Tag: blood clots

Categories : IT in Healthcare Medical Research & TechnologyTags :

New, Inexpensive Medical Computers that Run on Air

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Closeup of the pneumatic logic sensing device. (William Grover/UCR)

Medical engineers have developed a new, air-powered computer sets off alarms when certain medical devices fail. The invention is a more reliable and lower-cost way to help prevent blood clots and strokes – all without electronic sensors. 

Described in a paper in the journal Device, the computer not only runs on air, but also uses air to issue warnings. It immediately blows a whistle when it detects a problem with the lifesaving compression machine it is designed to monitor.

Intermittent pneumatic compression (IPC) devices are pneumatic leg sleeves that periodically squeeze a patient’s legs to increase blood flow. This prevents clots that lead to blocked blood vessels, strokes, or death. Typically, these machines are powered and monitored by electronics.

“IPC devices can save lives, but all the electronics in them make them expensive. So, we wanted to develop a pneumatic device that gets rid of some of the electronics, to make these devices cheaper and safer,” said William Grover, associate professor of bioengineering at UC Riverside and corresponding paper author.

Pneumatics move compressed air from place to place. Emergency brakes on freight trains operate this way, as do bicycle pumps, tire pressure gauges, respirators, and IPC devices. It made sense to Grover and his colleagues to use one pneumatic logic device to control another and make it safer.

This type of device operates in a similar way to electronic circuits, by making parity bit calculations. “Let’s say I want to send a message in ones and zeroes, like 1-0-1, three bits,” Grover said. “Decades ago, people realized they could send these three bits with one additional piece of information to make sure the recipient got the right message.” 

That extra piece of information is called a parity bit. The bit is a number – 1 if the message contains an odd number of ones, and 0 if the message contains an even number of ones. Should the number one appear at the end of a message with an even number of bits, then it is clear the message was flawed. Many electronic computers send messages this way. 

An air-powered computer uses differences in air pressure flowing through 21 tiny valves to count the number of ones and zeroes. If no error in counting has occurred, then the whistle doesn’t blow. 

If it does blow, that’s a sign the machine requires repairs. Grover and his students, in a video demonstrating the air computer, are shown damaging an IPC device with a knife, rendering it unusable. Seconds later, the whistle blows.

“This device is about the size of a box of matches. It replaces a handful of sensors as well as a computer,” Grover said. “So, we can reduce costs while still detecting problems in a device. And it could also be used in high humidity or high temperature environments that aren’t ideal for electronics.”

The IPC device monitoring is only one application for air computing. For his next project, Grover would like to design a device that could eliminate the need for a job that kills people every year: moving around grain at the top of tall silos. 

Tall buildings full of corn or wheat, grain silos are a common sight in the Midwest. Often times, a human has to go inside with a shovel to break up the grains and even out the piles inside. 

“A remarkable number of deaths occur because the grain shifts and the person gets trapped. A robot could do this job instead of a person. However, these silos are explosive, and a single electric spark could blow a silo apart, so an electronic robot may not be the best choice,” Grover said. “I want to make an air-powered robot that could work in this explosive environment, not generate any sparks, and take humans out of danger.” 

Air-powered computing is an idea that has been around for at least a century. People used to make air-powered pianos that could play music from punched rolls of paper. After the rise of modern computing, engineers lost interest in pneumatic circuits.

“Once a new technology becomes dominant, we lose awareness of other solutions to problems,” Grover said. “One thing I like about this research is that it can show the world that there are situations today when 100-plus-year-old ideas can still be useful.”

Source: University of California Riverside

Categories : Diseases, Syndromes and ConditionsTags :

First Test of Drug in a Patient with Rare Blood Clotting Disorder is a Success

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A team led by investigators from Massachusetts General Hospital, a founding member of the Mass General Brigham healthcare system, used a new drug to save the life of a patient with immune thrombotic thrombocytopenic purpura (iTTP), a rare disorder characterised by uncontrolled clotting throughout the small blood vessels. The group describes the first clinical use of the drug for iTTP in the New England Journal of Medicine.

