Covid 19 Blood Clotting issues

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Researchers Learning More About How The Coronavirus Sabotages Blood Vessels


10/25/20






LULU GARCIA-NAVARRO, HOST:

COVID-19 symptoms like strokes and kidney damage are unusual for a respiratory disease. Researchers are looking into how the coronavirus damages blood vessels and what that means for treatment.

Shortness of breath and a dry cough are often telltale signs of COVID-19. But even early on, doctors realized the virus can inflict all kinds of other damage, from strokes to strange rashes. What do these symptoms have in common? As Will Stone reports, many researchers are focused on how the coronavirus sabotages our blood vessels.

WILL STONE, BYLINE: Picture a skating rink before a hockey match. The top layer of ice is glassy and slick. The players and pucks glide smoothly across. Dr. William Li says that ice is like the lining of your blood vessels when you're healthy. But during a coronavirus infection...

WILLIAM LI: The virus damages the inside of the blood vessel and shreds the lining. That's like the ice after a hockey game.

STONE: The lining becomes ragged and leaky. Things start to get stuck.

LI: And you wind up actually having this situation which is really untenable for blood flow.

STONE: Li and an international team of researchers compared the lung tissue of people who died from COVID-19 with those who died from influenza. They found stark differences. For example, the COVID lungs had nine times as many tiny blood clots.

LI: The surprise was that this respiratory virus that gets into the lung makes a beeline for your vascular endothelial cells, the cells lining blood vessels.

STONE: These endothelial cells are a vital part of the vascular system, coating the inside wall of every artery, vein and capillary. If the novel coronavirus is wreaking a special kind of havoc on the endothelial cells, as Li and other scientists think, that helps explain why COVID complications can appear anywhere in the body.

LI: The effects in the brain, the blood clots in the lung and elsewhere and in the legs, the COVID toe, the problem with the kidneys and even the heart.

STONE: Early in the pandemic, Dr. Gaetano Santulli saw how many different organs could be affected, and he suspected endothelial cells might hold the key. Santulli's a researcher at Albert Einstein College of Medicine in New York City. He says, consider what these endothelial cells do in a healthy person.

GAETANO SANTULLI: Mainly the endothelial cell function are to avoid high blood pressure and to avoid blood clotting.

STONE: But when these cells don't work properly, when they're dysfunctional, the opposite can happen. Santulli saw this with COVID and realized...

SANTULLI: If there is endothelial dysfunction because of the virus, we can explain why we have an increased risk of blood clotting in COVID-19 patient.

STONE: Scientists aren't sure exactly how COVID damages blood vessels. What's clear is the body's immune response often begins to spiral out of control.

YOGEN KANTHI: What we see with the SARS-2 coronavirus is really an unprecedented level of inflammation in the bloodstream.

STONE: That's Dr. Yogen Kanthi of the National Institutes of Health.

KANTHI: We start to get this relentless, self-amplifying cycle of inflammation in the body. And that may lead to clotting.

STONE: This is most striking in severe cases of COVID. And doctors who care for these sick patients, like Roger Seheult, have come to see COVID as a vascular disease in addition to a respiratory illness. Seheult is a critical care and pulmonary physician in Southern California. Early in the pandemic, he noticed the patients who ended up in the ICU tended to have diabetes, high blood pressure or were obese. All those conditions can damage the blood vessels and cause inflammation. So if you catch the virus on top of that...

ROGER SEHEULT: It's a stress test. If you're right on the edge and you get the wind blown from this coronavirus, now you've gone over the edge.

STONE: And he also noticed that the patients hospitalized with COVID are different from those hospitalized for respiratory viruses like the flu.

SEHEULT: They are having shortness of breath, but we have to realize that the lungs is more than just the airways. It's an issue with the blood vessels themselves.

STONE: That's why COVID patients can struggle to get enough oxygen, even if air is being pumped into their lungs by a ventilator. Seheult says even after breathing improves, some patients still have damaged blood vessels.

SEHEULT: They're now off oxygen. They can be discharged home. But their vasculature is not yet completely resolved. They still have inflammation.

STONE: So what does this mean for COVID treatment? Doctors are already using drugs to manage inflammation and prevent clots, though they're still working out the best combinations and dosages. But they're also looking at more direct ways of protecting endothelial cells to prevent blood vessels from breaking down in the first place.

