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A new von Willebrand variant (type I, New York): increased ristocetin-
induced platelet aggregation and plasma von Willebrand factor containing
the full range of multimers
HJ Weiss and II Sussman
We report three members of a family who had reduced levels of plasma von
Willebrand factor (vWF) and increased ristocetin-induced platelet
aggregation (RIPA) (aggregation of platelet-rich plasma with ristocetin at
a concentration of 0.45 mg/mL), as previously reported in type IIB and
pseudo-von Willebrand's disease (vWD). However, in contrast to the latter
two disorders in which the larger vWF multimers are absent in plasma, the
entire range of vWF multimers was observed in the patients' plasma after
sodium dodecyl sulfate-agarose gel electrophoresis, and all vWF multimers
(including the largest) were present in the same proportion as in normal
plasma and type I vWD. Thus, despite increased RIPA, the levels and
multimeric pattern of vWF in this family's plasma were indistinguishable
from those in type I vWD in which RIPA is usually decreased. Addition of
ristocetin to the patients' platelet- rich plasma resulted in the removal
of vWF (and, more selectively, of the large multimers) at lower
concentrations of ristocetin than normal, as in type IIB and pseudo-vWD.
The defect in the patients was localized to their vWF, which had an
enhanced capacity for aggregating washed normal platelets in the presence
of low concentrations of ristocetin and for aggregating pseudo-vWD
platelets (in the absence of ristocetin). Both glycoproteins (GP) Ib and
IIb-IIIa were involved in the enhanced aggregation response. RIPA (at low
ristocetin concentrations) in the patients' platelet-rich plasma was
abolished by a monoclonal antibody (AP1) to GPIb and was markedly reduced
by monoclonal antibodies (10E5 and LJP9) that block adenosine diphosphate
and thrombin-induced binding of vWF and fibrinogen to GPIIb-IIIa but was
unaffected by an antibody (LJP5) that only blocks vWF binding. Partial
inhibition of the initial aggregation slope (and complete inhibition of
second phase aggregation) was achieved with creatine phosphate/creatine
phosphokinase. EDTA blocked second-phase aggregation but was without effect
on the initial slope. The findings in this family combine some features of
both type I vWD (normal pattern of vWF multimers in plasma) and type IIB
vWD (increased RIPA) and further demonstrate the increasing complexity of
the structure-function relationships in vWD.
Volume 68,
Issue 1,
pp. 149-156,
07/01/1986
Copyright © 1986 by The American Society of Hematology
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