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Glycoprotein Ib, von Willebrand factor, and glycoprotein IIb:IIIa are all
involved in platelet adhesion to fibrin in flowing whole blood
RR Hantgan, G Hindriks, RG Taylor, JJ Sixma and PG de Groot
Department of Biochemistry, Bowman Gray School of Medicine, Wake Forest
University, Winston-Salem, NC 27103.
We have investigated the molecular basis of thrombus formation by measuring
the extent of platelet deposition from flowing whole blood onto
fibrin-coated glass coverslips under well-defined shear conditions in a
rectangular perfusion chamber. Platelets readily and specifically adhered
to fibrin-coated coverslips in 5 minute perfusion experiments done at
either low (300 s-1) or high (1,300 s-1) wall shear rates. Scanning
electron microscopic examination of fibrin-coated coverslips after
perfusions showed surface coverage by a monolayer of adherent, partly
spread platelets. Platelet adhesion to fibrin was effectively inhibited by
a monoclonal antibody (MoAb) specific for glycoprotein (GP) IIb:IIIa. The
dose-response curve for inhibition of adhesion by anti-GPIIb:IIIa at both
shear rates paralleled that for inhibition of platelet aggregation.
Platelet aggregation and adhesion to fibrin were also blocked by low
concentrations of prostacyclin. In contrast, anti- GPIb reduced adhesion by
40% at 300 s-1 and by 70% at 1,300 s-1. A similar pattern of shear
rate-dependent, incomplete inhibition resulted with a MoAb specific for the
GPIb-recognition region of von Willebrand factor (vWF). Platelets from an
individual with severe von Willebrand's disease, whose plasma and platelets
contained essentially no vWF, exhibited defective adhesion to fibrin,
especially at the higher shear rate. Addition of purified vWF restored
adhesion to normal values. These results are consistent with a two-site
model for platelet adhesion to fibrin, in which the GPIIb:IIIa complex is
the primary receptor, with GPIb:vWF providing a secondary adhesion pathway
that is especially important at high wall shear rates.
Volume 76,
Issue 2,
pp. 345-353,
07/15/1990
Copyright © 1990 by The American Society of Hematology
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