For NPR News, I'm Will Stone.
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Re: Covid 19 Blood Clotting issues

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Direct oral anticoagulant does not appear to offer protection against severe COVID-19

12/1/20


https://www.news-medical.net/news/20201 ... ID-19.aspx


DOAC (direct oral anticoagulant) pills are used in the treatment of atrial fibrillation by preventing blood clots. Even though blood clots are thought to contribute to complications from the new coronavirus infection, users of this class of drug do not seem to be protected against severe COVID-19, reports a large Swedish registry study from Karolinska Institutet published in The Journal of Internal Medicine.

Early during the ongoing pandemic, there were reports that many patients with severe COVID-19 had blood clots in their pulmonary arteries and other parts of the body.

" Our hypothesis was that blood clots per se could contribute to the severe functional deterioration of the lungs and other organs that is associated with COVID-19, so one would think that preventative treatment with anticoagulants would provide some protection."

- Benjamin Flam, doctoral student, Department of Physiology and Pharmacology, Karolinska Institutet, specialist doctor in anaesthesiology and intensive care, Karolinska University Hospital

Registry based study


No difference between the groups

The results of the observational study show that DOAC use did not reduce the rate of hospitalization, intensive care or fatality due to COVID-19.

"Our findings suggest that early DOAC treatment doesn't protect against severe COVID-19, but these should be treated with caution since there might remain differences between the groups that are difficult to measure," says Benjamin Flam. "Also, our study says nothing about whether other types of anticoagulants could be effective, but a good many clinical studies are being done around the world."

Source:


Karolinska Institutet

Journal reference:


Flam, B., et al (2020) Direct oral anticoagulant use and risk of severe COVID-19. Journal of Internal Medicine. doi.org/10.1111/joim.13205.
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Re: Covid 19 Blood Clotting issues

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Autoantibodies May Drive COVID-19 Blood Clots

2/2/21


https://jamanetwork.com/journals/jama/f ... le/2775690


In severe cases of coronavirus disease 2019 (COVID-19), patients may develop abnormal blood clots—from pulmonary embolisms in the lungs and deep vein thromboses in the legs, to clots that lead to strokes or heart attacks. A new study reveals that clot–promoting autoantibodies likely cause or contribute to these complications.

The research, published in Science Translational Medicine, draws from previous observations that found parallels between blood clotting abnormalities in patients with COVID-19 and those with an autoimmune clotting condition, antiphospholipid syndrome (APS).

“Early in the pandemic, we noticed many similarities between the coagulopathies of APS and COVID-19, especially the predilection for thrombosis in vascular beds of all sizes, from large arteries and veins to microscopic capillaries,” the study’s co–senior author Jason S. Knight, MD, PhD, associate professor of rheumatology at the University of Michigan, said in an interview.

Patients with APS produce autoantibodies to phospholipids and phospholipid-binding proteins. That led Knight and his colleagues to measure various antiphospholipid (aPL) antibody types in serum samples from 172 patients hospitalized with COVID-19. They detected the antibodies in 52% of samples using the manufacturer’s threshold and in 30% when they used a stricter cutoff.

Importantly, higher aPL antibody levels were associated with more severe respiratory disease, lower kidney function, and immune system hyperactivity, including the release of inflammatory cell remnants called neutrophil extracellular traps (NETs), which the team previously found were elevated in patients with COVID-19. Neutrophils release NETs—webs of chromatin, microbicidal proteins, and oxidant enzymes—to contain infections, but the traps can promote excessive inflammation and clotting when not properly regulated.

“[T]hese nascent observations sent us in hotter pursuit of a potential role for autoantibodies in COVID-19,” Knight said.

In laboratory experiments, neutrophils from healthy people overproduced NETs when cultured with autoantibodies from patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, similar to the response seen with aPL antibodies from patients with APS. Transferring the antibodies from patients to mice accelerated deep vein thromboses in 2 mouse models.

“Injections with antibody fractions from patients with severe COVID-19 drove thrombosis more aggressively than anything we have seen previously,” the study’s co–senior author, Yogen Kanthi, MD, who leads the vascular thrombosis and inflammation laboratory at the National Heart, Lung, and Blood Institute, said in an interview. “These experiments showed us that COVID-19 triggers the production of autoantibodies that can result in thrombosis.”

