Factor VIII (antihemophilic factor) has been purified approximately 500.fold from the cryoprecipitate fraction of human plasma. The isolation procedure involves adsorption of contaminants with Al(OH),, column chromatography on tricalcium citrate-cellulose, precipitation with concanavalin A, and an agarose gel filtration step. The linal product is homogeneous when examined by zone electrophoresi...

Normal human plasma contains a complex of two proteins that are important in hemostasis and coagulation. The factor VIII procoagulant protein (antihemophilic factor) and the factor VIII-related protein (von Willebrand factor) are under separate genetic control, have distinct biochemical properties, and have unique and essential physiologic properties. While the nature of their interaction and t...

A chromogenic factor IX assay is developed which requires only two timedependent steps. Diluted plasma is mixed with a reagent containing factors VIII and X. The reaction is started by addition of a reagent containing factor XI", thrombin, CaCl2, and phospholipids. Then factor XIu activates factor IX if present, thrombin activates factor VIII, and subsequently the complete factor X activating c...

Von Willebrand disease is a common autosomal inherited bleeding disorder caused by quantitative or qualitative defects of von Willebrand factor, a multi-adhesive protein that binds platelets to exposed subendothelium and carries factor VIII in circulation. As a result of von Willebrand factor deficiency or abnormality, levels of factor VIII, the protein deficient in hemophilia A, may be variabl...

Two hemophilic beagles were given normal sibling. During observation 1200 A whole-body irradiation followed periods of 7 and 24 mo, there was no by a successful marrow graft from a evidence of factor VIII synthesis. ORTHOTOPIC TRANSPLANTATION of a normal liver into a hemophilic dog results in complete correction of the deficiency of factor VIII.”3 However, there are significant extrahepatic sou...

Therapeutic effectiveness of factor VIII inhibitor bypassing materials has been evaluated in dogs with hemophilia A. A standardized template gingival biopsy was performed using local anesthesia. Hemophilic dogs bled extensively from the biopsy site, whereas in normal dogs the wound was sealed within 5 + /- 2 min. If untreated, the hemophilic dogs frequently bled for several days. Factor VIII in...

Hemophilia A is caused by defects in the factor VIII gene. This results in life-threatening hemorrhages and severe arthropathies. Today, hemophiliacs are treated with human blood-derived factor VIII. In the future, it may be possible to use gene therapy to avoid long-term complications of conventional therapy and to improve the quality of life. However, initial gene therapy models using retrovi...

We have studied the modifications in the multimeric composition of plasma factor VIII/von Willebrand factor and the bleeding time response following administration of 1-Deamino-[8-D-arginine]-Vasopressin (DDAVP) to patients with different subtypes of von Willebrand's disease. In type I, all multimers were present in plasma in the resting state, though they were decreased in concentration. Admin...

The possible role of Ca2+ as an essential constituent part of the human factor VIII complex has been investigated by stability studies, metal determinations, and gel filtration experiments. In citrated plasma, the factor VIII coagulant activity (VIII:C) deteriorated during storage in a biphasic manner. Collection of blood in heparin, instead of chelating anticoagulants, or neutralization of cit...

Removal of blood-based additives from recombinant clotting factor concentrates continues to be advocated by the hemophilia community due to the history of infectious disease transmission with previous blood-derived clotting factor concentrates. In 2003, octocog-alpha, antihemophilic factor (recombinant), plasma/albumin-free method (ADVATE) was introduced, providing the first third-generation re...