von Willebrand Factor Elevates Plasma Factor VIII Without Induction of Factor VIII Messenger RNA in the Liver

Factor VIII and von Willebrand factor (vWF) circulate in the plasma as a noncovalent protein complex. Circulating levels of factor VIII are coordinately regulated with circulating levels of vWF in which the ratio is maintained at 1 molecule of factor VIII for 50 to 100 vWF subunits. Infusion of vWF into vWF-deficient animal models and human patients yields a secondary increase in circulating levels of factor VIII. We have studied the mechanism of the secondary rise in factor VIII in a porcine model of vWF deficiency. On infusion of vWF into a vWF-deficient pig there was an approximately fivefold increase in circulating factor VIII activity. Liver biopsies were taken pre- and post-vWF infusion for isolation of total messenger RNA (mRNA). Factor VIII-specific mRNA was measured by an RNAse protection assay. The results showed no difference in the liver-specific factor VIII mRNA on vWF infusion. These results indicate that the secondary rise in factor VIII levels in response to exogenous vWF infusion is not dependent on increased steady-state levels of factor VIII mRNA in the liver.