The research “is an important addition to our growing understanding of the complex multifactorial causes of hypercoagulability with SARS-CoV-2 infection,” Jerrold H. Levy, MD, a professor of anesthesiology, critical care, and surgery at Duke University Hospital, who was not involved with the study, noted by email. Whether these antibodies provide a therapeutic target or can be used to further define the degree of vascular injury and associated morbidity or mortality remains to be seen, he said. The antibodies also may help to identify patients with COVID-19 who are most likely to benefit from aggressive anticoagulation therapy, according Julio Chirinos, MD, PhD, associate professor of medicine at the University of Pennsylvania Perelman School of Medicine, who also was not involved with the study.

Blocking the NETs released in response to these autoantibodies could potentially prevent the cascade of events that produce clots in patients with COVID-19. Last year, Knight and Kanthi demonstrated that the antithrombotic medication dipyridamole blocks NET release in mice, supporting the medication’s potential as a treatment for APS. In the recent study, they found that the blood thinner also reduced NET release from neutrophils subjected to COVID-19 autoantibodies.

Dipyridamole is a safe, inexpensive antiplatelet medication that also has immunomodulatory and potentially antiviral properties. It stimulates “a robust antiviral type I interferon immune response, which we know to be suppressed in COVID-19,” Kanthi said. In a promising finding, researchers in China recently discovered that dipyridamole suppresses SARS-CoV-2 replication. Knight and Kanthi are now conducting a clinical trial to test its effectiveness among patients hospitalized with COVID-19 at the University of Michigan.

The recent study’s findings also have relevance for other potential COVID-19 treatment strategies. Plasmapheresis, for example, can improve outcomes among individuals with APS and may therefore benefit patients with COVID-19 who have high aPL antibody titers. Conversely, it’s possible that the transfer of convalescent plasma from COVID-19 survivors to severely ill patients could also transmit their clotting risk. Screening the plasma for prothrombotic autoantibodies could potentially improve the treatment, which has fallen short of expectations in clinical trials.

“We need to assess to what degree and for how long these antibodies persist in COVID-19 survivors,” Chirinos said by email. “This may have implications for longer-term thrombotic risk as well as for the treatment of COVID-19 patients with convalescent plasma.”
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Re: Covid 19 Blood Clotting issues

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Helping Patients with COVID-19 Avoid Blood Clots

Vascular experts are wading through a constant stream of data to continue refining the best approaches to avoid dangerous thrombosis events in people sick with the novel coronavirus.


2/23/21


https://labblog.uofmhealth.org/rounds/h ... lood-clots


It seems like every week new data comes out about blood clots in patients with COVID-19. Thrombosis puts someone hospitalized for COVID-19 more at risk for more problems like stroke or organ failure, while their body’s already dealing with inflammation from fighting the virus.

“The risk of thrombosis is real, it’s important and it’s something we need to be concerned about,” says vascular cardiologist Geoffrey Barnes, M.D., M.Sc., who sees patients at the Michigan Medicine Frankel Cardiovascular Center. He served as lead author on the Anticoagulation Forum Guidance Document.

The challenge, Barnes says, is whether, or to what extent, to change treatment approaches based on constant streams of limited data. While he’d prefer to have robust prospective data on this particular issue, clinician-scientists like Barnes instead have to rely on standards for intensive care treatment and acute respiratory distress syndrome as they sift through the flood of observational data.

Prevalence reports on blood clots and COVID-19 continue to change


Barnes says initial reports out of China and then the Netherlands showed rates up to near half of patients with venous thromboembolism, but follow-up data from U.S. institutions showed much lower rates.


“The real number is probably somewhere in between,” he says. “The severity of disease is really driving who will develop thrombosis. We currently use a low-dose heparin infusion as an intermediate approach in the ICU based on data from the H1N1 pandemic.”

Andrea Obi, M.D., a vascular surgeon and assistant professor at Michigan Medicine, was lead author of a recent review that explains the observed relationship between inflammation and thrombosis in COVID-19, finding that there is a link between immune system induced inflammatory response and blood clotting in the small and large blood vessels.

Levels of D-dimer, a protein biomarker generally measured to rule out blood clots, are markedly elevated in the COVID-19 patients with severe illness, she adds. Whether these patients could benefit from receiving blood thinners to improve outcome of the disease as had been useful in other severe pandemic pneumonias remains an active area of investigation.

