Doctors treating the sickest Covid-19 patients have zeroed in on a new phenomenon: Some people have developed widespread blood clots, their lungs peppered with tiny blockages that prevent oxygen from pumping into the bloodstream and body.

A number of doctors are now trying to blast those clots with tPA, or tissue plasminogen activator, an antithrombotic drug typically reserved for treating strokes and heart attacks. Other doctors are eyeing the blood thinner heparin as a potential way to prevent clotting before it starts.

Without a rigorous study, though, it’s impossible to know the potential risks or benefits of tPA, blood thinners, or other drugs — or what makes a difference. Until more robust research gets underway, the body of evidence now is a handful of case reports and anecdotal observations on the use of drugs to combat clots.

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“I can’t stress enough that it is important to have a controlled study to demonstrate that people who get this either do or don’t do better,” said Christopher Barrett, a senior surgical resident at Beth Israel Deaconess Medical Center, a research fellow at MIT and co-author of case reports recently published on blood clots in Covid-19 patients.

As with so much else about the Covid-19 response, health experts are learning about the symptom on the fly. Blood clots are common in patients who are immobilized, but they seem to be smaller and cause far more severe damage in some Covid-19 patients. Doctors have said they see patients with blood clots forming not only in their lungs, but also in blood vessels. Autopsies have also revealed blood clots in kidneys and other organs, which some experts say suggests an overwhelming immune system response to the virus that inflicts harm on the body.

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Physicians from the U.S., the Netherlands, and China have published a number of case reports in scientific journals about Covid-19 patients with a multitude of small blood clots. In one report, researchers in China said 7 out of 10 patients who died of Covid-19 had small blood clots throughout the bloodstream, compared to fewer than 1 in 100 people who survived. Some of the patients in those case reports received blood thinners or tPA, sometimes when there seemed to be nothing else to try. Some survived, some did not.

“This is a real-time learning experience,” said Clyde Yancy, chief of cardiology at Northwestern University Feinberg School of Medicine.

“I don’t think any of us can declare anything definitively, but we know from the best available data that about one-third of patients who have Covid-19 infections do in fact have evidence of thrombotic disease,” he added. Yancy said there is early-stage, preliminary evidence to suggest that a regimen of anti-coagulants used as a preventive tool could reduce the number of clotting episodes a patient experiences.

It still isn’t clear why the virus leads to these blood clots forming, or why patients’ bodies can’t break them up. It also isn’t clear how significant a role they play in a patient’s illness. Those questions will take time to answer, Barrett said.

But there remains a need for treatments that can buy time to help people fight the virus.

“It’s not necessarily the virus killing people, it’s the organ failure that happens as a result of the viral infection,” Barrett said. “If you can support people through their organ failure, … the immune system will eventually clear out the virus.”

The three patients in Barrett’s case reports, all of whom were on ventilators to help them breathe, initially did better when they were given tPA in what’s known as off-label use in salvage therapy. One of them died, one of them improved briefly, and one of them had a durable response, he said.

Barrett is part of a group awaiting approval from the Food and Drug Administration to move forward with a randomized clinical trial to determine what if any role tPA might play. The trial they hope to conduct at three hospitals in Colorado, one in Massachusetts, and one in New York will give people the drug when they are not as sick as the people in the case reports, who had exhausted all other treatments. Patients will be randomly assigned to receive the drug or a placebo; the trial will also test different dosing.

“We really need the data to prove or disprove that it’s working.”

Hunter Moore, transplant surgery fellow at University of Colorado, Denver

“Until then, we’re kind of handicapped,” said Hunter Moore, a transplant surgery fellow at the University of Colorado, Denver, and a researcher working on the trial with Barrett. Now, he said, “it’s all based on off-label use and it’s kind of hearsay in terms of how it’s done. So we really need the data to prove or disprove that it’s working.”

Doctors around the country are already giving patients heparin or tPA. Many reached out to Moore and Barrett after reading their case reports, hoping to try tPA on their own patients. At Mount Sinai Hospital in New York, five patients were given tPA, with mixed results, according to an Associated Press story that sparked strong reactions among some. Former FDA Commissioner Scott Gottlieb has called for more comprehensive research on the subject — which Moore and Barrett’s proposed study could provide.

The drug tPA does carry its own risk. It’s typically given to stroke patients within hours of symptoms to reduce the risk of bleeding in the brain. But Moore pointed out that the risk of those bleeds for patients on tPA is lower than for Covid-19 patients who are placed on ECMO machines to improve oxygen levels in their blood.

