Syk inhibition affects both thrombus initiation and thrombus stability in human blood. (A) Effect of PRT060318 on thrombus volume after perfusion of human blood over collagen. Each point represents the mean ± SEM of 7 individuals. (B) Continuous, real-time thrombosis profiles of 1 representative experiment in which anticoagulated human blood was perfused through collagen-coated capillaries in presence of PRT060318 (0.12-10μM). PRT060318 affects thrombus stability (< 1μM) and thrombus growth (> 3μM). (C) Mean thrombosis profiles of experiments performed with blood from 4 individuals showing dethrombotic activity of PRT060318. After 250 seconds, blood treated with either DMSO (vehicle control) or 5μM PRT060318 was immediately perfused over the preformed, untreated thrombi. (D) Representative 3-dimensional photomicrographs corresponding to panel C. The base of the thrombi remained unaffected by the treatment indicating destabilization of the platelet–platelet interactions.