COVID-19 leads to blood clots in a significant number of people who have a severe form of the disease. In an interview with Medical News Today, thrombosis expert Prof. Beverley Hunt explains why blood clots are dangerous for those with the new coronavirus.
As news of a SARS-CoV-2, the new coronavirus, traveled across the globe, many experts thought that they would primarily encounter respiratory symptoms.
And little did we expect to be hearing about cardiovascular complications, digestive symptoms, the loss of smell and taste, and the likes of “COVID toe,” one of a collection of skin symptoms that some people with COVID-19 develop.
Blood clots are another complication that has been making headlines. MNT reported on a series of articles in the journal Radiology that suggested that a significant number of people with severe COVID-19 develop life threatening clotting.
But why would a virus that primarily infects the respiratory tract cause blood clots? And how is this putting patients at serious risk?
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Prof. Beverley Hunt is the medical director of the British charity Thrombosis UK, as well as chair of the steering group for World Thrombosis Day. She is a professor of thrombosis and hemostasis and works for the United Kingdom’s National Health Service (NHS) in London.
Prof. Hunt told MNT about the biology of blood clotting, her surprise at how the new coronavirus changes the properties of the blood in those with severe disease, and why we should keep moving, even during lockdown, to reduce our risk of thrombosis.
‘The conductor of the blood clotting orchestra’
MNT: How do blood clots form, and why are they potentially dangerous?
Prof. Hunt: In 1846, the German pathologist [Rudolf] Virchow described three things that predispose people to venous thrombosis.
They are: changes in the flow of the blood, changes in the stickiness of the blood — although he didn’t use the word “sticky” then — and changes in the blood vessel wall.
Of these, probably the most important one for the average member of the public is flow. Just sitting here for 90 minutes without moving my legs, blood flow crashes. It drops by about 50%.
When you walk, every time your muscles contract, they squeeze the veins and push the blood back up toward the heart.
There isn’t a natural muscular system within the veins, unlike within the arteries. We’re totally dependent on movement to keep the flow going.
This is a major risk factor for hospital patients, for someone who is sick, but also for anyone sitting for long periods of time.
As far as the stickiness is concerned, we are talking about changes in the blood proteins. The commonest cause of these changes is being ill.
If you’re ill, you produce chemical cytokines that tell the liver to make more clotting proteins. Then your blood is full of clotting proteins that make it very sticky and very ready to clot.
The last thing is the lining of the blood vessel. It’s very susceptible to hormones, particularly in people who are ill and people who take hormone replacement therapy. Those cytokines make it much, much more liable to form a clot.
When we come to COVID-19, we know that the new coronavirus can enter the lining of the blood vessels. The new coronavirus behaves in some way like the conductor of the blood clotting orchestra.
‘I’ve never seen such sticky blood’
MNT: Were you expecting to see such a big problem with blood clots in people with COVID-19?
Prof. Hunt: The issue with COVID-19 is that the blood is incredibly sticky.
We are seeing people in hospital with pneumonia. They are in hospital because they are short of oxygen, and they need extra oxygen. That’s really why they are coming in.
We know that most people who get COVID-19 get better in about 7–10 days, and we have about 5% who develop pneumonia.
Their immune system is reacting very strongly to the pneumonia, and the lungs are full of immune cells that produce cytokines. In turn, these tell the liver to make clotting proteins. The inflammatory mechanism leads to what we call a “prothrombotic state.”
Let me give you an example. The main clotting protein in the blood is fibrinogen. It’s soluble, and you have 2–4 grams per liter in your blood.
The clotting factors switch soluble fibrinogen to insoluble fibrin, and that is the clot.
The level is 2–4 grams per liter in most people. If you are pregnant, or as you get older, the levels get higher. They might go up to 5, 6, or even 7 [grams per liter].
But what are we seeing in COVID-19? We are seeing levels of 10, even 14 grams per liter. I’ve been in this game forever, for decades, and I’ve never seen such sticky blood.
We know that all the other clotting proteins are similarly increased.
Inflammation and thrombosis
Prof. Hunt: I haven’t seen these values before in this many patients. Occasionally, you get a patient who has really high levels. But all of them have these really high levels. That is a major issue.
But we didn’t know that this was going to happen until the patients arrived. The initial reports from China, which we had a little bit of, suggested there were major clotting problems, but they called it something else, and I think they didn’t quite get it right in those early stages.
