It is recommended that each haemophilia centre should ensure that appropriate laboratory assays are available for FVIII and FIX products in local clinical use.
Integrating genomics, lifestyle and environmental data is expected to be key to: 1) identify which haemophilia patients are less likely to benefit from a given intervention; 2) define optimal dosing and scheduling of bypassing agents (or FVIII) to employ in combination with non-factor products; 3) establish tests to monitor in vivo thrombin generation; 4) improve communication and deliver results to individuals.
SUMMARY: Background We have previously demonstrated that von Willebrand factor (VWF) is essential in platelet-specific FVIII (2bF8) gene therapy of hemophilia A (HA) with inhibitory antibodies (inhibitors).
ClotChip T<sub>peak</sub> values correlate very well with ROTEM, TGA and FVIII assays, opening up possibilities for its use in personalized coagulation factor replacement therapy in haemophilia.
Further elucidation of the shared mechanisms underlying abnormal bone homeostasis in the absence of FVIII or FIX is needed to guide evidence-based approaches to the screening and treatment of the prevalent bone defects in hemophilia A and B.
Haemophilia is a serious inherited bleeding disorder resulting from a deficiency of coagulation factor VIII (haemophilia A) or coagulation factor IX (haemophilia B).
AHCDC: Association of Hemophilia Clinic Directors of Canada; AICE: Italian Association of Hemophilia Centres; ATHN: American Thrombosis and Hemostasis Network; EAHAD: European Association for Haemophilia and Allied Disorders; EHC: European Hemophilia Consortium; FIX: Coagulation Factor IX; FVIII: Coagulation Factor VIII; HAL: Haemophilia Activity List; HJHS: Haemophilia Joint Health Score; HTC: Hemophilia Treatment Centre; HTCCNC: Hemophilia Treatment Centre Collaborative Network of China; MASAC: Medical and Scientific Advisory Council; MDT: Multidisciplinary team; NHD: National Haemophilia Database; NHF: National Hemophilia Foundation; PK: Pharmacokinetics; POCUS: Point of care ultrasound; PWH: People with haemophilia; SHIELD: Supporting Hemophilia through International Education, Learning and Development; WFH: World Federation of Hemophilia.
Emicizumab, a bispecific humanized monoclonal antibody, bridges activated factor IX (FIX) and FX to restore the function of missing activated FVIII in hemophilia A. Emicizumab prophylaxis in children with hemophilia A and FVIII inhibitors was investigated in a phase 3 trial (HAVEN 2).
Here, we report a universal approach to correct the various mutations in HA patient iPSCs by the targeted insertion of the FVIII gene into the human H11 site via CRISPR/Cas9.
Encouraging clinical progresses have been also obtained from trials of gene therapy for haemophilia A. Transgene expression persisted for three years with circulating FVIII activity levels of 52.3% in patients treated with AAV vector containing a codon-optimized F8 cDNA.
The K coefficient was 0.91 when BIOPHEN™ FVIII:C was compared with the historical classification of the patients, demonstrating an optimal diagnostic accuracy in HA.
The current interest in recombinant factor VIII (rFVIII) products stems from the fact that they offer a technological solution to prolonging the half-life of and reducing the risk of formation of alloantibodies (inhibitors) against FVIII in treated patients with hemophilia A (HA).
Here, hemophilia A (factor VIII-deficient; FVIII-deficient) mice or TAFI-deficient mice with transient (antibody-induced) hemophilia A were used to determine the role of FVIII and TAFI in vascular remodeling after joint bleeding.
Health-related quality-of-life and treatment satisfaction of individuals with hemophilia A treated with turoctocog alfa pegol (N8-GP): a new recombinant extended half-life FVIII.
This scenario is further complicated in the presence of nucleotide changes associated with FVIII deficiency (Haemophilia A), which weaken the authentic 5'ss and create/strengthen cryptic 5'ss.