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Three weeks ago, critical care pulmonologist Hugh Cassiere encountered something he hadn't seen in 24 years of practicing medicine.

A 45-year-old man arrived at the hospital where Cassiere works, North Shore University Hospital on Long Island, New York, with fever and severe fatigue — well-known symptoms of the coronavirus — and went on to test positive for it.

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But then the man developed a complication not usually associated with respiratory viruses: a blood clot in his leg that was so dangerous that doctors were forced to remove the leg below his knee. The development was totally unexpected, Cassiere said.

"He had no history of peripheral vascular disease, nothing that would predict" this outcome, Cassiere told NBC News. "That's how severe this clotting can be."

Cassiere isn't the only doctor who has noticed unusual clotting in patients with COVID-19, the disease associated with the coronavirus.

"We're used to patients that are critically ill having a high frequency of blood clots," said Dr. Mark Crowther, chairman of the Department of Medicine at McMaster University in Hamilton, Ontario, who is a member of the American Society of Hematology. "But nowhere near the magnitude that we're seeing in COVID patients."

A study from the Netherlands published this month looked at data on 184 patients in intensive care with COVID-19. Nearly a third were found to have clots, which is "remarkably high" for ICU patients, the study authors wrote.

Blood clot complications

Blood clots form when certain blood components thicken into a jelly-like mass. They can be life-threatening if they move to parts of the body like the heart, the lungs or the brain.

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It's unknown whether the coronavirus itself causes blood clots or whether the body's massive inflammatory response to fight the virus is what damages blood vessels and blood cells.

Whatever the mechanism, it's wreaking havoc on the sickest COVID-19 patients and doctors' ability to treat them.

Some physicians are reporting increases of patients in their 30s and 40s with COVID-19-related strokes that result when clots block blood vessels leading to the brain.

And blood from COVID-19 patients with kidney injuries is clotting so much, doctors have found, that it's clogging the filters in dialysis machines.

In some cases, intensive care doctors are finding that large catheters called cannulas are becoming clogged almost immediately in patients who are put on ECMO, a process that replaces the function of the heart and lungs if they're too damaged to work on their on own.

"As soon as you put the cannulas in and you turn the machine on, there's clotting," Cassiere said. "That is very, very surprising."

To counteract the clotting, physicians give patients blood thinners, usually medications called anticoagulants that make it harder for clots to form.

It's not uncommon for intensive care patients to be put on such blood thinners, and physicians know to watch for excessive bleeding.

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But complicating matters further, the drugs don't appear to be working for COVID-19 patients, even if they're given higher-than-usual amounts.

"I'm thoroughly surprised that we're not seeing a lot of bleeding, which is a little scary," Cassiere said. "In the back of my mind, I'm thinking, maybe the usual anticoagulation isn't enough."

Another option is anti-platelet medication, such as aspirin, which works by preventing platelets in the blood from sticking together. Experts say it's too soon to recommend such drugs for COVID-19 patients.

"There's no good data on whether anti-platelet therapy for COVID-19 patients makes sense," Cassiere said.

Another clue that COVID-19 is causing chaos in the blood system comes from a study published in the journal Cell in March, which showed that the virus infiltrates the body by binding to a type of receptor on cells called ACE2.

ACE2 receptors are often found in endothelial cells, located in the lining of the heart and blood vessels. One of the main jobs of the cells is to help control blood clotting and platelets.

But until more is known about exactly how the virus affects those cells and platelets, doctors are left in search of answers.

"Nobody knows what the correct way of preventing this clotting is or if we can even prevent it," Crowther said. "There are many studies going on now looking at various strategies."

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