Covid 19 Blood Clotting issues

trader32176
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Re: Covid 19 Blood Clotting issues

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Thanks Tim ,
I guess I better add some more info here , so I can continue into studying other diseases that are affected with Covid blood clotting .


COVID-19 Leads to Hyperactivity in Platelets, Can Cause Clotting
2020-07-07 13:32:00
by Sara Karlovitch

https://www.pharmacytimes.com/news/covi ... e-clotting

Coronavirus disease 2019 (COVID-19) can make blood clotting cells “hyperactive,” which can cause potentially deadly clots, according to new research by University of Utah Health.

Researchers found that COVID-19 produced inflammatory proteins, which can alter the function of platelets and makes the patient more prone to developing dangerous blood clots. In certain patients, this can lead to cardiovascular failure, according to the study. The risk is higher for patients with underlying medical problems such as high blood pressure, obesity, and diabetes.

Researchers compared the blood of 41 patients with COVID-19 to blood samples from healthy individuals matched for age and sex. The patients were hospitalized at University of Utah Hospital in Salt Lake City. Of the 41 patients, 17 were in the ICU, 9 of whom were on ventilators. According to the press release, COVID-19 platelets aggregated more readily, which alters how platelets interact with the immune system. Most surprisingly, the researchers found that COVID-19 was not detected in the vast majority of platelets. This can mean the genetic changes within these cells are indirect.

According to the press release, one possible mechanism is inflammation. COVID-19 can affect the megakaryocytes, which are the cells that produce platelets. In test tube studies, researchers found that pre-treating infected platelets with aspirin prevented hyperactivity; however, further study is still needed. According to the press release, individuals should not treat COVID-19 with aspirin unless recommended by a physician.

"We found that inflammation and systemic changes, due to the infection, are influencing how platelets function, leading them to aggregate faster, which could explain why we are seeing increased numbers of blood clots in COVID patients,” senior author of the study and an assistant professor in the Department of Internal Medicine, Robert A. Campbell, PhD, said in the press release.

The researchers said they are exploring other treatment options. If they can determine how COVID-19 is interacting with megakaryocytes, they may be able to block that interaction and subsequently reduce the risk of blood clotting.

Reference:

COVID-19 causes 'hyperactivity' in blood-clotting cells (News Release); Salt Lake City, UT; June 30, 2020; EurekAlert!; accessed July 1, 2020.
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Re: Covid 19 Blood Clotting issues

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Post-mortem study of dead COVID-19 patients finds lung damage and blood clots

8/20/20


https://www.news-medical.net/news/20200 ... clots.aspx

A new post-mortem study of patients who have died from COVID-19 found severe damage to the lungs and signs of blood clotting in major organs.

Ten post-mortem examinations performed on patients with confirmed COVID-19 found that all patients had lung injuries and early scarring of the lungs as a result of the virus, as well as injury to their kidneys.
Nine patients also had thrombosis - a blood clot- in at least one major organ (heart, lung or kidney). The team were unable to investigate thrombosis in the tenth patient.

The research team behind the study believe that the findings could help guide clinicians on treating complications as a result of COVID-19, such as using blood thinners to prevent blood clots from developing. They also hope that better understanding of the key complications in severe cases could help clinicians develop new ways to monitor and treat the disease.

The study, published in The Lancet Microbe, was led by researchers at Imperial College London and Imperial College Healthcare NHS Trust. Although the numbers of patients examined is small, this is the largest study to date of post-mortem examinations on COVID-19 patients in England.

Dr Michael Osborn, Honorary Clinical Senior Lecturer at Imperial College London, Consultant Pathologist at Imperial College Healthcare NHS Trust and co-author of the study, said: "COVID-19 is a new disease and we have only had limited opportunities to comprehensively analyse tissues from patients at autopsy, to better understand what caused a patient's illness and death for research purposes. Our study is the first of its kind in the country to support existing theories from researchers and doctors on the wards that lung injuries, thrombosis and immune cell depletion are the most prominent features in severe cases of COVID-19. In the patients we looked at, we also saw evidence of kidney injuries and in some cases pancreatitis and these with our other findings will help clinicians develop new strategies to manage patients. ??"Autopsy based analysis of COVID-19 for research is vital to learn more of this disease as the pandemic develops. We are extremely grateful to those who consented to this research and appreciate the advancement of medical science their generosity will bring.

