It has been established that low-density lipoprotein receptor-related protein (LRP) is involved in the cellular uptake and degradation of coagulation factor VIII (FVIII) in vitro. To address the physiologic role of LRP in regulating plasma FVIII in vivo, we used cre/loxP–mediated conditional LRPdeficient mice (MX1cre LRPflox/flox). Upon inactivation of the LRP gene, MX1cre LRPflox/flox mice had...

Factor VIII (FVIII) inhibitor antibodies are classified into 2 groups according to the kinetic pattern of FVIII inactivation. Type 2 antibodies are more commonly observed in patients with acquired hemophilia A and do not completely inhibit FVIII activity; in most cases, substantial levels of circulating FVIII are detected. Three type 2 autoantibodies from patients who had normal levels of FVIII...

Coagulation factor VIII (FVIII), von Willebrand factor (VWF), and ADAMTS13 play an important role in regulation of normal hemostasis. However, little is known about their roles in patients with malignancy, particularly with cutaneous melanoma. Whole genome sequencing data are available for 25,719 cases in 126 cancer genomic studies for analysis. All sequencing data and corresponding pathology f...

BACKGROUND AND OBJECTIVES Difficulties in identifying the coexistence of neutralizing anti-factor VIII antibodies (anti-fVIII) and lupus anticoagulant (LA) are mainly due to the interference of LA on anti-fVIII assays. Our aim was to reveal the presence of anti-fVIII using a system that is not affected by LA. DESIGN AND METHODS We developed an enzyme-linked immunosorbent assay (ELISA) method ...

Factor VIII (FVIII) is a key protein in blood coagulation, deficiency or malfunction of which causes Haemophilia A. The sole cure for this condition is intravenous administration of FVIII, whose membrane-bound structure we have studied by Cryo-electron microscopy and image analysis. Self-assembled lipid nanotubes were optimised to bind FVIII at close to native conditions. The tubes diameter was...

Factor VIII (FVIII) inhibitor antibodies are classified into 2 groups according to the kinetic pattern of FVIII inactivation. Type 2 antibodies are more commonly observed in patients with acquired hemophilia A and do not completely inhibit FVIII activity; in most cases, substantial levels of circulating FVIII are detected. Three type 2 autoantibodies from patients who had normal levels of FVIII...

BACKGROUND AND OBJECTIVES The development of neutralizing anti-factor VIII antibodies (a-fVIII) is a major clinical complication. Lupus anticoagulant (LA) might affect detection of a-fVIII, since both inhibitors may act on the same coagulation pathway. Our aim was to accomplish unequivocal detection and titration of a-fVIII even in the presence of LA. DESIGN AND METHODS We evaluated a-fVIII a...

Cryoprecipitate is the principal type of factor VIII (FVIII) concentrate used for treating haemophilia A in Tunisia. Allergic reactions, viral transmission, and inhibitor formation remain the most serious complications of FVIII therapy. The aims of the study presented here were to evaluate the efficacy of FVIII therapy, to investigate the inhibitor prevalence, and the factors which may affect i...

Neutralizing antibody formation against transgene products can represent a major complication following gene therapy with treatment of genetic diseases, such as hemophilia A. Although successful approaches have been developed to prevent the formation of anti-factor VIII (FVIII) antibodies, innovative strategies to overcome pre-existing anti-FVIII immune responses in FVIII-primed subjects are st...

OBJECTIVE Recent studies have demonstrated that galectin-1 (Gal-1) and galectin-3 (Gal-3) can bind von Willebrand factor and directly modulate von Willebrand factor-dependent early thrombus formation in vivo. Because the glycans expressed on human factor VIII (FVIII) are similar to those of von Willebrand factor, we investigated whether galectins might also bind and modulate the activity of FVI...