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 no ncovalent protein complex. Circulating levels of factor VIII are coordinate ly regulated with circulating levels of vWF in which the ratio is maintaine d 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 incr ease 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 fivefo ld increase in circulating factor VIII activity. Liver biopsies were taken pre- and post-vWF infusion for isolation of total messenger RNA (mRNA). Fac tor VIII-specific mRNA was measured by an RNAse protection assay. The resul ts showed no difference in the liver-specific factor VIII mRNA on vWF infus ion. These results indicate that the secondary rise in factor VIII levels i n response to exogenous vWF infusion is not dependent on increased steady-s tate levels of factor VIII mRNA in the liver. (C) 1999 by The American Soci ety of Hematology.