As a result of our work, we have worked with colleagues at the Royal College of Pathologists to produce national guidelines for autopsies in COVID-19 patients and in anticipation of a possible second wave of cases we have put systems in place to rapidly facilitate further studies in the future and so further our understanding on the nature and cause of the disease, which we hope would lead to more effective treatments and fewer deaths."


The UK has sadly had a large number of deaths related to COVID-19. The search for effective treatments will rely on an understanding of how the disease affects the body. The post-mortem examination is vital in this respect. The findings in this study support research from other autopsy groups worldwide and in the UK that describe the structural damage to organs caused by COVID-19. It also documents several unexpected complications. This increased understanding of COVID-19 can help clinical teams with the management of severe cases and also to monitor and treat further complications as a result of the disease."

-Dr Brian Hanley, Department of Cellular Pathology at Imperial College Healthcare NHS Trust and co-author of the study

During the lockdown period researchers nationally had very limited opportunities to carry out post mortem examinations for research purposes on patients who died from the disease. The team wanted to see whether they can glean new insights on how the virus infects the cells of the body by studying tissue samples from patients who died as a result of severe COVID-19.

The team performed full post-mortem examinations and biopsies on ten patients aged 22-97 at Imperial College Healthcare NHS Trust hospitals during March-June. Full consent for post mortem with widespread tissue sampling and use of the tissue for research was sought from the relatives and friends of the deceased in line with national protocols. Seven of the patients were men and four were women. Six of the patients were from a BAME background and four patients were white.

In the patients studied, high blood pressure and chronic obstructive pulmonary disease - the name for a group of lung conditions that cause breathing difficulties - were the most common contributing factors to death. All patients developed a fever and had at least two respiratory symptoms such as cough and shortness of breath during the early stages of the disease. Most patients died within three weeks of presenting with symptoms and treatments varied across the cohort.

The study team also reported six main findings:

All patients had diffuse alveolar damage (DAD). DAD is a term used to describe a pattern of lung injury which can be seen as a result of viral infection. This type of lung injury can affect both gas exchange (oxygen and carbon dioxide) and blood flood in the lungs.
All patients fully assessed Nine of the ten patients had some form of thrombosis- blood clot - in at least one major organ (it was not possible to investigate thrombosis in the tenth patient). Thrombosis prevents blood from flowing normally through the circulatory system and can lead to strokes and heart attacks. The researchers found thrombi in the lungs of eight patients, the heart of five patients and the kidneys of four patients. They believe that this supports the theory that COVID-19 causes circulatory complications and that patient treatment could be augmented with blood thinning medication to prevent blood clots
All patients had evidence of acute renal tubular injury - a kidney injury that can lead to kidney failure or damage. The main causes are low blood flow to the kidneys and severe infections. It often affects patients who are in hospital and intensive care units.

T-Lymphocyte Depletion (TLD) in the spleen and the lymph nodes was another consistent finding. T-lymphocytes (white blood cells) are a major component of the immune system and play a role in destroying infections. TLD is a reduction in T-lymphocytes, which alters the immune system and its response. Haemophagocytosis is another consistent finding in this group, which occurs when the immune system overreacts to an infection and destroys some of its own cells
The researchers found evidence of acute pancreatitis in two of the patients. Acute pancreatitis is a condition where the pancreas becomes inflamed. It can be treated with fluids into the veins but in some cases can develop into serious complications and cause organ failure. Damage to the pancreas in COVID-19 patients has not been reported before but it is not clear in this study whether the pancreatitis was related to COVID-19 infection or other causes
The researchers also found evidence of a rare fungal infection, in one of the patients, called Mucormycosis. Mucormycosis is an infection that may spread through the bloodstream to affect another part of the body. Severe infections can involve the lungs, brain and other organs including the kidneys, spleen and heart.

The team is working with a range of research groups both nationally and internationally to perform more detailed analyses of these tissues and is hoping that this research will expand to include a wider range of patients.
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TimGDixon
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Re: Covid 19 Blood Clotting issues

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Thats an important study even if its only ten.
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Re: Covid 19 Blood Clotting issues

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Anticoagulation therapy associated with improved survival among COVID-19 patients

8/27/20

https://www.news-medical.net/news/20200 ... ients.aspx

Early in the COVID-19 pandemic, Mount Sinai researchers were among the first to show that anticoagulation therapy was associated with improved survival among hospitalized COVID-19 patients. But many questions remained-;about the size of the potential benefit, and about what dosage of this therapy might be more effective.

Now, the research team has suggested some possible answers, in a paper published in the August 26 online issue of the Journal of the American College of Cardiology.

