Wales number eight Taulupe Faletau has undergone surgery to his broken right arm that rules him out of the remainder of the Guinness Six Nations.
It had been hoped Faletau would return for the final two rounds against Scotland and Ireland but Warren Gatland must complete the tournament without the powerful Bath star.
The fracture to his arm was incurred against Wasps in January when he was making his comeback from a similar injury to his forearm sustained in October.
"We're gutted for Taulupe but this is the best course of action for him moving forwards as a player," Bath director of rugby Todd Blackadder said.
"We will know more in terms of time frames following the surgery but we're looking forward to welcoming him back into the squad."
Offsetting Faletau's absence is the news that Leigh Halfpenny is available to line-up against England after being given the all-clear from concussion.
Halfpenny took a blow to the head against Australia on November 10 and has not played since but he could return for the Scarlets this weekend in time to prove he is ready for the title collision in Cardiff.
"To do full contact he has got to be symptom free and Leigh has been symptom free," Scarlets coach Wayne Pivac said.
"He trained with us last Thursday and Friday, and yesterday (Monday) he did everything – full contact and full tackling.
"We had a mini-game scenario, what we call level three, which is a game scenario so there is no hiding places.
"He was taking high balls, getting clattered. He did everything he needed to do.
"He goes back to Wales available, we feed back information, medical team to medical team, and I have passed a little note on to Warren. Warren will make a call on what he does from there."
British and Irish Lions wing Shane Williams, who played alongside Halfpenny during an 87-cap Wales career that ended in 2011, believes he would be an ideal selection at full-back against England.
Halfpenny is outstanding at patrolling the backfield, while also operating as a pinpoint goalkicker, traits that could counteract the laser-guided kicking game Eddie Jones' men have used to dominate Ireland and France in their opening two wins so far.
"When it comes to positioning and not letting the ball hit the pitch, Leigh is probably the best in the world," said Williams, who is taking part in the Exchange Everest Rugby Challenge on behalf of Wooden Spoon.
"It wouldn't surprise me at all if he slots straight back in at 15 because he's a good enough player to do that.
"If Leigh is involved, England are going to know that he is one of these guys that reads the game very well.
"And we also need those three points when they are on offer. England have been one of the best disciplined teams in the tournament so those three points are not going to come easy."
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