A factor VIII-deficient knockout mouse was used as a model for severe hemophilia A to characterize the immune response to recombinant human factor VIII (fVIII) and to study new approaches for induction of immune tolerance to fVIII. Mice initially received periodic injections of fVIII in doses similar to those used for the treatment of human hemophilia A. To induce immune tolerance, a hamster mo...

BACKGROUND Recombinant factor VIII (FVIII), used for haemophilia A therapy, is one of the most challenging among the therapeutic proteins produced in heterologous expression systems. Deletion variant of FVIII, in which the entire domain B is replaced by a short linker peptide, was approved for medical use. Efficacy and safety of this FVIII deletion variant are similar to full-length FVIII prepa...

When Factor VIII/von Willebrand factor (FVIII/vWF) protein is rechromatographed on 4% agarose in 0.25 M CaCl(2), the protein and vWF activity appear in the void volume, but most of the FVIII procoagulant activity elutes later. Recent evidence suggests that the delayed FVIII procoagulant activity is a proteolytically modified form of FVIII/vWF protein that filters anomalously from agarose in 0.2...

Hemophilia A in its severe form is a life-threatening hemorrhagic disease that is caused by mutations in the factor VIII (FVIII) gene (symbol F8). About 25% of patients who receive replacement therapy develop neutralizing antibodies that inhibit the function of substituted FVIII. Long-term application of high doses of FVIII has evolved as an effective therapy to eradicate the antibodies and to ...

Factor VIII (FVIII) functions as a cofactor within the intrinsic pathway of blood coagulation. Quantitative or qualitative deficiencies of FVIII result in the inherited bleeding disorder hemophilia A. Expression of FVIII (domain structure A1-A2-B-A3-C1-C2) in heterologous mammalian systems is 2 to 3 orders of magnitude less efficient compared with other proteins of similar size compromising rec...

Following replacement therapy with coagulation factor VIII (FVIII), up to 30 % of haemophilia A patients develop FVIII-specific inhibitory antibodies (FVIII inhibitors). Immune tolerance induction (ITI) is not always successful, resulting in a need for alternative treatments for FVIII inhibitor-positive patients. As tolerance induction in the course of ITI appears to involve the formation of an...

UNLABELLED ESSENTIALS: Anti-factor VIII (FVIII) inhibitory antibody formation is a severe complication in hemophilia A therapy. We genetically engineered and characterized a mouse model with complete deletion of the F8 coding region. F8(TKO) mice exhibit severe hemophilia, express no detectable F8 mRNA, and produce FVIII inhibitors. The defined background and lack of FVIII in F8(TKO) mice will ...

A significant proportion of hemophilia A patients receiving transfusions of factor VIII (FVIII) develop a specific antibody response towards FVIII. These antibodies are usually detected by assays in which they inhibit the function of the molecule, such as the Bethesda clotting test. We have prepared anti-FVIII antibodies by specific immunoadsorption from the plasma of four hemophiliacs with sta...

BACKGROUND AND PURPOSE Despite clear roles of factor VIII (FVIII) and von Willebrand factor (vWF) in thrombosis, few studies have examined the relationship of these factors with acute ischemic stroke (AIS). We sought to determine whether concurrent elevation in FVIII and vWF was associated with adverse events and outcomes. METHODS From our prospective stroke registry, patients consecutively a...

Coagulation factor VIII (FVIII) inhibitors are the most severe complications of haemophilia A treatment. We studied the effect of a non-activated prothrombin concentrate (PCC) combined with FVIII in vitro. FVIII antibodies minimised the in vitro thrombin generation of standard human plasma and prolonged the lag phase at a residual FVIII activity of ≤ 0.01 IU/ml. Time to clotting of FVIII-inhibi...