Why Coronavirus patients are dying – So what exactly are blood clots, and why are they so dangerous? Blood clots, don’t normally form in the body….unless we have we have bleeding, for example if we cut our finger.
That’s how we heal, right? The clot stops further bleeding. But sometimes, some people form clots when they are not suppose to.
Our blood, besides being mostly water, is made up of a bunch of different proteins with different carbohydrates and fats, and these different chemicals interact with each other, and all it takes is one piece of the puzzle to be missing, or abnormal, to totally throw off the balance of either clotting too much, or not clotting enough. For example, in Hemophilia B, these patients are missing a protein called factor IX, and that’s why they bleed more than they should.
But some people could have the OPPOSITE problem, where they clot too easily, and form unwanted blood clots, which is what happens with antiphospholipid antibody syndrome, and that’s why these patients need to be on a blood thinner. So antiphospholipid antibody syndrome is not only a mouthful, but it’s a pain in the ass because it has a tendency to cause clots in both veins and arteries.
But guess what, its not the only cause of abnormal clotting, as there are hundreds of other medical conditions that can do the same thing. Such as Factor V Leiden and Prothrombin gene mutation, or antithrombin deficiency, or protein C and protein S deficiency.
Regardless of the cause, when blood clots do form, they are most commonly in the deep veins of our legs and sometimes arms, although they can form anywhere in our blood vessels. When blood clots form in our deep veins, its called deep vein thrombosis, and the most common symptoms are swelling, and pain.
DVT is dangerous because it can break off, and travel to the heart and lungs, and this is called a pulmonary embolism, which can be fatal. And there are plenty of people who die every year, from pulmonary emboli. Sometimes the clot is so big that it causes death within minutes.
Thankfully not everyone who gets a blood clot in their lung dies. The most common symptoms of pulmonary emboli are shortness of breath, chest pain, and sometimes cough. They can also have lightheadedness and dizziness, or even temporarily lose consciousness. And some people don’t have any symptoms. It usually depends on the size of the clot.
Sometimes, clots can form in the arteries, and cause a stroke. Or if they can lodge in the coronary arteries, and cause a myocardial infarction, aka a heart attack.
Or they can cut off blood flow to a leg. And there are more reports of patients presenting to the hospital, not with typical COVID-19 symptoms, but symptoms pulmonary emboli.
So are blood clots at least part of the reason why some people with COVID-19 are dying?
I can tell you that the number of clotting problems my colleagues are seeing in the ICU across the country, all related to Covid-19, is unprecedented. But this isn’t just a bunch of doctors and nurses that I know who are reporting this. A recent Dutch study found that of the 184 patients in the ICU with Covid-19 pneumonia, 20% were having clotting issues.
There was also a similar study in Wuhan, China where 25% of hospitalized COVID patients had clots. Why, and how is SARS-CoV-2, which invades the cells of the lungs, specifically they type II alveoli, how is it causing blood clots to form in the body? When someone has a severe case of COVID-19, it’s causing a ton of inflammation within the lungs. This inflammation is what is triggering the blood clots to develop.
We knew that this happens with ARDS even before COVID-19 came around. In ARDS, these patients usually develop microthrombi, meaning tiny clots, that form in the tiny blood vessels in the lungs. And these microthrombi can combine to form bigger thrombi, meaning bigger clots.
This happens at least partly because of the cytokine storm that develops as a result of the infection. Blood clots are also a concern with seriously ill people in general, regardless of what illness they have, because these patients aren’t moving much, if at all, and lack of movement further predisposes one to having clots.
And that’s why when patients are admitted to an intensive care unit, we usually have given them blood thinners, unless there is a reason not to, for example, if they have to bleed, we don’t want to give those patients blood thinners. But when we give these blood thinners, we give them in prophylactic doses, meaning the intention is to reduce their risk of developing a clot in the first place.
But these prophylactic doses are considered low dose. And the chances of someone having severe bleeding from these small doses are very small. But the blood clots with COVID-19, these are just a whole ‘other beast.