“We’re closely monitoring our patients with COVID-19 for blood clots in order to best determine if and when to flip the switch from preventive to therapeutic anticoagulation,” Obi says.

Latest data confirms role for anticoagulation in treatment of COVID-related blood clots

The National Institutes of Health recently released interim data and promoted two main takeaways: moderately sick people with COVID-19 infection did better when they took full-dose blood thinners, but the sickest patients already in intensive care for COVID-19-related illness don’t do well with the full dose.


" The severity of disease is really driving who will develop thrombosis."
- Geoffrey Barnes, M.D., M.Sc.

And on the other end of the spectrum, a recent publication out of Michigan Medicine reported that patients who had worse cases of COVID-19 that required ventilator support had an imbalance in their bleeding-clotting system that increased the risk of bleeding.

It’s an assessment that makes sense to Barnes, also an assistant professor of internal medicine.

“I can hypothesize why the high risk patients were harmed: they may have had more bleeding risk and a more inflammatory component of thrombosis with critical illness, but we need more data to learn about this,” Barnes says. “I continue to be hesitant about drastic clinical changes before more data from randomized clinical trials are peer-reviewed and published.”

More than 45 randomized controlled trials have been started to evaluate anticoagulation in COVID-19, he says, but in the meantime, today’s patients need the best care possible.

Preventing clots in patients hospitalized for COVID-19

“While I’ve been a proponent of standard or mildly increased venous thromboembolism prophylaxis regimens for hospitalized patients with COVID-19 for nearly a year, I’m starting to re-assess that position,” Barnes says. “The early results from three clinical trials coordinated by the NIH have me considering which patients might benefit from full treatment doses of anticoagulation, even if they don’t have a confirmed VTE event.”

“Certainly, every hospitalized patient with COVID-19 needs to be receiving prophylaxis while we wait for the complete trial data to be released,” he adds. And it’s important to consider disparate outcomes in patients of color diagnosed with COVID-19 when making these individual treatment plans.

After patients leave the hospital, Barnes says data from London, Boston and New Orleans showed low rates of VTE. This is in contrast to initial numbers he’d reviewed that made him more concerned about this possibility.

“This tells me we do not need to be using universal prophylaxis after people leave the hospital,” he says. “We can be pretty selective.”

Patients managing COVID-19 infection at home


Most people infected with the virus don’t need to go to the hospital at all, though.

Data from Mass General Brigham Health System shows low rates of venous thromboembolism in non-hospitalized patients, Barnes explains, which jives with his treatment approach.

“I am not using VTE prophylaxis in my outpatients if they’re diagnosed with COVID-19. Rather, I’m only using it as an opportunity to reassess whether they should have been on blood thinners already, such as in the case of a patient who has a history of VTE,” Barnes says.
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Re: Covid 19 Blood Clotting issues

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Researchers reveal blood clot risk and anticoagulation benefits in discharged COVID-19 patients

4/9/21


https://www.news-medical.net/news/20210 ... ients.aspx


In the largest study of its kind, Feinstein Institutes for Medical Research and Northwell COVID-19 Research Consortium researchers reveal blood clot risk and anticoagulation benefits in hospitalized coronavirus disease 2019 (COVID-19) patients who have been recently discharged from the hospital. The report, recently published in the journal Blood, finds that prophylactic anticoagulants reduce the risk of major thromboembolic events and death by 46 percent.

The prospective multicenter registry, named CORE-19, examined 4,906 adult patients with COVID-19 who were hospitalized at Northwell Health hospitals, New York’s largest health system, between March 1 through May 31, 2020, and was led by Alex C. Spyropoulos, MD, professor at the Feinstein Institutes.

While blood clots have been observed in COVID-19 patients during hospitalization, there has been very little data to assess thrombotic risk and death, as well as predictors in the post-discharge period. The research looked to identify venous thromboembolism (VTE), such as deep vein thrombosis (DVT) and pulmonary embolism (PE), and arterial thromboembolism (ATE), such as stroke and myocardial infarction (MI), in patients released from the hospital within 90 days.

