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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.”