Initiation of Platelet Adhesion by Arrest onto Fibrinogen or Translocation on von Willebrand Factor

Abstract

We have identified two distinct mechanisms initiating the adhesion of flowing platelets to thrombogenic surfaces. The intergrin alpha IIb beta 3 promotes immediate arrest onto fibrinogen but is fully efficient only at wall shear rates below 600-900 s-1, perhaps because of a relatively slow rate of bond formation or low resistance to tensile stress. In contrast, glycoprotein Ib alpha binding to immobilized von Willebrand factor (vWF) appears to have fast association and dissociation rates as well as high resistance to tensile stress, supporting slow movement of platelets in continuous contact with the surface even at shear rates in excess of 6000 s-1. This eventually allows activated alpha IIb beta 3 to arrest platelets onto vWF under conditions not permissive of direct binding to fibrinogen. The coupling of these different functions may be crucial for thrombogenesis.

Shear‐induced platelet aggregation increases in patients with proximal and severe coronary artery stenosis

“…The present study focused on platelet aggregation but did not investigate platelet adhesion, another important function of platelets. The vWF has also been reported to play a role in platelet adhesion under high shear stress, 34 emphasizing the need to study shear-induced platelet adhesion in ischemic heart disease.…”

Ets transcription factors bind and transactivate the core promoter of the von Willebrand factor gene

“…von Willebrand factor (vWF) is a large multimeric glycoprotein that mediates adhesion and aggregation of platelets to the exposed subendothelium at high shear rates (Sadler, 1991;Savage et al, 1996). vWF also serves as carrier protein for the coagulation factor VIII in plasma and stabilizes its activity (Ruggeri and Ware, 1993).…”

Thrombopoietin increases platelet adhesion under flow and decreases rolling

“…First, there is a rolling phase in which the platelets become transiently coupled to the surface via glycoprotein Ib binding to the A-1 domain in VWF. Second, there is persistent adhesion via integrin a IIb b 3 binding to the RGD site in the A-3 domain of VWF (Savage et al, 1996). To investigate the effect of TPO on rolling and adhesion, whole blood was perfused at a shear rate of 1000/s over a VWFcoated surface and the movement of platelets was detected by real-time registration.…”

“…In the chamber, a VWF-coated coverslip was placed and continuously monitored by a fluorescence microscope (Orthoplan Flu, Leica, Germany) equipped with a LI-lowlight-level CCD camera (Lambert Instruments, Leutingwolde, the Netherlands) and a Sony video recorder. Platelets were prelabelled in whole blood with 10 lmol/l mepacrine (10 min, 37°C), a concentration known not to interfere with platelet adhesion or other platelet functions (Savage et al, 1996). Perfusion time was 5 min at a shear rate of 1000/s.…”