Enhanced thrombin generation with D519V/E665V results in increased platelet and fibrin response to vascular injury. Intravital microscopy of laser-injured vessels was performed in HemA mice and the kinetics of platelet accumulation (A) and fibrin deposition (B) in response to D519V/E665V (filled black histograms) and BDD-FVIII (hatched histograms). The quantitation of the maximum clot size based on platelet-associated (C) and fibrin-associated (D) fluorescence is also shown. Comparison of the median maximum fluorescence (horizontal bars) shows a statistically significant difference between clots formed by animals dosed with BDD-FVIII (open circles) and D519V/E665V (filled circles); P < .0001 and P < .008 for platelet and fibrin maximum fluorescence, respectively. The BDD-FVIII data were derived from analysis of 85 clots from 9 mice; the D519V/E665V data were derived from analyzing 40 clots from 4 mice.