There’s something more going on here. So how, and why is COVID-19 causing more blood clots than usual?
Long story short, the virus enters the alveolar cells in the lungs using the ACE2 receptor, and once it does that, it causes the cell to have less ACE2 receptor on its surface. This increases the amount of 3 things within the lungs: 1) inflammation 2) formation of clots and 3) constriction of blood vessels going to the lungs, meaning pulmonary vasoconstriction.
And guess what, each and every one of these things by itself can lead to low oxygen levels. So you can imagine what that means when you have all 3 of these things going on at the same time. The way that oxygen gets into our blood from the alveoli, it has to diffuse from the alveoli to our capillaries.
The cytokine storm causes destruction of the alveolus and the endothelium, and this, this my friends, is a trigger for clotting. We knew this happens in ARDS even before COVID. But guess what, the virus that causes covid can actually invade the cells here in the endothelium, because these cells have ACE2 receptors as well. And that can cause even more inflammation, and more clotting.
And these clots can combine with other clots, to form bigger clots, and can travel to other parts of the body. And in another published report in the NEJM, there were 3 patients in the ICU who had COVID-19, and these 3 patients developed blood clots that were significant enough to cause major blockages in blood vessels. These 3 patients were positive for antiphospholipid antibodies. These antibodies are not in the blood for the vast majority of people.
These antiphospholipid antibodies are bad because they attack phospholipid proteins in our body, and if severe enough, they can cause major clots to form in our blood vessels. Anti-phospholipid antibody syndrome is a condition that depends on someone’s genetics.
But these antibodies can also arise transiently in patients with critical illness and various infections.So do all patients with COVID-19 who have blood clots, do they all have this transient anti-phospholipid antibody syndrome?
We don’t know yet.
The cytokine storm that is triggered in the lungs, that can affect other organs in the body, such as the heart, kidneys, and brain. And as if that’s not bad enough, just about all of the other organs in the body have ACE2 receptors, such as the heart, kidneys, and brain.
So inside the body, COVID is causing a category 10 Hurricane in some people, about 3-4% of people who get the virus. So besides looking at drugs to treat the infection, we also have to consider giving the big doses of blood thinners to patients with severe disease, even if we are not able to diagnose them with clots.
Now some might say, well, doc, why cant you just diagnose them with clots?
Easier said than done, even during normal times. But its especially harder to do during this pandemic. Every test we do whether its an ultrasound of the legs looking for clots, whether it’s getting a CT scan of the lungs looking for a clot, of CT of the brain looking for stroke, all of these things requires more PPE, more potential exposure in the hospital, and sometimes more risk to the patient doing certain tests. And even if we do all these tests, if they come back negative, there is still the possibility of a false negative, because no test has 100% sensitivity and 100% specificity. In other words, no test is 100% accurate.
So there are going to be times, where you have a very sick patient with COVID-19 in the ICU, and you don’t know if they have blood clots. The question becomes, should you give them a high dose of blood thinner, meaning, should you treat them as if they have blood clots?
Not an easy question to answer.
Because the risk of life-threatening bleeding increases when you do so. Unfortunately, because this disease is so mysterious, and so new, with relatively few high-quality studies, doctors don’t have much to go on when it comes to treating these patients.
We will have to make difficult decisions, especially when it comes to giving a high dose of the blood thinner in the ICU. If we see that the patient has a blood clot, then the answer is easy, it gives them a blood thinner as long as they don’t have bleeding issues. But if we don’t see blood clots, it’s a difficult decision that will have to be made on a case-by-case basis.
Also, something a lot of people want to know, is there something you can do to reduce your risk of developing blood clots? The biggest thing that people, in general, can do, is to stay active. Meaning minimize your time sitting in a chair. That’s 1 factor that makes people more prone to developing clots.
So exercise is great. But if you cant do that, even walking around your room, or doing some stretching exercises, or even jumping jacks if you can. Other than that you want to take your doctor’s advice on what you should be doing to optimize your health.
Dr. Mike Hansen, MD
Internal Medicine | Pulmonary Disease | Critical Care Medicine
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