In this observational study, the researchers found all regimens of anticoagulants-;drugs that prevent blood clotting-;were far superior to no anticoagulants in COVID-19 patients.

More specifically, patients on both a "therapeutic" or full dose, and those on a "prophylactic" or lower dose, showed about a 50 percent higher chance of survival, and roughly a 30 percent lower chance of intubation, than those not on anticoagulants.

The researchers looked at six different anticoagulant regimens, including both oral and intravenous dosing, within both therapeutic and prophylactic groups. They observed that therapeutic and prophylactic subcutaneous low-molecular weight heparin, and therapeutic oral apixaban may lead to better results.

This work from the Mount Sinai COVID Informatics Center provides additional insight on the role of anticoagulation in the management of patients admitted to the hospital with COVID-19. Although this is an observational study, it helped in the design of a large-scale international clinical trial that we are coordinating. The randomized trial focuses on those three antithrombotic regimens-; therapeutic and prophylactic subcutaneous low-molecular weight heparin, and therapeutic oral apixaban."

-Valentin Fuster, MD, PhD, Senior Corresponding Author and Director, The Mount Sinai Hospital

Fuster is also Physician-in-Chief of The Mount Sinai Hospital.

This study is an extension of Mount Sinai research that showed that treatment with anticoagulants was associated with improved outcomes both in and out of the intensive care unit among hospitalized COVID-19 patients. The work was prompted by the discovery that many patients hospitalized with COVID-19 developed high levels of life-threatening blood clots.

The team of investigators evaluated electronic medical records of 4,389 confirmed COVID-19-positive patients admitted to five hospitals in the Mount Sinai Health System in New York City (The Mount Sinai Hospital, Mount Sinai West, Mount Sinai Morningside, Mount Sinai Queens, and Mount Sinai Brooklyn) between March 1 and April 30, 2020.

They specifically looked at survival and death rates for patients placed on therapeutic and prophylactic doses of blood thinners (oral antithrombotics, subcutaneous heparin, and intravenous heparin) versus those not placed on blood thinners.

The researchers used a hazard score to estimate risk of death, which took relevant risk factors into account before evaluating the effectiveness of anticoagulation, including age, ethnicity, pre-existing conditions, and whether the patient was already on blood thinners.

The researchers also took into account and corrected for disease severity, including low oxygen saturation levels and intubation.

Of the patients analyzed, 900 (20.5 percent) received a full-treatment dose of anticoagulants. Another 1,959 patients (44.6 percent) received a lower, prophylactic dose of anticoagulants, and 1,530 (34.5 percent) were not given blood thinners.

There was a strong association between blood thinners and reduced likelihood of in-hospital deaths: both therapeutic and prophylactic doses of anticoagulants reduced mortality by roughly 50 percent compared to patients on no blood thinners.

Overall, 467 (10.6 percent) of the patients required intubation and mechanical ventilation during their hospitalization. Those on therapeutic blood thinners had 31 percent fewer intubations than those not on blood thinners, while those on prophylactic blood thinners had 28 percent fewer.

Bleeding rates-;a known complication of blood thinners-;were surprisingly low overall among all patients (three percent or less), but slightly higher in the therapeutic group compared to the prophylactic and no-blood-thinner groups, the researchers said. Their findings suggest that clinicians should evaluate patients on an individual basis given the benefit-risk tradeoff.

Separately, the researchers looked at autopsy results of 26 COVID-19 patients and found that 11 of them (42 percent) had blood clots-;pulmonary, brain, and/or heart-;that were never suspected in the clinical setting. These findings suggest that treating patients with anticoagulants may be associated with improved survival.

"This report is much more in-depth than our previous brief report and includes many more patients, longer follow-up, and rigorous methodology. Clearly, anticoagulation is associated with improved outcomes and bleeding rates appear to be low," says corresponding author Anu Lala, MD, Assistant Professor of Medicine (Cardiology) and Director of Heart Failure Research at the Icahn School of Medicine at Mount Sinai.

"As a clinician who has treated COVID-19 patients on the front lines, I recognize the importance of having answers as to what the best treatment for these patients entails, and these results will inform the design of clinical trials to ultimately give concrete information."

"These observational analyses were done with the highest level of statistical rigor and provide exciting insights into the association of anticoagulation with critical in-hospital outcomes of mortality and intubation," says first author Girish Nadkarni, MD, Co-Founder and Co-Director of the Mount Sinai COVID Informatics Center and Clinical Director of the Hasso Plattner Institute for Digital Health at Mount Sinai.

