Tom Dumoulin's Maglia Rosa battle Over after Huge 60 kph Crash
Movistar's Giro d'Italia contender Richard Carapaz won stage four on Tuesday as a mass fall in the peloton seven kilometres from the finish cost 2017 champion Tom Dumoulin a devastating four minutes in the overall standings
Dumoulin came second at both the Giro d'Italia and the Tour de France in 2018, as well as winning the 2017 Giro and the 2017 world championships time-trial, making him a chief contender in all major tours and races.
"For sure, the overall ranking is over for me," said Dumoulin, who is now in 56th position 4min 30sec behind race leader Primoz Roglic of Slovenia.
The fall saw a small group of eleven riders get away from the peloton, including overall leader Roglic and two of his chief contenders to win the Giro, Britain's Simon Yates and Astana's Miguel Angel Lopez.
Ecuador's Carapaz made a long-range sprint for the line from more than 600 metres out with only Australia's Caleb Ewan and UAE's Diego Ulissi capable of challenging and ending second and third respectively.
Roglic, a former ski jumper, finished two seconds behind the trio, gaining 16 seconds on all his chief rivals for the 2019 title.
Dutchman Dumoulin freewheeled most of the way to the finishing post after his fall with blood streaming from a knee, with his chances of winning the title in tatters.
The 28-year-old was then whisked away to hospital for x-rays as he was unable to bend his knee.
"I was leading the peloton so I simply could not avoid it," continued Dumoulin.
"There is no fracture, which is good news, but my knee is very swollen."
"I was not able to develop power in the last few kilometres, so I don't know how I'll be tomorrow (Wednesday), for sure, the overall ranking is over for me."
Sunweb sports director Michiel Elijzen admitted Dumoulin's chances had been massively compromised.
"It looks like it's over for the GC," he said referring to the overall standings.
"It's hard. We came here to win the Giro but after four stages if you are four minutes off the leader..."
"We just have to wait and see if he can continue in the Giro," he said.
Tour of Spain winner Yates was also caught up in a second crash, on a roundabout with around six kilometres to go.
The 26-year-old remounted and chased hard, limiting the damage to just 16sec behind Roglic, who was the only rider to avoid the carnage.
"Everyone was fighting for position on a roundabout and a rider slid out in front of me," said Yates.
"I've hit my knee and hip, just on the left hand side, but I'm OK. We'll see how I pull up tomorrow, it's always worse in the morning, but the Giro is long."
Carapaz last year became the first Ecuadorian winner of a Giro stage, going on to take overall fourth place and just missing out on the best young rider's white jersey.
One year on, Carapaz has hit form at the right time despite losing more than a minute because of mechanical problems in Monday's stage.
"I lost time yesterday, so I wanted to make some up," said Carapaz, 26, who was born high in the Andes at 3,000 metres altitude.
"I was a little angry about it, but I didn't expect to win today. Our plan was just to protect Mikel Landa so as not to lose time, but the crash at the end changed everything."
"I was up against sprinters for the stage win so I had to anticipate their action. "
"I picked the perfect moment to attack, I knew if I went off with 600 metres to go I could hold on until the line."
Wednesday's fifth stage is a short 140km run from Frascati, just south of Rome, to Terracina where a 1.5km home straight should provide a perfect platform for a spectacular sprint finish.