The primary cellular source of factor VIII (FVIII) biosynthesis is controversial, with contradictory evidence supporting an endothelial or hepatocyte origin. LMAN1 is a cargo receptor in the early secretory pathway that is responsible for the efficient secretion of factor V (FV) and FVIII to the plasma. Lman1 mutations result in combined deficiency of FV and FVIII, with levels of both factors r...

We have investigated the periodic acid Schiff (PAS) Coomassie staining ratio of the human factor VIII/von Willebrand factor (fVIII/vWf) protein. The PAS-Coomassie staining ratio is consistent over 8 days. The PAS-Coomassie ratio of fVIII/vWf protein purified from different starting materials does not appear to be significantly different. The PAS stain can detect as little as 300 ng of carbohydr...

introduction: haemophilia a is the most common inherited x-linked recessive bleeding disorder. the severity of the resultant bleeding diathesis depends on the fviii levels associated with the mutation. analysis of carrier state can be made indirectly by dna linkage analysis or directly by identifying the mutation that leads to the disease. the aim of this study was to identification of the caus...

Human factor VIII(FVIII) inhibitors are pathologic, circulating antibodies that inactivate FVIII. We have examined the location of epitopes on the FVIII protein for inhibitors from hemophilia A and nonhemophilic individuals. The inhibitors were of type I or type II in the kinetics of their inactivation of FVIII. A cDNA clone of human FVIII was used to express defined FVIII protein fragments in ...

The stability of activated human and porcine factor VIII (fVIII) differ, but a direct comparison of their structural and functional properties has not been made. Highly purified, heterodimeric human recombinant and porcine plasma-derived fVIII were exchanged into a common buffer and some minor contaminants were removed by anion-exchange chromatography. The activations of human and porcine fVIII...

High-capacity adenoviral (HC-Ad) vectors expressing B-domain-deleted human or canine factor VIII from different liver-specific promoters were evaluated for gene therapy of hemophilia A. Intravenous administration of these vectors into hemophilic FVIII-deficient immunodeficient SCID mice (FVIIIKO-SCID) at a dose of 5 x 10(9) infectious units (IU) resulted in efficient hepatic gene delivery and l...

Cryo-electron microscopy (Cryo-EM)(1) is a powerful approach to investigate the functional structure of proteins and complexes in a hydrated state and membrane environment(2). Coagulation Factor VIII (FVIII)(3) is a multi-domain blood plasma glycoprotein. Defect or deficiency of FVIII is the cause for Hemophilia type A - a severe bleeding disorder. Upon proteolytic activation, FVIII binds to th...

We report a case of patient with recurrent hematomas while on anticoagulation for pulmonary embolism and prolonged hospital stay due to delayed diagnosis acquired hemophilia A. Acquired A is rare autoimmune bleeding disorder autoantibodies directed against coagulation factor VIII (FVIII), leading an FVIII deficiency. isolated activated partial thromboplastin time (aPTT) in warrants workup This ...

OBJECTIVE Both soluble endothelial protein C receptor (sEPCR) and factor VIII (FVIII) seem to be potential mediators in thrombotic and inflammatory states. The aim of the present study was to determine the relation between plasma sEPCR and FVIII levels in a group of healthy Turkish infants. METHODS The study population consisted of 50 healthy infants aged 6 months (Group 1, n=23) and 12 month...