"We are excited that results from this observational study in one of the largest and most diverse hospitalized populations have led to an ongoing trial of type, duration, and doses of anticoagulation. Ultimately we hope this work will lead to improved outcomes and treatment for COVID-19 patients."

"This work highlights the need to better understand the disease from a diagnostic and therapeutic point of view and the importance of conducting properly designed diagnostic and interventional studies," explains co-author Zahi Fayad, PhD, Co-Founder of the Mount Sinai COVID Informatics Center and Director of Mount Sinai's BioMedical Engineering and Imaging Institute.
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Re: Covid 19 Blood Clotting issues

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High levels of blood clotting factor V in severe COVID‐19 associated with worse outcomes

9/8/20

https://www.news-medical.net/news/20200 ... comes.aspx

Patients hospitalized with severe COVID-19 infections who have high levels of the blood clotting protein factor V are at elevated risk for serious injury from blood clots such as deep vein thrombosis or pulmonary embolism, investigators at Massachusetts General Hospital (MGH) have found.

On the other hand, critically ill patients with COVID-19 and low levels of factor V appear to be at increased risk for death from a coagulopathy that resembles disseminated intravascular coagulation (DIC), a devastating, often fatal abnormality in which blood clots form in small vessels throughout the body, leading to exhaustion of clotting factors and proteins that control coagulation, report Elizabeth M. Van Cott, MD, investigator in the deparment of pathology at MGH and colleagues.

Their findings, based on studies of patients with COVID-19 in MGH intensive care units (ICUs), point to disturbances in factor V activity as both a potential cause of blood clotting disorders with COVID-19, and to potential methods for identifying at-risk patients with the goal of selecting the proper anticoagulation therapy.

The study results are published online in the American Journal of Hematology.

"Aside from COVID-19, I've never seen anything else cause markedly elevated factor V, and I've been doing this for 25 years," Van Cott says.

Patients with severe COVID-19 disease caused by the SARS-CoV-2 virus can develop blood clots in medical lines (intravenous lines, catheters, etc), and in arteries, lungs, and extremities, including the toes. Yet the mechanisms underlying coagulation disorders in patients with COVID-19 are still unknown.

In March 2020, in the early days of the COVID-19 pandemic in Massachusetts, Van Cott and colleagues found that a blood sample from a patient with severe COVID-19 on a ventilator contained factor V levels high above the normal reference range. Four days later, this patient developed a saddle pulmonary embolism, a potentially fatal blood clot occurring at the junction of the left and right pulmonary arteries.

This pointed the investigators to activity of factor V as well as factor VIII and factor X, two other major clotting factors. They studied the levels of these clotting factors and other parameters in a group of 102 consecutive patients with COVID-19, and compared the results with those of current critically ill patients without COVID-19, and with historical controls.

They found that factor V levels were significantly elevated among patients with COVID-19 compared with controls, and that the association between high factor V activity and COVID-19 was the strongest among all clinical parameters studied.

In all, 33 percent of patients with factor V activity well above the reference range had either deep vein thrombosis or a pulmonary embolism, compared with only 13 percent of patients with lower levels. Death rates were significantly higher for patients with lower levels of factor V (30 percent vs. 12 percent), with evidence that this was due to a clinical decline toward a DIC-like state.

Van Cott and colleagues also found that the clinical decline toward DIC was foreshadowed by a measurable change in the shape or "waveform" of a plot charting light absorbance against the time it takes blood to coagulate (waveform of the activated partial thromboplastin time, or aPTT).

"The waveform can actually be a useful tool to help assess patients as to whether their clinical course is declining toward DIC or not," Van Cott explains. "The lab tests that usually diagnose DIC were not helpful in these cases."

Importantly, the MGH investigators note that factor V elevation in COVID-19 could cause misdiagnosis of some patients, because under normal circumstances factor V levels are low in the presence of liver dysfunction or DIC. Physicians might therefore mistakenly assume that patients instead have a deficiency in vitamin K.

"This investigation was spurred by the surprising case we encountered, and was conducted rapidly by an interdisciplinary pathology team at MGH during the peak of the pandemic," said Jonathan Stefely, MD, PhD, one of the study's co-authors.
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Re: Covid 19 Blood Clotting issues

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COVID-19 and Blood Clots

September 9, 2020

https://hms.harvard.edu/news/covid-19-blood-clots

Patients hospitalized with severe COVID-19 infections who have high levels of the blood clotting protein factor V are at elevated risk for serious injury from blood clots such as deep vein thrombosis or pulmonary embolism, according to a new study by Harvard Medical School investigators at Massachusetts General Hospital.

