COVID-19: 'I’ve never seen such sticky blood’ says thrombosis expert
COVID-19: 'I’ve
never seen such sticky blood’ says thrombosis expert
COVID-19 leads to blood clots in a
significant number of people who have a severe form of the disease. In an
interview 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.TG 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?
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 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.
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.
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].
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.
Blood
thinners and mortality
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.
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
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.
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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