients of HA patients with and without FVIII-inhibitors of all ag...
Published in Frontiers in Immunology
Therapeutic treatment of bleeds with FVIII can lead to an antibody response that effectively inhibits its function. Herein, we review the factors that contribute to this immunogenicity and possible ways to overcome it.
Published in Molecular Therapy. Methods & Clinical Development
Published in Frontiers in Immunology
Development of neutralizing antibodies against biotherapeutic agents administered to prevent or treat various clinical conditions is a longstanding and growing problem faced by patients, medical providers and pharmaceutical companies. The hemophilia A community has deep experience with attempting to manage such deleterious immune responses, as the ...
Published in Annals of Cardiac Anaesthesia
The association of Hemophilia A and ruptured aneurysm of sinus of valsalva (RSOV) has never been reported to the best of our knowledge. We report the case of a 29-year-old male patient with Hemophilia type A who presented with a RSOV into right atrium (RA). The patient underwent device closure off the RSOV and received Factor VIII infusions to decr...
Published in Haemophilia : the official journal of the World Federation of Hemophilia
Factor replacement therapy with factor VIII (FVIII) concentrates is the current standard of care for patients with haemophilia A. Postadministration monitoring of FVIII activity during on-demand or prophylactic treatment is important, for example to guide a suitable dosing regimen. While the use of two-stage chromogenic substrate (CS) assays is inc...
