Disrupting the major contact interface limits human platelet–VWF interactions. (A) Ribbon representation of the human GPIbα–VWF-A1–OS1 ternary complex (left). The change in R-loop conformation imposed upon OS1 cyclic peptide (purple) binding to GPIbα (right). (B) Ristocetin-induced aggregation of human platelets in plasma VWF^HA1 in the presence and absence of OS1. (C) Accumulation of human platelets on surface-immobilized plasma VWF^HA1 (WSR of 1,600 s⁻¹) in the absence or presence of OS1 (n = 3). Images were obtained using a CCD camera and analyzed using Image-Pro Plus. (D) Human platelet-mediated thrombus formation in laser injured arterioles of VWF^HA1 mice who received an infusion of OS1 peptide or the human GPIbα function blocking antibody, mAb 6D1 (n = 7 mice per treatment condition; 1 arteriole per mouse). Fluorescent images were obtained using a ×20 water-immersion objective, a Yokogawa CSU-22 spinning disk confocal scanner, and a 488 nm laser line. The extent of thrombus formation was assessed for 2 minutes postinjury and its area determined by off-line analysis (Image IQ and Image-Pro Plus). Data are the mean ± SD. **P < .0001. ns, not significant (P > .05).