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The Latest Medical Findings Suggest Blood Clotting In COVID-19

6 months ago

4800  0
Posted on Apr 28, 2020, 3 p.m.

Another mysterious and deadly complication that appears to be showing up in the front lines fighting the outbreak of COVID-19 is blood flow impeded by blood clots; the thrombotic events are occurring for a variety of reasons among those in intensive care, but the rates among COVID-19 patients are substantially higher than would otherwise be expected. 

"I have had 40-year-olds in my ICU who have clots in their fingers that look like they'll lose the finger, but there's no other reason to lose the finger than the virus," Shari Brosnahan, a critical care doctor at NYU Langone told AFP.

After spending 3 weeks in an ICU with COVID-19 actor Nick Cordero’s doctors were forced to amputate his left leg. Another patient at NYU is suffering from lack of blood flow to both feet and hands and an amputation may be required or the blood vessels may become so damaged the extremity could fall off by itself. 

Blood clots are not only dangerous to limbs they can also find their way to the lungs, heart, or brain to cause lethal pulmonary embolisms, stroke, or heart attack. A recent study from the Netherlands published in the journal Thrombosis Research indicates that 31% of 184 COVID-19 patients suffered thrombotic complications. 

Another study published in the Journal of The American College of Cardiology found the risk of thrombotic complications to be so great that COVID-19 patients “may need to receive blood thinners, preventively, prophylactically," even before imaging tests are ordered, said Behnood Bikdeli who is a doctor at New York–Presbyterian Hospital.

Although it is not known exactly why this is happening there are several explanations such as those with severe forms of COVID-19 with underlying medical conditions such as heart or lung disease are linked to higher rates of clotting even without being infected. Also being in an ICU can make a person more likely to develop a clot as they are remaining still for too long. Infection with COVID-19 is associated with an abnormal cytokine storm immune reaction that research indicates is also linked to higher rates of blood clotting. 

Something about the COVID-19 virus itself may be causing coagulation, which does have some precedent in other viral illnesses. A study published in the journal The Lancet shows that the virus can infect the inner layer of organs and of blood vessel endothelium, which could in theory interfere with the clotting process. 

Brosnahan suggests that thinners may be effective in some COVID-19 patients but they may not work for all patients because the clots may be too small at times. "There are too many microclots," she said. "We're not sure exactly where they are." In fact, autopsies have shown some people’s lungs, bowels, livers, and kidneys who have lost their battle with the virus to be filled with hundreds of microclots.

Hooman Poor, MD, a pulmonologist and critical care specialist at Mount Sinai Hospital in New York City, has been studying lab results of COVID-19 patients and found that many have high levels of D-dimer protein pieces, which are left over when the body breaks up blood clots, he believes that many patient’s bodies are trying desperately but failing to clear blood clots. 

Around the globe those caring for COVID-19 patients are finding that when they draw blood it clots in the tubes, when catheters are inserted for kidney dialysis and IV line to draw blood the tubes quickly become clogged with clots. 

"Patients are making clots all over the place," says Adam Cuker, MD, a hematologist and associate professor of medicine at the Hospital of the University of Pennsylvania. "That's making management of these patients very challenging."

Sharon Fox, MD, PhD a pathologist at Louisiana State University Health in New Orleans has been conducting autopsies on those who have lost their battle with COVID-19, so far they share something in common, they are riddled with blood clots in the smallest vessels of the body, especially the lungs where there these tiny clots appear to have cut of blood flow to the small air sacs where blood cells would be exchanging oxygen and carbon dioxide. 

“I've never had a series of cases like this, where they all look the same, and all of the lungs have a similar pattern. There are types of vascular injury at autopsy that I haven't seen before. I would say it's new," says Fox, adding that the pattern of damage is striking. "There's no ability for the blood to flow through and exchange oxygen like it should," she says.

“We still need more controlled data, but based on clinical observations and the few studies that have been published, it looks like thrombosis [blood clotting] is more common in these patients," Cuker says.

This new mystery may help to solve the slightly older one, as lungs that are filled with microclots may explain why ventilators work so poorly for patients with low blood oxygen. Earlier into this outbreak doctors were treating patients with protocols developed for wet lungs, but in some cases it may not be due to the lungs being occupied with water, rather it may be that microclotting is blocking circulation and blood is leaving the lungs with less oxygen than it should. 

"While we react surprised, we shouldn't be as surprised as we were. Viruses tend to do weird things," said Brosnahan, and while the array of complications may seem daunting, "it's possible there'll be one or a couple of unifying mechanisms that describe how this damage happens," she said. "It's possible it's all the same thing, and that there'll be the same solution."

Another study published in the Lancet has reported evidence of viral bodies of this novel coronavirus invading endothelial cells, which is the lining of our blood vessels that directs important functions of the vascular system, like clotting and swelling. Co-author Mandeep Mehra, MD, medical director of the Brigham and Women's Heart and Vascular Center in Boston suggests this virus can directly infect the endothelium, "This is actually a disease of the endothelium," he says.

Mehra thinks the infection only begins in the lungs because breathing is the easiest entry, once infected lungs cells begin to be destroyed and the virus then travels into the bloodstream where it infects endothelial cells causing endotheliitis. This comes from not only the direct infection but also from the cytokine storm that was launched to fight it off. Mehra believes his theory of infection may explain some of the puzzle to COVID-19. 

This theory may explain why those with certain conditions are also the ones who get the sickest when infected, and it may help to explain why those with low blood oxygen may not have lungs as stiff as they would be in others with respiratory distress or pneumonia. One of the consequences to endotheliitis is the blood vessels are not able to constrict as normal. When a part of the lungs becomes damaged blood vessels in that area close off so that blood will flow to a part of the lung that is still working. This is to protect the body from a sudden oxygen drop, this system appears to break down with COVID-19 infection, and Mehra believes infection of the endothelium is to blame. 

According to Mehra this clotting is a feature of COVID-19, when it becomes the biggest problem the disease has advanced to become very severe, for this reason treating the resulting blood clots may not work, and may explain why ventilators are not helping more patients. One study in New York City hospitals estimates that of 5,700 patitens 12% needed a ventilator but 88% of those died. 

“It's not acting like influenza or other bacteria pneumonia where you get inflammation in the lungs and fluid buildup and very stiff lungs. That doesn't seem to be the case, at least early on," Poor says. "The virus is acting as if its primary target is the endothelium," he says.

These clots may explain part of the mystery, but the clots themselves are just another part of a much larger problem, one that hopefully doctors can solve soon.

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