The role of von Willebrand factor and fibrinogen in platelet aggregation under varying shear stress

Yasuo Ikeda, Makoto Handa, Koichi Kawano, Tetsuji Kamata, Mitsuru Murata, Yohko Araki, Hironobu Anbo, Yohko Kawai, Kiyoaki Watanabe, Ichiro Itagaki, Kiyotaka Sakai, Zaverio M. Ruggeri

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557 Citations (Scopus)


Exposure of platelets to shear stress leads to aggregation in the absence of exogenous agonists. We have now found that different adhesive proteins and platelet membrane glycoproteins are involved in aggregation depending on the shear stress conditions and the concentration of divalent cations in the medium. When blood is collected with trisodium citrate as anticoagulant, which causes a decrease in the levels of external ionized calcium ([Ca2+]0), platelet aggregation can be induced under low shear force (12 dyn/cm2) and is mediated by fibrinogen binding to the glycoprotein IIb-IIIa complex. Aggregates formed under these conditions are not stable, and when shear force is increased to 68 dyn/cm2, disaggregation results. By contrast, platelets from blood collected with hirudin as anticoagulant, wherein [Ca2+]0 is within normal plasma levels, do not undergo low shear-induced aggregation; however, after exposure to a shear force above 80 dyn/cm2, aggregation is observed but only when von Willebrand factor is present and can interact with both its platelet binding sites, glycoprotein Ib-IX and glycoprotein IIb-IIIa. Fibrinogen is not involved in high shear-induced aggregation which, in fact, occurs normally in patients with severe afibrinogenemia. Thus, von Wullebrand factor in the absence of exogenous agonists can mediate platelet aggregation in experimental conditions that may mimic the hemorheological situation of partially occluded arteries. This pathway of platelet aggregation involving only one adhesive ligand and two membrane adhesion receptors may play a relevant role in thrombogenesis.

Original languageEnglish
Pages (from-to)1234-1240
Number of pages7
JournalJournal of Clinical Investigation
Issue number4
Publication statusPublished - 1991 Apr


  • Cell adhesion
  • Thrombus formation
  • Vascular occlusion

ASJC Scopus subject areas

  • Medicine(all)


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