On the other hand, critically ill patients with COVID-19 and low levels of factor V appear to be at increased risk for death from a form of coagulopathy that resembles disseminated intravascular coagulation (DIC)—a devastating, often fatal abnormality in which blood clots form in small vessels throughout the body, leading to exhaustion of clotting factors and proteins that control coagulation.

Their findings, based on studies of patients with COVID-19 in Mass General intensive care units, point to disturbances in factor V activity as both a potential cause of blood clotting disorders with COVID-19 and potential methods for identifying at-risk patients with the goal of selecting the proper anticoagulation therapy.

The study results are published online Aug. 24 in the American Journal of Hematology.

“Aside from COVID-19, I’ve never seen anything else cause markedly elevated factor V, and I’ve been doing this for 25 years,” said senior study author Elizabeth Van Cott, HMS professor of pathology at Mass General.

Patients with severe COVID-19 caused by the SARS-CoV-2 virus can develop blood clots in medical lines, such as intravenous lines and catheters, and in arteries, lungs and extremities, including the toes. Yet the mechanisms underlying coagulation disorders in patients with COVID-19 are still unknown.

Surprising case

In March 2020, in the early days of the COVID-19 pandemic in Massachusetts, Van Cott and colleagues found that a blood sample from a patient with severe COVID-19 on a ventilator contained factor V levels high above the normal reference range. Four days later, this patient developed a saddle pulmonary embolism, a potentially fatal blood clot occurring at the junction of the left and right pulmonary arteries.

This pointed the investigators to activity of factor V as well as factor VIII and factor X, two other major blood clotting protein factors. They studied the levels of these clotting factors and other parameters in a group of 102 consecutive patients with COVID-19 and compared the results with those of current critically ill patients without COVID-19, as well as against historical controls.

The researchers found that factor V levels were significantly elevated among patients with COVID-19 compared with controls, and they found the association between high factor V activity and COVID-19 was the strongest among all clinical parameters studied.

In all, 33 percent of patients with factor V activity well above the reference range had either deep vein thrombosis or a pulmonary embolism, compared with only 13 percent of patients with lower levels. Death rates were significantly higher for patients with lower levels of factor V, with evidence suggesting that this was due to a clinical decline toward a DIC-like state.

Van Cott and colleagues also found that the clinical decline toward DIC was foreshadowed by a measurable change in the shape, or waveform, of a plot charting light absorbance against the time it takes blood to coagulate.

“The waveform can actually be a useful tool to help assess patients as to whether their clinical course is declining toward DIC or not,” Van Cott said. “The lab tests that usually diagnose DIC were not helpful in these cases.”

Importantly, the investigators note that factor V elevation in COVID-19 could cause misdiagnosis of some patients, because under normal circumstances factor V levels are low in the presence of liver dysfunction or DIC. Physicians might therefore mistakenly assume that patients instead have a deficiency in vitamin K.

“This investigation was spurred by the surprising case we encountered and was conducted rapidly by an interdisciplinary pathology team at Mass General during the peak of the pandemic,” said study co-author Jonathan Stefely, HMS clinical fellow in pathology at Mass General.

The study was internally funded by Mass General.
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Re: Covid 19 Blood Clotting issues

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NIH ACTIV initiative launches adaptive clinical trials of blood-clotting treatments for COVID-19

9/10/20


https://www.nih.gov/news-events/news-re ... s-covid-19

The National Institutes of Health has launched two of three adaptive Phase 3 clinical trials evaluating the safety and effectiveness of varying types of blood thinners to treat adults diagnosed with COVID-19. Part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative, these trials will be conducted at more than 100 sites around the world and will involve patients in various clinical settings — those who have not been hospitalized, those currently hospitalized and those discharged after hospitalization for moderate to severe disease.

Collectively known as ACTIV-4 Antithrombotics, the trials will provide critical insights that could help guide the care of patients with COVID-19, particularly those who suffer from life-threatening blood clots. The trial for hospitalized COVID-19 patients and the trial for patients with COVID-19 who have not been hospitalized are now underway. A third trial to start later will focus on patients discharged after hospitalization for moderate to severe COVID-19 disease. All three clinical trials will be coordinated and overseen by the National Heart, Lung, and Blood Institute (NHLBI), part of NIH, and funded through Operation Warp Speed(link is external).

Researchers have noted that many patients who have died from COVID-19 — the deadly disease caused by SARS-CoV-2 — had formed blood clots throughout their bodies, including in their smallest blood vessels. This unusual clotting, one of many life-threatening effects of the disease, has caused multiple health complications, from organ damage to heart attack, stroke and pulmonary embolism.

