Wales full-back Morgan Stoddart's hopes of going to the World Cup are over after he broke his left leg in their 23-19 defeat by England.
"It looks like a bad break," said coach Warren Gatland. "It's a shame for him."
Stoddart suffered the injury in the 48th minute at Twickenham, having gone from bench to starting line-up in a late pre-match reshuffle.
That was prompted by Stephen Jones' withdrawal shortly before kick-off with a suspected calf strain.
Rhys Priestland went to 10 and Stoddart took the number 15 jersey.
Stoddart's injury happened when he was tackled by Delon Armitage, having intercepted a pass from the England player.
"You have got to feel for him [Stoddart]" said Gatland.
"We have been joking in the past, calling him 'Glass' and 'Crystal' because he does pick up a few injuries, but to get an injury like that...you hope he recovers as quickly as possible.
"He did look dangerous with the ball in hand, he looked threatening. It was a shame he picked up that injury."
England scrum-half Danny Care stopped play when he realised the extent of the Scarlet's injury.
"Jamie Roberts was on the floor saying he was in trouble. Dylan (Hartley) said the same.
"I think he was screaming, he was definitely in pain so there it was safety first, stop play and get him off the pitch.
"If someone is injured you want to stay away from him, you don't want to fall on him or anything. Anyone would have stopped the play.
"It is such a sad way to get injured. That is the sport we are in. It is a tough, physical sport, injuries are going to happen. You have to be lucky over the next few games."
Gatland says Jones was withdrawn as a precaution, adding: "Stephen had a tight calf before the game and we didn't want to take any chances.
"If he had torn the calf, that is six weeks out."
Jones, 33, was due to make a record 101st Wales appearance, but watched from the sidelines as fellow Scarlet Stoddart suffered the injury.
Travelling reserve Lloyd Williams - the Cardiff Blues scrum-half - went on to the bench, leaving Wales without specialist pivot cover.
Wales captain Sam Warburton said: "It is gutting for Morgan. He had a real good shout of making the World Cup squad."