Heterogeneous phenotypes of platelet and plasma von Willebrand factor in
obligatory heterozygotes for severe von Willebrand disease
PM Mannucci, A Lattuada, G Castaman, R Lombardi, ML Colibretti, N Ciavarella and F Rodeghiero
A Bianchi Bonomi Hemophilia and Thrombosis Center, University of Milan,
Italy.
To characterize the heterogeneity of severe (type III) von Willebrand
disease (vWD), plasma and platelet von Willebrand factor antigen (vWF:Ag)
and ristocetin cofactor activity (Ricof) were measured in 28 obligatory
heterozygotes (ie, parents or children of probands from 15 different
kindreds with severe vWD). On the average, heterozygotes had low levels of
vWF in both platelets and plasma. There was, however, considerable
heterogeneity, with four distinct patterns. Eleven heterozygotes had
concordant reduction of vWF:Ag and Ricof in both plasma and platelets; five
had low levels of vWF:Ag and Ricof in plasma contrasting with normal levels
in platelets; eight had a peculiar pattern, the reverse of the above (ie,
low levels in platelets and normal levels in plasma); and in one, both vWF
measurements were normal in plasma and platelets. These patterns were
genetically determined: they were consistent in four couples of
consanguineous heterozygotes and in two couples carrying the same gene
deletion. Only the remaining three heterozygotes had no clearly
identifiable pattern. Other findings of this study were that although most
of the heterozygotes had normal bleeding times, the 7 of 28 who had
prolonged bleeding times had concordantly low levels of vWF measurements in
both plasma and platelets. In conclusion, this large series of obligatory
heterozygotes provides evidence for phenotypic and genotypic heterogeneity
of severe vWD.
Volume 74,
Issue 7,
pp. 2433-2436,
11/15/1989
Copyright © 1989 by The American Society of Hematology
