Haematologica Reports 2005; 1(issue 6): 9-14[prev][index][next]
The biology of von Willebrand factor and factor
viii-regulated release
S.L. Haberichter, Q. Shi, R.R. Montgomery
Blood Research Institute of BloodCenter of Wisconsin and Department
of Pediatrics of Medical College of Wisconsin Milwaukee, Wisconsin,
USA
The clinical association of factor VIII (FVIII) deficiency with
both hemophilia A and von Willebrand disease (VWF) has been
recognized for more than 50 years.1-3 However, the
mechanism by which regulated secretion of both proteins occurs,
remains controversial.1 Since FVIII is deficient in both
hemophilia A and severe von Willebrand disease (VWD), it was not
surprising to find that the reason for this observation was that
VWF (VWF) served as a carrier protein for FVIII.1 In the absence of
VWF, the unbound FVIII is rapidly proteolyzed — a process
that reduces its plasma half life from 12 hours to one to two
hours. Since patients with severe VWD still had a residual level of
FVIII between 3 and 8 IU/dL in the absence of detectable VWF,
infusion of VWF resulted in a delayed rise in plasma of FVIII over
the subsequent 12 to 24 hours, this was assumed initially to be
stimulation of FVIII synthesis, although today, it is recognized
that FVIII synthesis is probably progressing normally and it is
only in the presence of transfused VWF that the FVIII survival can
now normalize and give the clinical picture of the delayed rise in
FVIII. The purpose of this review is to establish the basis for how
a regulated storage pool, of both VWF and FVIII, is established.
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