As more people around the world are infected with Covid-19, were learning that the novel coronavirus can not only cause severe respiratory illness, but also can attack just about every major organ system in the body. And lately doctors have been sounding the alarm about a disturbing new outcome: blood clots and strokes, which are striking even healthy young people with no known risk factors and sometimes no other symptom of the virus.

An April 28 report in the New England Journal of Medicine details the cases of five people, ages 33 to 49, in New York City who had strokes and subsequently tested positive for Covid-19. All of them had large-vessel strokes outside of the hospital before experiencing other severe symptoms of the virus; one of them has since died.

It was very surprising to see the increase in this large-vessel stroke in young people, Thomas Oxley, a neurosurgeon at Mount Sinai in New York and a coauthor of the new report, tells Vox. As he explains, The bigger the vessel, the bigger the stroke.

Its the biggest story emerging about Covid-19, he adds. The rate of large-vessel stroke victims under 50 they saw was seven times higher than before the pandemic.

Blood clots are also causing other unexpected problems for Covid-19 patients. For example, Broadway actor Nick Cordero, who has been hospitalized since March with severe Covid-19, had his right leg amputated earlier this month after doctors were unable to control clotting there.

And many patients are developing small clots in their lungs, reducing the amount of oxygen they can move into their bodies. For others, their blood is clogging dialysis machines (which has been a problem due to the amount of kidney failure this illness is also causing).

Im a hematologist, and this is unprecedented, says Jeffrey Laurence of Weill Cornell Medical College, who has been in the field for three decades. This is not like a disease weve seen before.

Nearly every patient he has seen for blood disorders in the past month and a half has had Covid-19. Ive never had so many consults in my life. These people are clotting, and we cant shut it off.

Doctors and researchers are racing to figure out why this is happening, and how they might be able to best use existing therapies, such as blood thinners, to mitigate it in patients. The clots and strokes also add to the list of potential symptoms some people with Covid-19 might experience early on and gives another possible reason that the number of coronavirus-related deaths around the country is looking far larger than those officially being counted in hospitals.

When we get injured, we depend on our bloods ability to clot to stop the flow of blood. Clotting is a complex process that involves small cell fragments called platelets congregating and changing shape, proteins that help even more cells bind together, and the secretion of substances called blood clotting factors. If any of these processes go off course, people can experience excessive bleeding, which can be life-threatening.

On the other end of the spectrum, sometimes clots form inside blood vessels (more rarely, in arteries) without an injury. These can cause serious harm and sometimes death. There are many risk factors for developing internal blood clots, including smoking, obesity, heart disease, and others. And, now, it looks like Covid-19 is a risk factor as well.

Some clots remain in the place where they form and are known as thrombosis. This can cause severe pain and swelling. These clots can also travel to or form in a major organ, where they can do even more serious damage.

For example, a clot in the leg can travel up to the lungs, cutting off blood flow and causing a pulmonary embolism (which can lead to death or permanent lung damage). A clot can also flow to the heart, triggering a heart attack. And one in or near the head can block blood flow in part of the brain, bringing on a stroke.

Small early studies and case reports about the link between the novel coronavirus and blood clots are now pouring in. For example, one team in the Netherlands followed 184 severe Covid-19 patients who were receiving treatment in three different intensive care units. They found that 31 percent of these people had some sort of blood clotting issue, a percentage they call remarkably high.

Other data is emerging with similar implications. In patients with severe disease, various forms of blood clots are estimated to occur in 15-35 percent of patients, Behnood Bikdeli, a cardiology fellow at Columbia University Medical Center, tells Vox. And these clots, especially the small ones, could impact the illness severity and involvement of many of the organs, he says. (He and an international team of dozens of researchers published an April review of clotting issues in the Journal of the American College of Cardiology.)

Laurence has been studying small blood clots in HIV/AIDS patients for decades. In March, a dermatologist sent him a photo of surprising skin lesions on a young man who was severely ill with Covid-19. Laurence was stunned. Its a picture of microvascular clotting, where you can see exactly where the vessels have clotted, he says. He started wondering if something similar might be happening in the lungs.

Just hours later, another doctor called, giving him access to an autopsy of a different Covid-19 patient. Not only did this individual have small clots in the skin but also in his lungs. (Laurence and his colleagues published descriptions of these and three other cases of severe clotting in an April Translational Research paper.)

The presence of small clots in the lungs is disturbing, but it also might help to explain a puzzling trend medical staff have noticed in some Covid-19 patients. When people develop more advanced illness, their lungs can become stiff, making breathing on their own very difficult. This leads to a drop in blood oxygen if they are not on mechanical ventilation.

But health care workers have seen many patients with low oxygen levels but who still have fairly flexible lungs, Laurence explains. This points to the presence of microvessel clots [in the lungs] shutting off the ability of people to bring oxygen into their blood, he says. (He also noted that sustained time on a ventilator can, itself, increase lung stiffness, which could have been throwing off clinicians who were seeing that as an outcome of the illness, and perhaps along the way missing signs that something else was going on.)

