The Brazil midfielder was substituted before half-time after a collision with goalkeeper Matej Kovar, immediately signalling to the bench that he could not continue. Newcastle still ran out comfortable winners, but the injury to their skipper slightly dulled an impressive European night.
Speaking after the match, Howe said: "He's a little bit sore and there's a bit of swelling around his ankle. We hope it's not serious, but it's difficult to know at this stage. It's always a worry when a player has to come off like that."
On the pitch, Newcastle were in control from early on. Yoane Wissa opened the scoring inside the first ten minutes with his first Champions League goal, before turning provider to set up Anthony Gordon for a simple finish midway through the first half. Harvey Barnes sealed the result in the second half to complete a dominant display.
Howe was delighted with his side's overall approach. "It was a really good performance from us," he said. "PSV are a difficult opponent, tactically they are tough to play against. I thought we were rewarded with some really good goals."
He singled out Wissa for special praise, adding: "It was a really good night for Yoane. In part he came to this club for nights like today. I thought a lot of players gave their best individual performances for a while, and Anthony Gordon is one who has really excelled in this competition."
There was also a memorable moment late on when teenager Lewis Miley briefly wore the captain's armband after Kieran Trippier replaced Guimaraes as skipper. "It was unscripted and unplanned," Howe said. "Typical Kieran, thinking of other people. It was a great moment for Lewis."
The win lifted Newcastle into seventh place in the league phase and guaranteed at least a play-off spot. They are now well placed to push for automatic qualification, with a key away match against Paris Saint-Germain to come next week.
However, Howe was keen to keep the focus on domestic matters first. "It's one step at a time," he said. "Aston Villa comes first. The Premier League is so important and that will be a really tough game."
For now, Newcastle can reflect on a commanding European performance, and wait anxiously for news on their captain's ankle.
Tottenham had enjoyed a positive night on the pitch against Borussia Dortmund, but Thomas Frank admitted the victory came at a heavy cost after Lucas Bergvall was ruled out for up to three months with an ankle injury.
Hansi Flick has praised Barcelona's resilience after a demanding 4-2 Champions League win away to Slavia Praha on Wednesday, but admitted his satisfaction was tempered by concern over Pedri's injury.
Kim Min-Jae was sent off, but Vincent Kompany was quick to defend his defender after Bayern Munich secured a 2-0 win over Union Saint-Gilloise despite playing more than 25 minutes with ten men.
Luciano Spalletti has praised Juventus for stepping up in a crucial 2-0 Champions League win over Benfica, but the Juve coach made it clear that higher standards were still required as the pressure builds in Europe.