Now we know that these patients have incredibly sticky blood. This stickiness is causing them to have deep vein thrombosis. And of course, if you have a deep vein thrombosis, bits of it can break off and travel through your body and block some of the blood supply to the lungs.
And because the lungs aren’t working properly in the first place, this really isn’t a good thing in a really sick patient.
So, we are giving all of the COVID-19 patients small doses of blood thinners to reduce the risk. But really, the question is, should we be giving them more?
We know that the doses that we give under normal circumstances have minimal bleed risk. Their advantage is that the risk of blood clots is reduced by 50%. But should we perhaps be giving these patients a little bit more because their blood is so sticky? That’s currently the big research question.
The other thing that we’re seeing, which caught a lot of people out, is blockages in tiny vessels. Normally, if you do imaging of the lungs and you look for blockages in the blood vessels — with a pulmonary embolism, you typically see blockages in a few of the big ones.
What we are also seeing are blockages of tiny little vessels, in what we call subsegmental branches of the pulmonary artery. That’s not really a pulmonary embolism.
When we look at the postmortem reports from Chinese studies and from other studies out there, from the United States, Argentina, and Italy, we know that if there is really profound inflammation in an area, that can lead to thrombosis.
There is so much inflammation in the lung, and then we see small pockets of thrombosis caused by inflammation.
The problem is that — I don’t think we are preventing this with the small doses of blood thinners. This is all about inflammation being so marked that we need to deal with it first. The current clinical trials are looking at reducing the viral load and addressing inflammation.
I think if we had less inflammation, we would see less of the clotting in the tiny blood vessels.
Blood thinners and mortality
MNT: Do you need to look at a multidisciplinary approach, then, to reduce the effect of the virus, dampen inflammation, and limit clotting?
Prof. Hunt: At the moment, we know that we can give patients oxygen. We also give everyone small doses of blood thinners, and we know that will reduce their thrombotic risk.
But we don’t have an effective antiviral, and we don’t have data on the anti-inflammatories yet.
We are just starting a trial to see if giving bigger doses of blood thinners will improve outcomes in these patients.
MNT: Are the patients who receive the small doses of blood thinners doing better than those who may not be receiving these elsewhere?
Prof. Hunt: I campaigned for years to make sure that NHS England gives effective blood thinners to all the patients at risk in hospitals.
In fact, NHS England is the world leader in preventing hospital-acquired venous thromboembolism or hospital-acquired thrombosis.
In our system, everybody has to have a risk assessment when they arrive at a hospital, and they get blood thinners if they are at risk.
We did this for the COVID-19 patients right from the start, so we don’t have comparative data.
But interestingly, looking at the Chinese data from Wuhan, they do not routinely use blood thinners. [But] they gave a small proportion of the patients blood thinners, and they showed that they had lower mortality.
Stay mobile to reduce blood clot risk
MNT: Blood clots are not an early sign of COVID-19, then? They are a knock-on effect of the viral infection and the subsequent inflammation?
Prof. Hunt: That’s right. There is one proviso, though. During lockdown, a lot of people aren’t moving around very much.
If someone is working at their desk, really, they should be getting up every hour or 90 minutes to move around a little, so that their blood is squeezed up and moved around, and they are not increasing their risk of having a clot.
This is called seated immobility syndrome, and under this, we would include people who sit for long times at their desks, on airplanes, or on long journeys in busses or cars.
It’s really important to keep mobile. Also, remember to eat well. Don’t get dehydrated, because dehydration is a risk factor for developing clots.
But the main thing is mobility. This is really important if you’re at home in some form of lockdown.
MNT: What research do you think is important to focus on going forward?
Prof. Hunt: With COVID-19, we need to look at the whole patient journey. If you already have some level of sticky blood, which 6% of the population do, then we might think about giving you a blood thinner, just in case you develop pneumonia.
This means we need research in ambulatory care to prevent these issues, in case people go on to have pneumonia.
For those patients who do go on to the hospital, they get blood thinners there. Then we discharge them. But, they still have really sticky blood. We know that if we look at hospital-acquired venous thromboembolism, the risk extends right out to 90 days post-discharge. In fact, 60% of clots actually occur after discharge.
We need to think about giving these patients blood thinners after they go home. We do not normally do this in what we call “medical patients,” patients who haven’t had surgery.
But there is a recommendation coming out from NHS England that we should be doing exactly that, and most centers are now giving patients blood thinners for 2 weeks after their discharge to reduce the risk of clots.
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