Model of platelet aggregation at various shear rates. (A) Platelet aggregation at shear rates below approximately 1000 s⁻¹ is predominantly dependent on the activation of integrin α_IIbβ₃ receptors and the presence of its ligand fibrinogen. (B) At shear rates up to about 10 000 s⁻¹ platelet aggregation is a 2-stage process. Platelets are initially captured to a growing aggregate via the GPIb/V/IX and integrin α_IIbβ₃ receptors binding to VWF and fibrinogen present at the aggregate surface. The formation of membrane tethers gives a mechanical advantage to adhesive bonds by reducing the level of force exerted on them.^17,53  (C) At extreme shear rates well above 10 000 s⁻¹ the aggregation of platelets is no longer dependent on the function of integrin α_IIbβ₃ receptors and tether formation. Instead, immobilized VWF combined with soluble multimeric VWF is capable of initiating large unstable aggregates of nonactivated platelets.¹²