Treating
Covid-19 patients with medicines to prevent blood clots might help
reduce deaths in patients on ventilators, based on new observational
data.
A team from Mount Sinai Health System in New York on Wednesday
reported better results for hospitalized Covid-19 patients who received
anticoagulant drugs compared to patients who didn’t. The data are
preliminary and require confirmation in larger studies with a more
robust design, the authors say about their
study published in the Journal of the American College of Cardiology, but their findings add weight to medical guidelines.
While there are no firm data on the frequency of clotting problems in
Covid-19 patients, there have been troubling anecdotal reports of
patients whose lungs are peppered with tiny clots or who have suffered
strokes.
Last month,
other Mount Sinai doctors detailed strokes in five Covid-19 patients in
their 30s and 40s, an unusually young age for such a damaging
cardiovascular event. Other reports of strokes have bubbled up
elsewhere, including 88 patients in the original epicenter of the
coronavirus in
Wuhan, China, six in
London, and three in
Strasbourg, France.
Autopsies of 12 Covid-19 patients showed strong evidence for blood
clotting problems, including clots in the lungs and in the legs, a group
in
Hamburg, Germany, reported Wednesday. In all 12 cases, the cause of death was found within the lungs or the pulmonary vascular system.
Together they add to accumulating evidence that Covid-19 leads to
abnormal blood clotting and that anticoagulant medications might help.
The most recent Mount Sinai study analyzed data from more than 2,700
patients hospitalized for Covid-19. The percentage of patients who died
while not on a ventilator to help them breathe was about the same,
whether or not they received some form of anticoagulant. Time to death
was a week longer for those who were given anticoagulants: a median of
21 days compared to 14 days for those who did not receive
anticoagulants.
There was a mortality difference among sicker patients who were on
ventilators in intensive care units: 63% of those given anticoagulants
survived versus 29% who did not get anticoagulants. The patients were
not randomly assigned to treatment or no treatment, however, meaning the
study could not rule out other explanations for the apparent survival
benefit.
Bleeding is a risk for patients who take anticoagulants, but the
study found no significant difference between patients who did or did
not receive anticoagulants.
“They interrogated their database of Covid-19 patients and came up
with an interesting, thought-provoking finding that patients [on
ventilators] who received full-dose, systemic anticoagulants had a lower
mortality than those who did not, particularly patients in the
intensive care unit,” said Jeffrey Weitz, president-elect of the
International Society on Thrombosis and Haemostasis and a
physician-scientist at McMaster University in Canada who was not
involved in the study. “What it suggests to me is that anticoagulation
alone might attenuate the disease, but it may not be the answer. We need
more data and longer follow-up. Remember, this is just observational
data. We don’t have a full picture on all of those patients.”
Based on the data in hand, Mount Sinai has changed its guidance on
anticoagulants, said Valentin Fuster, a co-author of the study and
physician-in-chief at Mount Sinai Hospital. Doctors had been giving
patients anticoagulants before, using their clinical judgment. “We
developed a new policy once we got these results,” Fuster said. “And
that is to increase the dose of anticoagulants to the patients with
Covid-19.”
Current
guidelines
from the American College of Cardiology for managing abnormal blood
clotting in Covid-19 patients note that while most of its expert panel
members recommend preventive doses of anticoagulants, a minority say
they use the higher doses typically prescribed for patients with
established blood-clotting problems. McMaster’s Weitz is a co-author of
those guidelines.
“What we’re really trying to find out is who should get it and how much,” he said about anticoagulant medication.
Anu Lala, another co-author and a cardiologist at Mount Sinai, said
while the data reflect what she’s been seeing in the hospital, they
demand more study.
“The very fact that there is a signal there is in line with what we
seem to be observing clinically, having been on the wards for four
weeks,” she said. “It opens the gate for us to do a deeper dive. There’s
a lot more work to be done to prove or even really determine causality
One unknown: Did patients have an underlying cause for blood clots,
such as the abnormal heart rhythm atrial fibrillation? Patients had
their blood drawn when they were admitted to one of the five hospitals
in the Mount Sinai system, and if they had inflammatory markers, they
were put on oral, injected, or infused anticoagulants. Higher doses were
given in the ICU.
In the earlier case reports on young Covid-19 patients who had
strokes, there were no signs of blood-clotting disorders. J Mocco, a
neurosurgeon at Mount Sinai, said that right when New York was seeing a
surge in hospital admissions for Covid-19, he and colleagues in
cardiology and pulmonology noticed a much higher than expected number of
patients with stroke, amounting to a sevenfold increase over normal
numbers. These patients were 15 years younger than typical stroke
patients and they didn’t have risk factors for stroke such as irregular
heartbeats or heart failure.
“I don’t want every person out there being petrified they’re going to
have a stroke because of the coronavirus being out there,” he said.
“But within this group of individuals, it does strongly suggest that the
virus is contributory to their strokes.”
That argues for starting blood thinners sooner and looking at other
measures, he said. “In some patients, we’re even trying clot-busting
drugs to try to undo some of the clotting.”
Why Covid-19 patients have abnormal blood clotting isn’t known, but
doctors suspect it’s related to inflammation and the ACE2 receptors the
coronavirus latches onto, not only in the lungs and other organs but
also on the lining of blood vessels. Inflammation and blood clotting
normally go together, with a blood clot forming around the site of an
infection. How this goes wrong in Covid-19 and whether it’s just one
factor is still not understood.
At Mount Sinai, the next step is another observational study of 5,000
Covid-19 patients taking blood thinners to home in on why they were
started on anticoagulants, followed by a randomized clinical trial based
on what is learned.
“The more we learn, I think, the more we’re humbled, quite frankly,” Lala said. “We’ve got to keep going.”
Giving blood thinners to severely ill Covid-19 patients is gaining ground
