The Eagles' thrilling three-point win over Gold Coast on Saturday was soured by a high injury toll that extended beyond the broken hand of Elliot Yeo and broken finger of Sam Butler.
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Selwood was a late withdrawal on Friday afternoon with Sharrod Wellingham earning a reprieve after he was initially dropped.
But Simpson revealed that Selwood's injury was not just a training mishap and might put his season in jeopardy.
"Selwood is in a bit of trouble," Simpson said.
"I think his foot is worse than what we hoped it would be. He'll miss multiple weeks.
"It's ankle related. There's something there that he's been carrying and probably his brave attitude towards it has probably hurt it a little bit because he's been carrying it since round three."
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Simpson believes Selwood's form had been affected by is ankle issue.
"We've been managing it," Simpson said.
"He's been getting better. But at training it wasn't quite right so we explored it a little bit further. We'll find out more on Monday."
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Luke Shuey was also a late withdrawal pre-game after failing to come up from a rolled ankle at training on Thursday.
"We had to give him until today to get it right," Simpson said.
"He did a fitness test and I just didn't want to stick a needle in him for him to play.
"We're hoping he is going to be OK next week."
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Instead of one man's misfortune being another's opportunity it was a case of two men's misfortune being another concern for West Coast.
Butler was the late replacement for Shuey and started at the sub.
Elliot Yeo broke his hand in the second term but fought on for 40 minutes before eventually being subbed out. Butler entered the game and broke his finger immediately, missing most of the last quarter.
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Simpson said Yeo was courageous to try and continue but his hand may keep him out for a while.
"Really good effort from him," Simpson said.
"Really brave. He played for at least 40 minutes with a broken hand.
"It's probably going to be one to four (weeks)."
Simpson said rested ruckman Dean Cox will be available for next week's clash with St Kilda at Etihad Stadium.
