Dean hadn't said anything at first. He just listened, wondering what might Fred might have meant. Or more, wondering why he knew exactly what she meant but was doing his damnedest to pretend he didn't. He didn't want to know that whatever had happened had been Sam's fault. That Sam had decided to take a path that simply wasn't the Winchester way, not unless they could help it. They could have found a better way, a safer way, something that kept everyone alive, but Sam had gone for the darker more efficient way.
"Does he know you remember?" Dean stopped thinking about what had happened. It was just that quick. "Do you think he knows?" They had to protect her; he didn't know how hard Sam had tried to avoid his soul, but shooting someone like Fred wasn't exactly a sign of being willing to turn to the light side again. Plus, they didn't know if Sam was Sam. Whatever Sam was...had to be stopped.