Introduction
Von Willebrand disease (vWD) is a common inherited bleeding disorder that is notable
for a high degree of variability in clinical presentation and the considerable heterogeneity
of its molecular basis. Confusion about the genetic origin of this disorder has existed
since its original description by Eric von Willebrand in 1926.1 Dr. von Willebrand coined the term “pseudohemophilia” to describe the disease in
the original pedigree. Though it resembled the bleeding diathesis of hemophilia, von
Willebrand also noted findings suggesting an abnormality in platelet function. The
severity of bleeding in this family varied widely from mild bleeding to severe hemorrhage,
the latter resulting in the death of the proband at the time of her fourth menstrual
period.
Von Willebrand incorrectly characterized the inheritance pattern in the original Åland
Island pedigree as X-linked dominant, because of the apparent greater frequency of
the disease in female patients. Now, it is recognized that the greater frequency was
largely by chance and due to increased penetrance related to the hemostatic stresses
of menstruation and pregnancy. Nonetheless, von Willebrand clearly distinguished the
inheritance pattern of vWD from that of classic hemophilia. It is now known that vWD
is due to either quantitative or qualitative defects in von Willebrand factor (vWF),
encoded by a gene on chromosome 12, whereas hemophilia is due to mutations in the
factor VIII gene on the X chromosome.2
