Blood, Vol. 93 No. 1 (January 1), 1999:
pp. 193-197
von Willebrand Factor Elevates Plasma Factor VIII Without
Induction of Factor VIII Messenger RNA in the Liver
Randal J. Kaufman,
Andrew J. Dorner, and
David N. Fass
From the Howard Hughes Medical Institute and the Department of
Biological Chemistry, University of Michigan, Ann Arbor, MI; the
Genetics Institute Inc, Andover, MA; and the Mayo Medical School,
Rochester, MN.
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.