There are three main takeaways from the CORE-19 study. First, results showed that VTE, ATE, and all-cause mortality (ACM) occurred more than previously thought by clinicians, in 7.13 percent (350/4906 patients) of cases. Second, key risk factors for major thromboembolic events and death include advanced age, cardiovascular risk factors (like coronary artery disease, carotid occlusive disease, peripheral arterial disease), personal history of VTE, chronic kidney disease CKD, an intensive care unit stay, and an elevated VTE risk score (using the IMPROVE risk tool that has been developed by Dr. Spyropoulos’ team and is being used nationally). Third, post-discharge anticoagulants, mostly at prophylactic dosages, reduce the risk of major thromboembolic events and death by 46 percent.


"Since the start of the pandemic, we have seen that blood clots pose a fatal risk to patients while being hospitalized with COVID-19, but for those discharged, the prevalence and risk factors associated with thromboembolic events were unknown," said Dr. Spyropoulos, the study's principal investigator.

" This large dataset provides valuable insight and treatment options for recovering patients."

- Alex C. Spyropoulos, MD, Professor, Feinstein Institutes

The study showed the overall rate of 7.13 percent of post-discharge episodes, including:

Αll cause mortality rate of nearly 5 percent;
ATE rate of 1.71 percent (i.e. stroke, embolism);
VTE rate of 1.55 percent (i.e. mostly pulmonary embolism).

" This study reveals it is important to monitor COVID-19 survivors for dangerous blood clots even after they leave the hospital. By studying the enormous patient population treated at Northwell Health, Dr. Spyropoulos and his team have laid a solid foundation guiding future clinical trials.”

- Kevin J. Tracey, MD, President and CEO, Feinstein Institutes

Dr. Spyropoulos and Feinstein Institutes researchers have been leaders during the COVID-19 pandemic in efforts to prevent blood clots in patients. Since May 2020, the team enrolled hospitalized patients in a randomized controlled clinical trial named HEP-COVID, which aims to study the safety and efficacy of low-dose heparin as a blood clot prophylactic. Additionally, Dr. Spyropoulos is a member of the Executive Committee of the nationwide PREVENT-HD clinical trial looking to assess the benefits of anticoagulation in high-risk COVID-19 outpatients.

The Northwell Health Research Consortium began in early 2020 and has organized more than 500 clinicians, statisticians and scientists across the Feinstein Institutes and Northwell Health to conduct cutting-edge research about the COVID-19 pandemic. To date, more than 300 high-impact manuscripts have been written addressing the most pressing questions surrounding the virus.

The CORE-19 registry was funded in part by the Broxmeyer Fellowship in Clinical Thrombosis and Janssen Pharmaceuticals. Dimitri Giannis, MD, who is Dr. Spyropoulos’ fellow in Clinical Thrombosis, developed the database and is the first author on the Blood publication.

Source:

The Feinstein Institutes for Medical Research at Northwell Health
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Re: Covid 19 Blood Clotting issues

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Evidence that elevated blood glucose is a significant risk factor for severe COVID-19

5/3/21


https://www.news-medical.net/news/20210 ... ID-19.aspx


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus responsible for the outbreak of the COVID-19 disease. The virus emerged in China in late 2019, with viral transmission reaching pandemic proportions in early 2020. The average mortality rate of COVID-19 is under 2%, as this virus also causes asymptomatic infections in a large proportion of the population. However, in a small percentage of infected individuals, the virus causes symptomatic infections, leading to severe disease, hospitalizations, and deaths. There are also reports of persistent symptoms and long-term sequelae post recovery from COVID-19, which indicates a potentially more profound health crisis.

Containment strategies and lockdowns slow down the transmission of the virus and allow time to prepare a public health strategy, devise treatments, and develop vaccines without overwhelming the healthcare system. Although achieving herd immunity via mass vaccination will help eradicate the virus, there needs to be concerted coordination globally to significantly reduce transmission rates before the virus mutates into newer and more infectious variants that no longer respond to available vaccines.

This is a considerable challenge because the virus is currently infecting the global population at a high rate, providing ideal conditions for mutation. Hence there is a possibility that the disease may remain a health crisis for the foreseeable future. This makes it a priority to gain clear insights into the factors responsible for COVID-19 disease progression, which could help improve disease management and develop better treatment options.

The key symptoms of COVID-19 include cough, fever, and fatigue, with some people experiencing anosmia and a loss of taste. In people experiencing severe COVID-19, lung capacity decreases considerably and oxygen levels in the blood drop dangerously low, requiring supply of nasal oxygen and intubation using ventilators in very severe cases. The reasons behind the spectrum of differences in disease severity across the population and why COVID-19 affects the elderly population and those with comorbidities more severely are unclear.

