The Dutchman was forced off with a hip injury in United’s 2-0 win over QPR at the weekend.
United are assessing his fitness, but the prolific forward only has just over a week to recover in time for the home tie with Madrid, with the score at 1-1 after the first leg.
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The reputation of the Premier League means it is the most popular and one of the most watched leagues in the world.
Five English clubs will compete in the last sixteen of the Champions League for the first time ever as Liverpool, Manchester United, Manchester City, Chelsea and Tottenham face some difficult away matches.