Unfolded VWF reduces PS plasma anticoagulant activity. Plasma thrombin generation was measured in pooled healthy normal plasma (HNP), single donor plasma, PS-DP, plasma from a patient with VWD3, or VWF-DP in the presence or absence of exogenous APC (5 nM; A) or thrombomodulin (20 nM; B-C) and the presence or absence of short-term shear (1 minute; A-B) or long-term shear (1 hour; C). Paired t tests were performed with each individual data set, comparing plasma with or without shearing; ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .001. PS-DP, PS-depleted plasma, VWD3, type 3 von Willebrand disease, VWF-DP, VWF-depleted plasma.