Distinct mechanisms initiating platelet aggregation at various shear rates. (A) Platelet aggregation at shear rates < 1000 s−1 is predominantly mediated by the interaction of fibrinogen with integrin αIIbβ3. Under these conditions, stable aggregation typically occurs between shape-changed platelets. (B) At shear rates between 1000 and 10 000 s−1, a distinct 2-stage aggregation process can be identified. The initial formation of aggregates occurs between discoid platelets, is mediated by membrane tethers, and is dependent on the adhesive function of both GPIb and integrin αIIbβ3. Conversion of reversible aggregates to stable aggregates is associated with platelet shape change and is dependent on the generation of soluble agonists, particularly ADP. (C) At shear rates > 10 000 s−1, platelet aggregation can be initiated independent of integrin αIIbβ3 or platelet activation and is exclusively mediated by the VWF-GPIb interaction. Although the initial aggregates form between discoid platelets, at such high shears, the platelets adopt a smooth spherical morphology and roll (translocate in a rotational manner) across the VWF surface (unpublished observations, Erik Westein and Shaun P. Jackson). (Figure was adapted with permission from Maxwell et al.59 )
