We have developed a retroviral-vector system for the transfer and expression of a cloned blood clotting factor VIII cDNA. Since inclusion of the complete cDNA into existing vectors is precluded by its large size, we deleted most codons for the B-domain, which is also excised during in vivo maturation of factor VIII. When inserted into the retroviral vector M5-neoR (Laker, C., Stocking, C., Berg...

In this issue of Blood, Sanders and coworkers define the pathophysiology of types 1, 2, and 3 von Willebrand disease (VWD) in the Willebrand in the Netherlands (WiN) study by using the ratios of von Willebrand factor propeptide (VWFpp) or factor VIII activity to VWF antigen.

A simple technique using an aggregometer and fixed washed human platelets (FWP) and fibrillar collagen has been used to evaluate the contribution of the two components of the factor VIII (FVIII) complex to platelet-collagen interactions. FWP bound individually to collagen fibrils in suspension, and both the total number of FWP bound and the rate of adhesion increased with increasing collagen co...

Platelet function, factor VIII, fibrinogen levels, and fibrinolysis were studied in Europeans and in two groups of Nigerians living in Zaria, northern Nigeria, in order to see whether differences could help to explain the low incidence of atheroma and thrombosis in Nigerians. We confirmed the relative thrombocytopenia and observed a rapid disaggregation after ADP-induced platelet aggregation in...

Blood coagulation factors V and VIII each serve cofactor functions with different vitamin K-dependent serine proteases of the coagulation cascade. Physical, physiologic, and kinetic data suggest analogous structures and functions for these two proteins. Proteolytically activated factor V (factor Va) is required for the efficient production of thrombin from prothrombin by factor Xa. Similarly, a...

There is now convincing evidence that a high level of coagulation factor VIII is an important risk factor for venous thromboembolism. A factor VIII plasma concentration above 1500 IU/l is associated with an almost 5-fold risk for a first episode of venous thrombosis. In thrombosis patients high factor VIII has been shown to persist over time and is not related to an acute phase reaction. High f...

Cerebral venous thrombosis (CVT) rarely recurs, and the factors associated with a recurrence remain unclear. Recently, however, elevated plasma coagulation factor VIII has been considered a factor related to recurrent venous thromboembolism. Here we report a patient who had recurrent CVT associated with significantly elevated levels of factor VIII despite the chronic use of an antiplatelet agen...

Investigations were undertaken of the chemical nature and kinetics of interaction of three acquired inhibitors of Factor VIII. The inhibition was stoichiometric, one molecule of inhibitor (or one site on a molecule) being required to inactivate one molecule of Factor VIII. All three inhibitors were found to be monotypic antibodies of class IgG, Type K (gamma(2) kappa(2)). This appears to be the...

Rabbits were injected with an immunoglobulin fraction of human serum containing a factor VIII antibody. Factor VIII levels fell abruptly, persisted below 10% of a rabbit plasma standard for 12 hr. and returned to normal by 120-168 hr. The factor VIII antigen-antibody reaction did not result in Intravascular clotting as evaluated by kinetic studies with 125l-fibrinogen. However. small falls in f...