The 26-year-old, who has enjoyed a period of good form in recent weeks while deputising for the injured Ben White, crashed into Tottenham Hotspur forward Heung-min Son in the 33rd minute and was shown a second yellow card by referee Paul Tierney.
Holding had picked up his first booking seven minutes earlier, bringing down Son again shortly after Harry Kane gave Spurs the lead from the penalty spot. It didn't take long for Spurs to capitalise on boasting the extra man in the crucial top-four clash, as Kane headed home his second goal of the game from a flicked-on corner.
In commentary, former England defender Gary Neville said: "What is he doing? What is he doing? Oh my goodness. I am watching the run and he has a jab with the elbow. He has been erratic for the first part of this game, he has been rash, he has been unsteady and he has to go."
Jamie Redknapp also said: "He had two incidents before he'd even been booked.
"We spoke before the game about derby matches, a match of this magnitude, you need cool heads, don't do anything silly. The second one with Son is silly, he is doing judo moves on the football pitch. Then he gets caught again, and then it becomes an accumulation and then it becomes a booking.
"Once you get booked, he has to be so careful because he does not want to get too tight to Son because he can run in behind you. You already have a major problem with him, he is too quick, too strong, and certainly do not get too tight to him, like this for his second yellow. That even could be straight red card because he puts his elbow up, it is a really poor decision from Rob Holding."
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