Effect of aspirin on platelet-von Willebrand factor surface expression on
thrombin and ADP-stimulated platelets
RI Parker and HR Gralnick
Clinical Pathology Department, National Institutes of Health, Bethesda, MD
20892.
Platelets contain a pool of endogenous platelet-von Willebrand factor (vWF)
that becomes expressed on the platelet surface when platelets are
stimulated by a variety of agonists. Maximal platelet-vWF expression occurs
in concert with platelet alpha-granule secretion. Aspirin (ASA) is known to
impair platelet activation and alpha-granule secretion by irreversible
inhibition of platelet cyclo-oxygenase. We studied native and ASA-treated
platelets for their ability to mobilize and to express platelet-vWF in
response to adenosine diphosphate (ADP) or thrombin. We found that each
agonist was effective in promoting increased platelet- vWF surface
expression on native and ASA-treated platelets. ASA-treated platelets
responded identically to native platelets to low (0.01 U/mL) and high (1.0
U/mL) concentrations of thrombin, while the ADP-induced increase in
ASA-treated platelets was only 50% to 60% of that for control platelets.
Measurement of secreted platelet-vWF and beta- thromboglobulin indicated
that the increase seen with ADP was largely independent of alpha-granule
secretion. Using monoclonal antibodies (MoAbs) against the platelet
glycoproteins (GP) IIb/IIIa and Ib (MoAbs 10E5 and 6D1, respectively), we
demonstrated that the ADP-induced increase in platelet-vWF expression on
control platelets primarily involved the binding of secreted platelet-vWF
to the platelet GPIIb/IIIa. In contrast, the increase in platelet-vWF that
occurred following ADP stimulation of ASA-treated platelets was largely
insensitive to GPIIb/IIIa blockade. No effect of GPIb blockade in
platelet-vWf expression was noted for either control or ASA-treated
platelets. When platelet shape change was prevented by the addition of
cytochalasin D, ADP-induced platelet-vWf surface expression on ASA- treated
platelets was reduced by more than 80%. Our data indicate that platelets in
which the cyclooxygenase pathway is blocked by the action of aspirin can
increase surface expression of platelet-vWf as a consequence of platelet
shape change. We speculate that this process exposes platelet-vWf bound to
GPIIb/IIIa, or possibly GPIb, within the surface connected canalicular
system.
Volume 74,
Issue 6,
pp. 2016-2021,
11/01/1989
Copyright © 1989 by The American Society of Hematology
