Shear-induced platelet aggregation is important in physiological hemostasis and in the pathogenesis of arterial
thrombosis. It requires extracellular Ca2+,
platelet membrane glycoproteins Ib/IX and IIb/IIIa,
von Willebrand factor (vWF), and
ADP. We studied the effects of
desmopressin (
DDAVP), which increases plasma vWF levels and shortens the bleeding time, and of
ticlopidine, which inhibits platelet responses to
ADP, on shear-induced platelet aggregation. Eleven healthy volunteers were given oral
ticlopidine (250 mg b.i.d.) for 7 days. The same subjects were infused intravenously with
DDAVP (0.3 micrograms/kg body wt) before the first and after the last doses of
ticlopidine. The degree of platelet aggregation induced by shear stress at 25, 50, 75, and 100 dyne/cm2 in a cone-and-plate viscometer, plasma vWF levels, and the bleeding time were measured before and after each
DDAVP infusion. Plasma vWF levels and the extent of shear-induced platelet aggregation increased after
DDAVP and were correlated.
Ticlopidine partially inhibited shear-induced platelet aggregation both before and after
DDAVP infusion. The bleeding time, prolonged by
ticlopidine, was shortened by
DDAVP. Potentiation by
DDAVP of shear-induced platelet aggregation may be one mechanism by which the
drug shortens the prolonged bleeding time. Since shear-induced platelet aggregation can cause thrombotic occlusions in stenotic arterial vessels, our findings may explain the therapeutic efficacy of
ticlopidine in arterial
thrombosis.