Sources familiar with the situation told Flanagan after the game that the Rams fear Amendola, who was seen with his right arm in a sling, broke his collarbone. Amendola will have a CT scan on Friday morning.
"Ya, it's big, I'm not gonna lie," Rams quarterback Sam Bradford told Flanagan after the game. "Obviously, he's a big part of the offense. A lot of what we do runs through him. He went down last year, and it really hurt us. I feel confident about our guys we got this year, and I think it just opens up a spot for someone to step up and make some plays."
Amendola, who's coming off a major elbow injury that cost him nearly all of the 2011 season, was shown by NFL Network cameras in the bowels of the Edward Jones Dome letting out a loud yell before firing his helmet against the wall.
Amendola was second in the NFL in receptions entering Week 5. The Rams will ask Brandon Gibson, Austin Pettis and rookies Chris Givens and Brian Quick to step up with Amendola out of the mix. Givens caught a long score Thursday night, but this is an untested group to put it nicely.
Rams safety Quintin Mikell also left in the second quarter with a head injury and missed the rest of the game. He originally was listed as questionable to return.
Follow Gregg Rosenthal on Twitter @greggrosenthal.