ACTIV-4 Antithrombotics will be recruiting at sites with significant COVID-19 burden and are interested in enrolling patients in studies testing potential treatments to prevent or reduce the formation of blood clots. The adaptive design of the protocol allows different blood thinners to be started, stopped or combined during the study in response to emerging trial data. This approach accelerates the timeline for testing different agents without compromising safety.

Antithrombotics, also known as blood thinners or anticoagulants, keep blood protein and platelets from turning into clumps or sticking to each other, but doctors have not yet figured out if, and at what point during the course of the disease, blood thinners might be effective at treating patients with COVID-19.

“There is currently no standard of care for anticoagulation in hospitalized COVID-19 patients, and there is a desperate need for clinical evidence to guide practice,” said NIH Director Francis S. Collins, M.D., Ph.D. “Conducting trials using multiple existing networks of research sites provides the scale and speed that will get us answers faster.”

ACTIV-4 Antithrombotics Inpatient will investigate the safety and effectiveness of using varying doses of the blood thinner heparin to prevent clotting events and improve outcomes in hospitalized COVID-19 patients. Patients will be assigned to either a low or high dose of heparin, and as the trial progresses, additional antithrombotics may be tested, depending on the trial results. All participants in the study will continue to receive clinical care as indicated for their condition.

ACTIV-4-Antithrombotics Outpatient will investigate whether anticoagulants or antithrombotic therapy can reduce life-threatening cardiovascular or pulmonary complications in newly diagnosed COVID-19 patients who do not require hospital admission. Researchers will also collect patient data and blood samples to help identify new drug targets and biomarkers that may help identify a patient’s risk of developing complications related to COVID-19. Participants will be assigned to take either a placebo, aspirin or a low or therapeutic dose of the blood thinner apixaban.

“We must use therapies that support the natural inhibitors of clotting in the blood,” said Keith Hoots, M.D., director of NHLBI’s Division of Blood Disorders and Resources. “Heparin has shown promise, but we really need clinical trial data to determine how much blood thinner, or even anti-platelet medication, to give.”

“By leveraging the infrastructure and expertise of our existing research networks, we can more rapidly gather the scientific evidence needed to help prevent or treat these very serious complications caused by COVID-19,” said NHLBI Director Gary H. Gibbons, M.D. “Harnessing and integrating the assets within existing networks gives us an enormous head start and will allow us to get answers much sooner.”

Trial planning and development work is being done through a collaborative effort with a number of universities, including the University of Pittsburgh; University of Michigan, Ann Arbor; New York University, New York City; Brigham and Women’s Hospital, Boston; University of Illinois at Chicago; University of North Carolina at Chapel Hill; and The University of Vermont, Burlington.

NIH announced the ACTIV public-private partnership in April 2020 to develop a coordinated national research response to speed COVID-19 treatment and vaccine options. As part of this partnership, Bristol-Myers Squibb/Pfizer have agreed to donate the treatments for the trials for patients with COVID-19 who have not been hospitalized. Managed by the Foundation for the National Institutes of Health, ACTIV brings together multiple partners from government, industry, academia and non-profit organizations. For more information about this and other ACTIV therapeutic trials, visit the ACTIV Therapeutics page.

About the National Heart, Lung, and Blood Institute (NHLBI): NHLBI is the global leader in conducting and supporting research in heart, lung, and blood diseases and sleep disorders that advances scientific knowledge, improves public health, and saves lives. For more information, visit https://www.nhlbi.nih.gov/.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
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Re: Covid 19 Blood Clotting issues

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Study provides in-depth analysis on VTE risk in COVID-19 patients

10/1/20


https://www.news-medical.net/news/20201 ... ients.aspx

In a systematic review of the worldwide published data on "Venous thromboembolism (VTE) in COVID-19 patients", Cihan Ay, Stephan Nopp, and Florian Moik from the Department of Medicine I, Clinical Division of Haematology and Haemostaseology, now for the first time, provide an in-depth analysis on the risk of VTE in patients hospitalized for COVID-19. While hospitalized patients at general wards have a VTE risk between 5 and 11%, the risk of developing deep vein thrombosis or pulmonary embolism in critically ill patients is 18 to 28%.