Yancy of Northwestern said any studies on blood clots will contribute to the picture of how cardiovascular conditions heighten the danger of Covid-19 infections. That, too, could shed light on the disproportionate burden on African Americans, whose infection rate is threefold higher than other Americans’ and whose death rate is sixfold higher.

Risk factors for Covid-19 infection such as hypertension, diabetes, obesity, and preexisting cardiovascular disease — all of which are more common in African Americans — tip the scales toward more serious illness. Socioeconomic factors that make it harder for some people to work from home also likely play a part. Blood clotting may be one more key factor.

“The reason for the increased infection rate likely has very little to do with race [but] more to do with the life and living circumstances for African Americans,” Yancy said.

  • It appears that blood thinners are an important early treatment modality unless there are plausible contraindications.

  • Along with being an antiviral, Carbon60 hydrated fullerenes breaks up blood clots..Carbon 60 hydrated fullerenes breaks up blood clots

    The Acceleration of Blood Plasma Clot Lysis in the Presence of Hydrated C60 Fullerene Nanostructures in Super-Small Concentration
    April 2010Fullerenes Nanotubes and Carbon Nanostructures Nanotubes(3):303-311
    DOI: 10.1080/15363831003785257
    G. V. AndrievskyG. V. AndrievskyD. ShakhninA. TronzaShow all 5 authorsА. A. TykhomyrovА. A. Tykhomyrov

    Abstract
    There are no systematic data about the influence of chemically nonmodified fullerenes on key enzymes of organism, in particular, proteases of haemostasis system. In this study we describe preliminary in vitro data indicating the essential acceleration of blood plasma clot cleavage in the presence of nanostructures of hydrated C60 fullerene (C60HyFn). The super-small concentration of C60HyFn (10−12-10−14 M) applied in the experiment was comparable to that in which hydrated fullerene exhibits marked antioxidant and neuroprotective effects in vivo. The influence of C60HyFn on the kinetics of clot lysis, induced by tissue plasminogen activator (t-PA), has been explored in vitro. The incubation of t-PA samples in C60HyFn solution has increased the lysis rate 2.7 times and diminished the half-lysis time 1.6 times, compared with corresponding parameters for t-PA dissolved in distilled water. Taking in consideration that in this case C60 concentration (in mol) was by 2–4 orders less than concentration of enzymes participating in fibrinolysis, it has been concluded that biological activity of super-small C60HyFn concentrations (doses) was not directly related to the biological properties of C60 fullerene molecule itself but was mediated by specific and ordered water structures which C60 molecule organizes round itself. Also, we have suggested that the activation of fibrinolysis may occur due to the stabilization/protection of active conformation of protease molecules in the presence of specific water structures ordered by C60HyFn. Applications of hydrated fullerenes can be a perspective approach for both usage of thrombolytic enzymes and for design of novel anticoagulants.

  • This may mean that those already on blood thinners (with already thinner blood) are actually safer ? If Covid is causing blood complications, then have any links been found between level of Covid illness severity / mortality – and blood type?

  • If prior medical history of Covid-patients became standard analysis, these type of medical links would become much clearer, not just discovered “by happenstance”. THIS is what the data techs need to dig into, hard and fast. It’s easy to give everyone being tested a form to complete (return by mail, email etc) on their medical history and important habits such as smoking. That this has not yet been standardized is beyond me.

  • It was reported that an MD in Italy wrote that 9 out 10 deaths in his area were caused by generalised venous thromboembolism and not pneumonia.
    This was revealed by autopsies.
    · at the Sacco hospital, they give Clexan to everyone, with predictive D-dimero: the higher the patient will respond.
    · at the San Gerardo of Monza Clexane and cortisone
    · at the Sant’Orsola in Bologna Clexane to everybody – protocol shared with family doctors who prescribe Plaquenil a go-go, on all monosymptomatic patients at home

  • Chloroquine is used to treat patients with Lupus, for clotting disorders, specifically those with antiphospholipid antibodies or antiphospholipid syndrome.

    Antiphospholipid antibodies/syndrome is found in patients with Covid 19. These clots are impacting all organ systems for those who are severely ill. Read up on this syndrome especially as it relates to the lungs. (Fever, dry cough, difficulty breathing.. and quick decompensation for some).

    It seems as though there is a link?

    As a healthcare provider, it makes sense to try and prevent the formation of clots in the early stages.

  • It would seem that a daily dose of something like Eliquis could combat the potential, or at least help minimize the effects of the blood clots. Am I just using too much common sense or is this already being discussed.

    Point is, if I contract the virus my first call will be to my Pulmonologist in an effort to double my daily dose.

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