Laurence also describes the multitude of people sick with Covid-19 whose blood clots are plugging up the dialysis machines in their wards. Beyond that, he says, even as the nurses are drawing their blood, its clotting in the tubes, and theyre on full doses of Heparin and other blood-thinning medications. Everyone is seeing a similar kind of thing, he says.

These observations also bear out in autopsies.

A team of Chinese researchers that looked at 183 people hospitalized with Covid-19 pneumonia in Wuhan, China, found evidence of clotting in 71 percent of those who died but less than 1 percent of those who didnt. (Notably, this paper was published early in the pandemic, in February.)

The prevalence of blood clots also raises the question of whether some stroke or heart attack home deaths in recent months were actually linked to Covid-19. Its yet another possible way Covid-19 fatalities might be being undercounted. Many people who have already died are not currently tested for Covid-19 (often in the interest of preserving tests for those who are still alive). But more widespread posthumous testing could help clarify the full impact of this disease.

Scientists still dont understand exactly what is triggering this excessive blood clotting. (Some viruses, such as the Ebola virus, cause extreme bleeding, but others, such as HIV, can trigger small clots.) And its not yet clear if these changes in the blood are from the virus itself or the bodys immune response to the infection.

One of the hypotheses has to do with how the virus gains entry to our cells. Researchers have found that this coronavirus manages to sneak into our cells via a specific type of receptor known as ACE2. These are prominently found in the lungs, which might explain why so much of the viruss damage has been centered there. But ACE2 receptors are also very common along the walls of blood vessels throughout the body, Oxley explains. So its possible that its presence there is spurring additional inflammation of the vessels, prompting the formation of blood clots.

Laurence also points to this inflammatory problem. It is this insidious feedback loop of inflammation, he says. And once its going, he says, you cant intervene in that system effectively.

To be sure, sustained immobility, such as in a hospital bed, can increase the risk for blood clots, but the rates currently being reported in Covid-19 patients is way above what would normally be expected, Laurence notes.

With the new evidence about this viruss potential effect on the blood, doctors at many major medical facilities have begun administering low doses of preventative blood thinners to Covid-19 patients.

Its a tricky move, though, because too much blood thinner can cause a patient to bleed internally and possibly die. To gauge the best doses, many physicians are going off of a patients D-dimer levels, which is a biomarker for the presence of blood clots. New clinical trials have quickly spun up (including a multi-state one in the US to test one type of powerful blood thinners, known as tPA (tissue plasminogen activator) in Covid-19 patients, as STAT News reports). And Bikdeli and others have formed an international collective to provide interim consensus-based guidance, he says. What is needed most is high-quality data.

But these preventive treatments wont help those whove had strokes or other major blood-clot complications before receiving medical care. And that number, though still small, is real, as the five young stroke victims from New York City show.

The New England Journal of Medicine report included all stroke patients under 50 at the Mount Sinai health system in New York City during a two-week period in late March and early April. That this rate was nearly seven times the number of stroke patients in that age group during any average two-week period over the previous year indicates a very strong correlation between Covid-19 even mild and asymptomatic cases and the potential for major blood-clotting.

These patients were at home with mild or no symptoms who suddenly developed signs of stroke, Oxley says.

Some of these young patients had also been reluctant to seek medical attention even after fairly severe stroke symptoms. And it wasnt unreasonable for them not to be on the lookout for such a major neurological issue. These are people among the least likely statistically to have a stroke, J Mocco, a Mount Sinai neurosurgeon and coauthor of the report, told the Washington Post.

For example, the youngest, a 33-year-old woman, developed slurred speech and felt weak and numb on her left side for 28 hours before seeking help. She (as well as one other stroke patient in the study) was concerned about going to a hospital during the pandemic, the authors noted even though she had had a cough, headache, and chills for a week.

She is one of the lucky ones. She is the only one who has been able to start speaking again. After 10 days in the hospital to treat her blood clotting, she was discharged to a rehabilitation center.

There is also a question of how long the danger of Covid-19-related clotting lasts. Laurence notes that a lot of our cases, they went through their cough and fever, then all of a sudden, theres a stroke or a blood clot in their legs. For other patients, after having recovered from their primary Covid-19 symptoms, their difficulty of breathing came back, signaling that they have a pulmonary embolism in their lungs, he says. So people have to be vigilant to look for possible signs even after they feel like they have passed the worst of their illness.

Additionally, people at high risk for thrombotic events need to be vigilant, keep good hydration, and keep being active, especially during the period of social distancing and lockdown, Bikdeli says. This group includes people with a family history of blood clots or strokes, obesity, some cancer treatments and surgeries, pregnancy, some birth control methods, and others.

But major strokes can be treatable, Oxley notes. Its just a question of timing. For best results treatment must begin within six hours of stroke. As he told the Washington Post, the message we are trying to get out is if you have symptoms of stroke, you need to call the ambulance.

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Stroke and coronavirus: Blood clotting is a new Covid-19 mystery - Vox.com