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Aurin tricarboxylic acid: a novel inhibitor of the association of von
Willebrand factor and platelets
MD Phillips, JL Moake, L Nolasco and N Turner
Baylor College of Medicine, Methodist Hospital, Houston, TX 77030.
Shear stress activated platelets undergo aggregation in the presence of
large or unusually large von Willebrand factor (vWF) multimers without the
addition of ristocetin or any other exogenous chemical. This phenomenon may
be analogous to the platelet aggregation that leads to thrombosis in the
narrowed arteries and arterioles of patients with atherosclerosis or
vasospasm. A triphenyl-methyl compound, aurin tricarboxylic acid (ATA),
inhibits shear-induced, vWF-mediated platelet aggregation in platelet-rich
plasma (PRP) in concentrations above 200 mumol/L and in buffer suspensions
of washed platelets at a concentration of 0.1 mumol/L. In a
concentration-dependent manner, ATA also inhibits ristocetin-induced,
vWF-mediated platelet clumping in both fresh and formaldehyde-fixed
platelet suspensions. This inhibition can be overcome by increasing the
concentration of vWF, following the kinetics of first order competitive
inhibition. ATA prevents the attachment to platelets of the largest vWF
multimeric forms found in normal plasma and of the unusually large vWF
multimers derived from endothelial cells. The rate of aggregation and
degree of inhibition by ATA is not accounted for by the binding of
ristocetin or calcium. Arachidonic acid- and adenosine diphosphate
(ADP)-induced aggregation are not inhibited by ATA. Platelets incubated
with ATA can be easily separated from the compound. However, ATA binds to
large vWF multimeric forms and inhibits their ristocetin-induced
interaction with platelet glycoprotein Ib. Because ATA also inhibits
shear-induced, vWF-mediated platelet aggregation in vitro in the absence of
ristocetin, it may be a useful prototype compound to impede the development
of arterial thrombosis in vivo.
Volume 72,
Issue 6,
pp. 1898-1903,
12/01/1988
Copyright © 1988 by The American Society of Hematology
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