Leech antiplatelet
protein (LAPP) is a specific inhibitor of
collagen-induced human platelet aggregation and adhesion to
collagen under static conditions. Recombinant LAPP (rLAPP) and
L-366,763 (acetylated-Cys-Asn-Pro-Arg-Gly-Asp-Cys-NH2), a peptidyl
fibrinogen receptor antagonist, were evaluated in an anesthetized baboon
thrombosis model using a
collagen-coated graft segment of an arteriovenous shunt to elicit
thrombus formation. Animals were randomized to receive systemic
intravenous administration of rLAPP (100 micrograms.kg-1 x min-1; n = 5),
L-366,763 (8.5 micrograms.kg-1 x min-1; n = 3), or saline (n = 3). Despite complete and selective inhibition of
type I collagen-induced ex vivo aggregation of platelets, rLAPP had no significant effect on the rate or the extent of 111-In-labeled platelet deposition onto the
collagen graft and no effect on template bleeding time. In contrast,
L-366,763 completely prevented platelet deposition, maintained blood flow, and significantly prolonged bleeding time at the dosage that inhibited ex vivo aggregation in response to all agonists studied. In this study, the absence of an antithrombotic benefit of rLAPP contrasted sharply with the efficacy of the
fibrinogen receptor antagonist. These results demonstrate that specific inhibition of
collagen-mediated platelet aggregation alone is not sufficient to prevent platelet-dependent
thrombosis in this baboon model.