ON THE ROLE OF VON-WILLEBRAND-FACTOR IN PROMOTING PLATELET-ADHESION TO FIBRIN IN FLOWING BLOOD

Platelet adhesion to fibrin at high shear rates depends on both the gl ycoprotein (GP) IIb:IIIa complex and a secondary interaction between G PIb and von Willebrand factor (VWF). This alternative link between pla telets and vWF in promoting platelet adhesion to fibrin has been exami ned in flowing whole blood with a rectangular perfusion chamber. Optim al adhesion required both platelets and vWF, as shown by the following observations. No binding of vWF could be detected when plasma was per fused over a fibrin surface or when coated fibrinogen was incubated wi th control plasma in an enzyme-linked immunosorbent assay. However, wh en platelets were present during perfusion, interactions between VWF a nd fibrin could be visualized with immunoelectron microscopy. Exposure of fibrin surfaces to normal plasma before perfusion with severe von Willebrand's disease blood did not compensate for the presence of plas ma VWF necessary for adhesion. vWF mutants in which the GPIIb:IIIa bin ding site was mutated or the GPIb binding site was deleted showed that VWF only interacts with GPIb on platelets in supporting adhesion to f ibrin and not with GPIIb:IIIa. Complementary results were obtained wit h specific monoclonal antibodies against vWF. Thus, vWF must first bin d to platelets before it can interact with fibrin and promote platelet adhesion. Furthermore, only GPIb, but not GPIIb:IIIa, is directly inv olved in this interaction of VWF with platelets. (C) 1995 by The Ameri can Society of Hematology.