Pardew insisted every precaution had been taken before Santon signed - including thorough investigation of his medical history.
Santon first damaged his right knee in April 2009 on international duty and underwent an operation in 2010 to correct the problem. But it looks like keyhole surgery will be required.
"David has had a few injuries in the last couple of years and that is not ideal especially as he has been through a really thorough medical," he said. "He is a little bit unlucky if I am honest as we are only a week or so down from the medical.
"At Premier League level, with most clubs the medicals are very thorough irrespective of a player's past history. He has had MRIs and his medical would have been no different from anyone else's just as it was the same for Demba Ba, who has a history of knee problems.
"We did not have any plans to go beyond that for Santon because it did not flag up. We did not try to protect him in the medical. I just think he has been unlucky because there were no problems after reserve game."