The studies used appropriate 'negative' and 'positive' control groups. Studies included intrinsic markers [kininogen profiling, high molecular weight kininogen (HK) and low molecular weight kininogen (LK) cleavages, western blotting of HK and LK, and kallikrein-alpha2 macroglobulin; extrinsic markers [TF and factor V11a]; other activation and fibrinolytic markers [prothrombin F1.2, FPA, TAT, tPA, PAI-I, D-dimer and plasma alpha2 antiplasmin]; platelet- endothelial markers [evaluation of activation dependent epitopes]. Unequivocal demonstration of contact pathway activation during VOC provided a crucial link between VOC and its accompanying phenomenon including pain, and inflammation. Finally, the studies provided a unique perspective on the continuum of hemostatic changes that unfolded during the course of SCD, and those that developed as vascular insufficiencies supervened in the adult.