Further specificity characterization of von Willebrand factor inhibitors
developed in two patients with severe von Willebrand disease
MF Lopez-Fernandez, R Martin, C Lopez-Berges, F Ramos, N Bosch and J Batlle
Department of Hematology, Hospital Juan Canalejo, La Coruna, Spain.
Circulating inhibitors against von Willebrand factor (vWF) that show the
properties of heterologous IgG antibodies have been described in a few
patients with severe von Willebrand disease (vWD). The present study
provides further characterization of inhibitors from two patients with
severe vWD. Inhibitors in both, like polyclonal rabbit antibody, detected
all sizes of multimers and the complex structure of each multimer from
platelets and plasma of normal individuals as well as from plasma of
patients with IIA, IIB, and IIC vWD. Both inhibitors and the rabbit
antibody reacted mainly with the intact 225-Kd vWF subunit and the 189-H
and 140-Kd fragments in contrast to monoclonal antibodies specific for vWF
fragments that detected a higher relative proportion of 176-Kd fragment.
Furthermore, all these antibodies recognized fragment III, although one
inhibitor and rabbit polyclonal antibody reacted poorly and the other
inhibitor did not react at all with reduced fragment II of vWF digested
with Staphylococcus aureus V-8 protease. These data suggest that although
human inhibitors from severe vWD patients may behave, to some extent, as
polyclonal heterologous antibodies against native vWF, the former show
striking differences in their target specificity as well as a much broader
specificity than that described for human factor VIII inhibitors.
Volume 72,
Issue 1,
pp. 116-120,
07/01/1988
Copyright © 1988 by The American Society of Hematology
