Biosynthesis and Assembly of the Factor VIII-Von Willebrand Factor Complex

Both factor VIII and the von Willebrand factor (vWF) serve an essential role in the hemostatic proces; factor VIII functions as a cofactor in the intrinsic coagulation pathway (van Dieijen et al. 1981; Mertens et al. 1985) whereas vWF is hemostatically important in the mediation of platelet-vessel wall interactions at sites of vascular injury (Tschopp et al. 1974; Sakariassen et al. 1979). In blood factor VIII and vWF are not present as distinct proteins but rather circulate as non-covalently linked complexes. Several lines of evidence indicate that this phenomenon is of physiological significance. For instance, it now seems clear that vWF functions as a carrier protein and as such has a stabilizing effect on factor VIII. This view stems from the observation that reduced or absent synthesis of vWF (as seen in von Willebrand’s disease) is accompanied with markedly reduced concentrations of plasma factor VIII (Ruggeri and Zimmerman 1987). Similarly, a rise in vWF concentration, as observed in disorders associated with acute-phase reactions, is accompanied with concommitant rises in plasma factor VIII concentrations (Bloom 1979). Taken into account that the half life of factor VIII infused in animals is determined by the presence of endogenous vWF (Brinkhous et al. 1985), these observations clearly illustrate that vWF not only binds to factor VIII but also confers stability to factor VIII in vivo.