Machine learning models to help mine scientific papers in the CORD-19 database

Researchers from Switzerland recently developed machine learning models to help mine 240,000 scientific papers in the CORD-19 database. Using the models, they constructed knowledge graphs to analyze the extracted data and search for a potential reason for disease severity. The study is published on the preprint server, medRxiv*.

The literature analysis pointed to elevated blood glucose levels as a leading facilitator in the progression of COVID-19. Evidence linking elevated glucose to various steps in the life cycle of the virus and presentation of COVID-19 symptoms were also found.

The observations suggested that blood glucose elevation provided ideal conditions for SARS-CoV-2 to attack the lung’s immune defense system and gain access to alveolar cells before binding to the human ACE2 receptor. High glucose levels also enabled the entry of the virus to the pulmonary cells and rapid viral replication within cells and induced a pulmonary inflammatory response. This massive immune response overwhelms an already weakened immune system and triggers a series of events causing systemic inflammation, cell damage, and the release of cytokines.

The researchers analyzed data across the papers, reconstructed the virus at the pulmonary airway surface, and then performed quantitative computational modeling of the impact of glucose levels on the infection process. They concluded that glucose level elevation could facilitate COVID-19 progression through multiple mechanisms. This explains the variation in disease severity across the population.

Summary of the findings


To summarize, the findings suggest that patients with severe COVID-19 usually present with elevated blood glucose levels, which impact several biochemical pathways that facilitate various steps in SARS-CoV-2 infection. Elevated blood glucose increases the amount of glucose in the pulmonary airway surface liquid (ASL), which destroys the primary antiviral defenses of the lungs and enables viral infection and replication.

Elevated glucose levels cause dysregulation of the immune response resulting in a cytokine storm and acute respiratory distress syndrome. Elevated glucose levels also work synergistically with the virus-dependent inactivation of ACE2 to rapidly escalate the disease to thrombotic events and multi-organ failure.

“The study proposes diagnostic recommendations, new areas of research and potential treatments, and cautions on treatment strategies and critical care conditions that induce elevations in blood glucose levels.”

*Important Notice


medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

Elevated Blood Glucose Levels as a Primary Risk Factor for the Severity of COVID-19, Emmanuelle Logette, Charlotte Lorin, Cyrille Favreau, Eugenia Oshurko, Jay S. Coggan, Francesco Casalegno, Mohameth François Sy, Caitlin Monney, Marine Bertschy, Emilie Delattre, Pierre-Alexandre Fonta, Jan Krepl, Stanislav Schmidt, Daniel Keller, Samuel Kerrien, Enrico Scantamburlo, Anna-Kristin Kaufmann, Henry Markram, medRxiv, 2021.04.29.21256294; doi: https://doi.org/10.1101/2021.04.29.21256294, https://www.medrxiv.org/content/10.1101 ... 21256294v1
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Re: Covid 19 Blood Clotting issues

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Emergency physicians use heparin alternative to treat vaccine-induced blood clot

5/5/21


https://www.news-medical.net/news/20210 ... -clot.aspx


A new case report, detailed in Annals of Emergency Medicine, is the first known case of a patient with VITT (vaccine-induced thrombotic thrombocytopenia) treated with a heparin alternative following the Centers for Disease Control and Prevention (CDC) guidance.

An otherwise healthy female patient in her 40s came to the emergency department at UCHealth University of Colorado Hospital twelve days after receiving the Johnson & Johnson vaccine with a headache, dizziness, and vision changes.

The patient was treated on April 13, 2021, the same day that the Centers for Disease Control and Prevention (CDC) announced a pause in the administration of the Johnson & Johnson vaccine. CDC guidance recommended treatment with heparin alternatives but did not recommended any specific alternative in that announcement.

Bivalirudin was given to the patient and the authors write that, "this patient's early outcomes suggest that bivalirudin may be a safe alternative to heparin in patients demonstrating a presentation consistent with VITT."'

" Our experience shows us that these clot reactions are very rare, but they can be treated. Americans can feel comfortable getting vaccinated and should discuss any vaccination concerns with their doctor. Getting vaccinated is a critical step in combatting this pandemic so we can return to our normal lives."