" From the beginning of the COVID-19 pandemic, studies reported an increased rate of thrombosis and pulmonary embolism in patients with COVID-19. On the basis of these reports, but without robust evidence from controlled interventional studies, global treatment strategies were developed, recommending more intense thromboprophylaxis strategies. Our study now offers a better understanding of the underlying risk and, therefore, aids in individual treatment decisions based on accurate risk assessment for the different patient groups."

-Cihan Ay, Principal Investigator, Medical University of Vienna

Within their review of the literature, the authors assessed a total of 5,951 studies published in the field of VTE in COVID-19. Of those, 86 studies were found eligible for inclusion and reported rates of thrombosis and pulmonary embolism in COVID-19 patients.

After excluding additional studies due to underlying risk of bias in a structured assessment, 66 studies (28,173 patients) were found eligible to perform a meta-analysis to provide a robust estimate on risk of VTE in COVID-19.

The main findings are as follows: the overall VTE risk in hospitalized patients with COVID-19 is 14%, despite rigorous thromboprophylaxis regimens in most studies. Further, high heterogeneity in VTE rates was found between different patient subgroups.

The rate was highest in patients admitted to intensive care units, with 23% of patients suffering VTE. Patients admitted to general wards suffered VTE in 8% of the cases. These findings underline the high risk of VTE in COVID-19 patients.

In addition, the authors specifically focused on estimating the risk of potentially life-threatening pulmonary embolism. The result: "This risk is considerably higher than in other comparable serious medical illnesses and ranges between 10 and 18% in COVID-19 patients requiring intensive care. Further, astonishingly, deep vein thrombosis was detected in almost half of the hospitalised COVID-19 patients who had been systematically screened for thrombosis using ultrasound."

These findings underscore the strong impact of COVID-19 on the blood-clotting system.
In addition, an exploratory analysis revealed that patients who developed deep vein thrombosis or pulmonary embolism during hospitalization had significantly higher D-dimer concentrations at admission, a laboratory parameter that indicates an activated coagulation system.

This finding might be used to help develop personalized, risk-stratified thromboprophylaxis strategies in the future.

In summary, the authors provide a detailed evaluation of the risk of VTE based on the severity of the disease. Future studies need to determine whether elevated D-dimer at hospital admission justifies intensification of anticoagulant treatment in hospitalized patients with COVID-19.
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Re: Covid 19 Blood Clotting issues

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Blood Clotting Tied to Worse COVID-19 Outcomes

9/16/20

https://www.webmd.com/lung/news/2020091 ... 9-outcomes

WEDNESDAY, Sept. 16, 2020 (HealthDay News) -- Most people now know that COVID-19 can cause blood clots, potentially leading to paralysis, stroke, heart attack and death.

While it's not clear precisely how SARS-CoV-2 causes clots, a new study suggests that the amount of a particular protein -- called factor V -- in a patient's blood may have something to do with it.

In March, researchers at Massachusetts General Hospital obtained a blood sample from a patient with severe COVID-19 and noticed something unusual. The patient's blood had significantly above-normal levels of factor V.

Researchers then studied more than 100 patients treated in the intensive care unit for COVID-19.

High levels of factor V were found across the group, and nearly half of the patients had above-normal levels. When researchers compared the samples to historical records, more than 1 in 10 patients had higher factor V levels than had been seen before at the hospital.

"Aside from COVID-19, I've never seen anything else cause markedly elevated factor V, and I've been doing this for 25 years," study co-author Dr. Elizabeth Van Cott said in a hospital news release. She is a pathology investigator at Mass General and a pathology professor at Harvard Medical School.

The study found that patients with elevated factor V were more likely to have blood clots in the lungs, called pulmonary embolism, and deep vein thrombosis (DVT), or clots in the veins.

Of patients with high levels of factor V, one-third had either DVT or a pulmonary embolism, compared with 13% of patients with lower levels.

While patients with high factor V levels were at greater risk for clotting problems, patients with lower factor V levels had a higher risk of death, researchers found.

A decrease in factor V levels might indicate patients are progressing to a serious and often fatal condition in which clotting processes become overactive, Van Cott and colleagues said.

They said the findings could help identify which patients are at increased risk of blood clots and death.

The findings were recently published online in the American Journal of Hematology.
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Re: Covid 19 Blood Clotting issues

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Pathways contributing to hypercoagulability in severe SARS‐CoV‐2 patients

10/11/20


https://www.news-medical.net/news/20201 ... ients.aspx

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a novel RNA virus from the betacoronavirus family. Members of the coronavirus family have adapted to human hosts and effectively get transmitted from person to person via the respiratory route. Seven different coronaviruses with varying incubation periods, transmissibility, and disease severity have affected humankind so far. They are, in the order of their mortality rate, MERS‐CoV > SARS‐CoV > SARS‐CoV‐2 > HKU1 ≃ NL63 ≃ OC43 ≃ 229E.

