Abstract Hemophilia A is an X-linked bleeding disorder resulting in events due to insufficient levels of factor VIII (FVIII). The most significant complication the management hemophilia formation polyclonal neutralizing IgG (i.e., inhibitors) which impede FVIII procoagulant activity. In a (FVIII KO) murine model injected with multiple doses FVIII, FVIII-specific IgM were found persist despite e...

Abstract Deficiency of the procoagulant protein factor VIII (FVIII) is defining characteristic for individuals with inherited X-linked bleeding disorder hemophilia A. These require intravenous infusions FVIII to treat events, however ~30% develop neutralizing alloantibodies (i.e., inhibitors) against exogenous FVIII. Transcriptome analysis FVIII-stimulated peripheral blood mononuclear cells in ...

Factor VIII belongs to the coagulation cascade and is expressed as a long pre-protein (mature form, 2351 amino acids long). FVIII deficient or defective in hemophilic A patients, who need be treated with hemoderivatives recombinant substitutes, i.e., biologic drugs. The interaction between von Willebrand factor (VWF) influences pharmacokinetics of medications. In vivo, full-length (FL-FVIII) se...

Background and Aims: Hemophilia is a rare autoimmune disorder caused by autoantibodies directed in the majority of the cases against clotting factor VIII (FVIII). FVIII is extracted from human plasma or engineered from mammalian cell cultures using recombinant DNA technology. In Iran, most of the used FVIII is prepared from human plasma in Iranian Blood Transfusion Organization. It was seen imp...

Processing by the proprotein convertase furin is believed to be critical for the biological activity of multiple proteins involved in hemostasis, including coagulation factor VIII (FVIII). This belief prompted the retention of the furin recognition motif (amino acids 1645-1648) in the design of B-domain-deleted FVIII (FVIII-BDD) products in current clinical use and in the drug development pipel...

Anti-Factor VIII (FVIII) antibodies were prepared by a combination of salt precipitation, gel filtration chromatography, and specific adsorption over insolubilized FVIII from the serum of 10 healthy subjects with normal levels of FVIII. Antibody specificity was confirmed by the capacity to recognize soluble and insolubilized FVIII and to neutralize FVIII cofactor activity in FX activation. Epit...

Factor VIII (FVIII) functions as a cofactor for factor IXa in the contact coagulation pathway and circulates in a protective complex with von Willebrand factor (VWF). Plasma FVIII activity is strongly influenced by environmental and genetic factors through VWF-dependent and -independent mechanisms. Single nucleotide polymorphisms (SNPs) of the coding and promoter sequence in the FVIII gene have...

The mechanisms responsible for the low factor VIII (fVIII) activity in the plasma of patients with mild/moderate hemophilia A are poorly understood. In such patients, we have identified a series of fVIII mutations (Ile2098Ser, Ser2119Tyr, Asn2129Ser, Arg2150His, and Pro2153Gln) clustered in the C1 domain and associated with reduced binding of fVIII to von Willebrand factor (vWf). For each patie...

A main complication of treatment of patients with hemophilia A is the development of anti-factor VIII (fVIII) antibodies. The immunogenicity of fVIII potentially is a function of its procoagulant activity, which may result in danger signals that drive the immune response. Alternatively, intrinsic structural elements in fVIII may be particularly immunogenic. Finally, VWF, the carrier protein for...

To study the interaction of human factor VIII (FVIII) with its various ligands, select regions of cDNA encoding FVIII light chain were cloned into the plasmid expression vector pET3B to overproduce FVIII protein fragments in the bacterium Escherichia coli. Partially purified FVIII protein fragments were used to produce monoclonal antibodies. One monoclonal antibody, 60-B, bound both an FVIII pr...