- R. Todd Clark, MD, MBA, Study Lead Co-Author and Assistant Professor, Emergency Medicine, University of Colorado School of Medicine

While more research is needed on the efficacy of this medicine, the early outcomes of this case may inform the decision making of other health professionals who may be selecting heparin alternatives for patients with VITT, the authors said.

Source:


American College of Emergency Physicians

Journal reference:


Clark, R. T., et al. (2021) Early Outcomes of Bivalirudin Therapy for Thrombotic Thrombocytopenia and Cerebral Venous Sinus Thrombosis after Ad26.COV2.S Vaccination: A Case Report. Annals of Emergency Medicine.
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Blood Clots and Other Hematological Issues In Covid Patients | Webinar | Yashoda Hospitals

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Blood Clots and Other Hematological Issues In Covid Patients | Webinar | Yashoda Hospitals


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Re: Covid 19 Blood Clotting issues

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Novel insights can open doors to combating clotting-related problems in COVID-19

6/4/21


https://www.news-medical.net/news/20210 ... ID-19.aspx


Driven by the mystery of the blood clots reported in both living and deceased COVID-19 patients, researchers from Shoolini University, India, dig deeper into the pathogenesis of COVID-19 and other similar viral diseases, looking for ways in which these clots could be formed. They propose a robust hypothesis, taking our understanding of clotting-related problems in COVID-19 one step further and opening doors to potential targeted therapies.

Soon after its emergence in December 2019, COVID-19, caused by the novel coronavirus SARS-CoV-2, rapidly spread worldwide resulting in a global pandemic within weeks and halting lives. Thus, early on, as most activities in the world shut down, attempts to understand SARS-CoV2 and COVID-19 kicked off in full swing.

SARS-CoV-2 was initially thought to be a respiratory pathogen, causing flu-like symptoms such as dry cough, sore throat, fever, and weakness. But over time several non-respiratory symptoms cropped up as well. One symptom gaining increasing attention was the blood clotting reported both in living and deceased patients. In several cases, the blood clots blocked normal blood flow, leading to stroke, organ failure, and even death. Yet, the mechanism of formation of these clots remain shrouded in a certain mystery.

As part of the continued attempt to clarify the mechanism, a team of researchers from Shoolini University, India, dove into the pathogenesis of SARS-CoV-2. Speaking of what inspired them, assistant professor at the university and lead scientist in the team, Dr. Pradeep Kumar, says: “Statements in the vein of ‘mysterious blood clots have been observed in COVID-19 patients’ were being made in newspapers and medical case reports. The blood clots were reported as mysterious because their cause is unknown. This fueled our interest to dig deeper.” Their conclusions are published in Medical Hypotheses.

SARS-CoV-2 primarily enters through the nose and mouth and moves to the lung. It binds to the angiotensin converting enzyme 2 (ACE2) receptor on the cells of these organs and enters the cells. In the cells, it releases its RNA, which then initiates its replication process, leading to infection. Interestingly, the ACE2 receptor is also harbored by other cells in the body, such as the kidneys, heart, intestine, and endothelial cells (or cells lining blood vessels). COVID-19 has been known to affect these organs in some cases.

Based on this knowledge, the team from Shoolini formulated their hypothesis: Upon entering the body, the virus can enter our circulation system. There, it recognizes and interacts with the widely expressed ACE2 receptor on endothelial cells. As it enters the endothelial cells and begins its replication process, it causes infection, which triggers an immune response and therefore, inflammation. It also injures the blood vessel lining. To repair the blood vessel, clotting and coagulating pathways activate. However, in the presence of inflammation, these pathways can go awry, leading to the formation of clots within the blood vessels, which can block the vessels at that site or travel down to other organs, such as the heart or brain, to cause fatal strokes and heart attacks.

Meanwhile, when the virus binds to the ACE2 receptor on the endothelial cells, the receptor is deactivated. Since the receptor normally protects endothelial cell function, its unavailability can help with the injuries and lead to an imbalance in the recruitment of platelets and clotting factors. This can enhance coagulation and clotting.

This hypothesis is based on a robust literature review of cases reporting similar mechanisms in relation to other influenza-like and respiratory viruses, and papers reporting post-mortem observations on COVID-19 patients. So, although it remains to be verified, it is an important step in unraveling the mystery of blood clotting in COVID-19.