Of these, SARS‐CoV‐2 is unique and has a relatively long incubation time. Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 emerged in Wuhan, China, and has now progressed into a pandemic of unprecedented proportions, causing significant morbidity and mortality worldwide. Apart from its ability to cause acute respiratory failure, this virus is also capable of triggering disturbances in hemostatic balance, which is a significant problem in patients with moderate and severe disease. These disturbances can lead to hypercoagulability and disseminated intravascular coagulation (DIC), causing organ failure, heart and kidney complications, and stroke.

In recent weeks, blood clotting disorders have surfaced as one of the major complications in severe COVID-19 patients. Remarkably, over 70% of deaths associated with COVID-19 are attributed to clotting-related complications, including pulmonary embolism, multi-organ failure, and strokes, which have been confirmed by autopsy.

In a study by researchers from the University of South Carolina School of Medicine, The Pennsylvania State University, and Postgraduate Institute of Medical Education & Research, Chandigarh, India, explored the possible mechanisms of the clotting disorder, focusing on the role of hypoxia-related activation of coagulation factors; cytokine storm, activation of neutrophils, and the release of neutrophil extracellular traps. This study is published in the journal Reviews in Medical Virology.

In the study, the researchers briefly reviewed how multifactorial pathologies and molecular responses affect the coagulation system and the fibrinolytic system in COVID‐19 patients.

‘Cytokine storm’ leads to destructive inflammatory responses in severe COVID-19

A typical SARS‐CoV‐2 infection runs for about 20 days. The initial infection manifests a set of clinical symptoms ranging between sore throat, dry cough, fever, myalgias, and gastrointestinal symptoms such as nausea, anorexia, and diarrhea. Some infected patients also experience a temporary loss of smell and taste.

As the infection progresses to its second or third week, patients show signs of breathing difficulty, a range of hematological signs including lymphopenia and neutrophilia, and coagulation abnormalities such as pulmonary embolism, blood thickening, and rarely, some neurological symptoms.

Patients with severe COVID-19 can develop a condition known as a “cytokine storm,” in which cytokines, released by monocytes, lymphocytes, and alveolar macrophages that come in contact with the virus, give rise to destructive inflammatory responses.

Damage to the liver and a virus-induced increase in D‐dimers along with the cytokine storm alters the blood coagulation factors and causes DIC. Patients with fatal infection exhibit acute respiratory distress syndrome, myocardial injury, stroke, and multi-organ function damage during the final stages of infection.

Anti‐inflammatory therapeutics reduce the impact of cytokine storm and minimize severe disease

Amidst this unprecedented pandemic situation caused by a novel virus, the literature on the SARS‐CoV‐2 virus is evolving rapidly on a daily basis. Using the current understanding, the researchers proposed a mechanism that possibly drives coagulopathy in COVID‐19 patients.

According to their findings, the virus enters and binds to its receptor, and then attaches itself to the upper respiratory tract and lung tissues. The inflammation and hypoxic conditions caused by the infection lead to the release of TF, IL6, and other chemokines, which attract more lymphocytes and neutrophils into the lungs. Reactive immune molecules leak into the circulation and activate platelets and thrombin, triggering the clotting process. This results in the induction of a microthrombosis process, which causes PE, DIC, and multi-organ failure due to oxygen‐ and nutrient‐starvation.

The researchers believe that symptomatic treatment with anti‐inflammatory therapeutics and close monitoring of platelet counts and D‐dimer and fibrinogen levels might help mitigate the effects of cytokine storm and diagnose PE early in COVID‐19 patients. Also, using antiviral candidates such as remdesivir and hydroxychloroquine that target virus entry and replication could help speed up recovery times and bring down death rates. The team hopes that future studies will help improve understanding of various pathways contributing to thrombus formation in SARS‐CoV‐2-infected patients.

“Future observations and experimental studies will play a vital role in portraying a clear picture in understanding the physiological, molecular, and cellular signaling pathways that contribute to SARS‐CoV‐2–related thrombus formation.”

Source


Pujhari, S., Paul, S., Ahluwalia, J. and Rasgon, J.L. (2020), Clotting disorder in severe acute respiratory syndrome coronavirus 2. Rev Med Virol. doi:10.1002/rmv.2177, https://onlinelibrary.wiley.com/doi/10.1002/rmv.2177
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