Activation-independent platelet aggregation mediated by multimeric VWF or isolated VWF A1 domain. Perfusion over immobilized VWF of washed blood cells suspended in Hepes/Tyrode buffer, pH 7.4 (see legend to Figure 2B). In the presence of soluble multimeric VWF (+VWF; 20 μg/mL), single platelets adhere when the shear rate is 2500 s^–1, and elongated, firmly adherent activation-independent aggregates form at 23 000 s^–1. In contrast, in the presence of soluble dimeric VWF A1 domain (+dA1; 5 μg/mL), large rolling aggregates form on the surface when the shear rate is 2500 s^–1, but only single platelets adhere when the shear rate is 23 000 s^–1. Bar graph: Quantitative evaluation of the number of activation-independent aggregates with cross-sectional area more than 100 μM² present at positions exposed to the indicated wall shear rates in the presence of soluble VWF (VWF multimers) or isolated dimeric A1 domain (dVWFA1). Measurements performed in a field of view = 120 000 μM². Images from Video S10.