Explaining the long-term implications of their study, Dr. Kumar says: “Our work will help us to understand in depth the diverse manifestations and pathophysiologies of COVID-19, which can eventually direct us towards developing targeted therapies to treat it and allied viral diseases.”

Indeed, such analyses bring hope in these dark times.

Source:

Shoolini University

Journal reference:


Biswas, S., et al. (2021) Blood clots in COVID-19 patients: Simplifying the curious mystery. Medical Hypotheses. doi.org/10.1016/j.mehy.2020.110371.
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Re: Covid 19 Blood Clotting issues

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Blood clot-busting nanocapsules could reduce existing treatment's side effects

6/2/21


https://phys.org/news/2021-06-blood-clo ... -side.html


Tested on human blood in the lab, the selective nanocapsules could reduce the side effects of a major blood clot dissolving drug, which include bleeding on the brain. If confirmed with animal tests, the nanocapsules could also make the drug more effective at lower doses.

Blood clots, also known as thrombi, are a key cause of strokes and heart attacks which are leading causes of death and ill-health worldwide. They can be treated with a clot dissolving drug called tissue plasminogen activator (tPA) which disrupts clots to clear the blocked blood vessel and re-establish blood flow.

However, tPA can cause life-threatening off-target bleeding, and lasts only a few minutes in circulation, so often requires repeated doses, which further increases the risk of bleeding. Consequently, it is only used for a minority of potentially eligible patients.

Now, researchers at Imperial College London have found that by encasing tPA in newly designed tiny capsules, it can be targeted more specifically to harmful blood clots with an increased circulation time. They designed the nanocapsules to attach to activated platelets present in thrombi, release the tPA payload and dissolve clots.

Lead author Dr. Rongjun Chen of Imperial's Department of Chemical Engineering said: "tPA has a narrow window between desired effect and side effects, so we have wrapped it in a package that extends this therapeutic window and minimizes the required dose. Our results are exciting but animal and clinical studies are required for validation."

Blood clots are made of blood cells called platelets which link together when activated. These platelets are held together with proteins called fibrinogen which bind to activated platelets and form 'bridges' between them. The new nanocapsule, called tPA-cRGD-PEG-NV, mimics fibrinogen so that it seeks out clots within blood vessels.

The researchers tested this on healthy human blood under both static conditions, where still blood was tested in petri dishes, and physiological flow conditions in a simulated blood vessel. To test flow conditions, they designed a computer model to simulate how the encapsulated tPA might act in circulating blood.

They found that the nanocapsules were highly selective in binding to activated platelets and that the time it took to dissolve clots was similar to that with unencapsulated tPA.

Co-corresponding author Professor Xiao Yun Xu of Imperial's Department of Chemical Engineering said: "We combined experimental and computational work to characterize this nanocapsule. To build our computer model we needed a mechanistic understanding of the interplay between the physical and biochemical processes of blood clot dissolving. The model could be very useful in animal and clinical trials of this potential nanomedicine, as well as in predicting optimal dosing for patients."

The purpose-built computer model was able to simulate nanocapsule transport to the clot site, its release of tPA, and its dissolution of clots. Professor Xu added: "Our simulation illustrated the potential in predicting the outcome of blood clot treatments in clinically relevant scenarios."

Co-author Professor Simon Thom of Imperial's National Heart and Lung Institute said: "We've found a way to make a clot-busting drug more precisely targeted, potentially enhancing efficacy and reducing catastrophic side effects. This promising work demonstrates the activity of nano-encapsulated tPA in a laboratory setting and paves the way for safer delivery of drugs with otherwise harmful side effects. Research is now needed in whole organisms to determine the capsule's effectiveness in a more realistic setting."

Next the researchers will test the encapsulated tPA in animals to see how it performs in whole organisms, especially for increasing circulation time and checking the computer model's ability to predict clot busting in a realistic setting. Dr. Chen added: "Once fully validated, the selective nanocapsules and the computer model could serve as powerful platforms for developing clot-busting nanomedicines."

More information: "Fibrinogen-mimicking, multiarm nanovesicles for human thrombus-specific delivery of tissue plasminogen activator and targeted thrombolytic therapy" Science Advances (2021). advances.sciencemag.org/lookup … 1126/sciadv.eabf9033
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