Genetics of classic von Willebrand's disease. II. Optimal assignment of the
heterozygous genotype (diagnosis) by discriminant analysis
CH Miller, JB Graham, LR Goldin and RC Elston
In classic von Willebrand's disease (vWd), assignment of the heterozygous
genotype for genetic studies and diagnosis for clinical purposes (which are
not exactly the same) are formidable problems. We have pointed out in the
first report in this series that almost 50% of the members of two large
kindred who transmitted this disease, and were therefore heterozygous, were
scored as normal by the usual tests of hemostasis. This report describes
how this large proportion can be significantly reduced by application of
discriminant analysis. Using linear discriminants in three
variables--coagulation factor VIII (VIII:C), factor-VII-related antigen
(VIIIR:Ag), and the ristocetin cofactor related to factor VIII
(VIIIR:WF)--we were able to classify as heterozygous more than 80% of the
transmitters in the two large kindred. It was of particular interest that
the four parents of two related vWd homozygotes could be scored as
heterozygous by discriminant analysis even though all their laboratory
tests were within the normal ranges.
Volume 54,
Issue 1,
pp. 137-145,
07/01/1979
Copyright © 1979 by The American Society of Hematology
