Hermann Hreidarsson and Danny Webber were stretchered off, while David James limped away with a calf injury.
Sheffield United Danny Webber hit a post and Wigan had Lee McCulloch sent off in a frantic second period.
The Blades had a late chance to equalise against 10-man Wigan but Danny Webber hit the post when one-on-one with keeper Mike Pollitt.
Only a linesman's flag denied the visitors the opener, Danny Webber flicking Nadir Belhadj's cross in at the near post from an offside position.
The on-loan Lyon striker then turned provider for Danny Webber to cut in and drive home, before stabbing in his side's third after a Simonsen mistake.
In another warning for North End, Danny Webber - on loan from Manchester United - made space for himself inside the area and drove narrowly over the crossbar.
Stoke were thumped by Portsmouth to go out of the Carling Cup with two goals from Frederic Piquionne, and one each from Danny Webber and Kanu earning Pompey victory.
The game was being played in a frantic atmosphere, on and off the pitch, and Danny Webber - a half-time substitute for Christian Nade - was agonisingly close to an equaliser for Sheffield United.
But their day - and arguably season - was summed up by the sight of Danny Webber and David James having to go off injured in the closing minutes, leaving Portsmouth to finish the match with 10 men.
The full-back latched on to John Utaka's intelligent back heel inside the box and rifled his shot into Kompany as the ball looped over Given and on to the crossbar, with Ireland clearing the danger with Danny Webber poised to pounce.
West Ham took the lead when Younes Kaboul's headed clearance looped in off the chest of Matthew Upson in the 52nd minute before Danny Webber rescued a point for Pompey in the 76th minute when he slotted the ball through the legs of Hammers goalkeeper Robert Green.
But the president, his counsel, the lawyer for Trooper Danny Ferguson and Federal Judge Webber Wright had no idea what they and Linda Tripp were planning.
Portsmouth were only inches away from a second before half-time, too, but O'Hara's fine curling effort crashed off the bar and Danny Fox then bravely denied Webber's follow-up shot.
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