“The drug is a genetically engineered version of the missing enzyme in iTTP, and we showed that it was able to reverse the disease process in a patient with an extremely severe form of this condition,” said lead author Pavan K. Bendapudi, MD, an investigator in the Division of Hematology and Blood Transfusion Service at Massachusetts General Hospital and an assistant professor of Medicine at Harvard Medical School.

iTTP results from an autoimmune attack against an enzyme called ADAMTS13 that is responsible for cleaving a large protein involved in blood clotting. The current mainstay of therapy for this life-threatening blood disorder is plasma exchange, which removes the harmful autoantibodies and provides extra ADAMTS13. Plasma exchange induces a clinical response in most patients but can restore at best only about half of normal ADAMTS13 activity. By contrast, a recombinant form of human ADAMTS13 (rADAMTS13) offers the possibility of greatly increased ADAMTS13 delivery.

rADAMTS13 was recently approved for patients with congenital thrombotic thrombocytopenic purpura, which occurs in patients born with complete loss of the ADAMTS13 gene. It’s questionable whether rADAMTS13 could be effective in iTTP given the presence of inhibitory anti-ADAMTS13 autoantibodies, but Bendapudi and his colleagues received permission from the US Food and Drug Administration to utilize rADAMTS13 donated from the manufacturer under a compassionate use protocol in a dying patient with treatment-resistant iTTP.

“We found that rADAMTS13 rapidly reversed this patient’s disease process despite the current dogma that inhibitory autoantibodies against ADAMTS13 would render the drug useless in this condition,” said Bendapudi. “We were the first physicians to use rADAMTS13 to treat iTTP in the United States, and in this case it helped to save the life of a young mother.”

Bendapudi noted that the infused rADAMTS13 overwhelmed the inhibitory autoantibodies in the patient and reversed the thrombotic effects of iTTP. This impact was observed almost immediately upon administration of rADAMTS13, after daily plasma exchange had failed to induce remission.

“I think rADAMTS13 has the potential to replace the current standard of care in acute iTTP. We will need larger, well-designed trials to evaluate this possibility,” said Bendapudi.

A phase 2b randomized clinical trial of rADAMTS13 in iTTP was recently initiated.

Source: Massachusetts General Hospital

Categories : Diseases, Syndromes and Conditions Obstetrics & GynaecologyTags :

Prescribed Oestrogen and Factor V Leiden Mutation More than Double Blood Clot Risk

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New research from Queen Mary University of London, published in iScience, shows an increased risk of blood clots in women who have any combination of Factor V Leiden gene mutation, oestrogen use, or common medical conditions – specifically: obesity, high blood pressure, high cholesterol, and kidney disease.

Women with the Factor V Leiden (FVL) gene mutation who had been prescribed oestrogen had more than double the risk of blood clotting compared to women who did not have this mutation. And almost 20% of the women who carry FVL, were prescribed oestrogen and had two medical conditions suffered a blood clot. The presence of the FVL gene made a substantial difference to risk, with only around 5% of women taking oestrogen and having two conditions suffering a clotting event.

The study also found that a woman with obesity, hypertension, high cholesterol, and kidney disease (not uncommon in a clinical setting) had an 8 times greater chance of blood clotting compared to a woman with none of these conditions. This amounted to roughly one in every six women with the four conditions in the study suffering a blood clot. Three medical conditions meant a five times greater chance of blood clotting, and two medical conditions meant a two times greater chance.

One in three women who had the FVL gene mutation and three of the medical conditions examined also suffered a blood clotting event.

The researchers examined the health data of 20 048 British-Bangladeshi and British-Pakistani women from the Genes & Health project, a large community-based genetics study. While oestrogen use, FVL, and common medical conditions are all known risk factors of blood clots, studies have not looked at the combined risk of these factors together on blood clot prevalence.

Women are commonly prescribed oestrogen, both through oral contraception containing the hormone and as part of post-menopausal hormone replacement therapy.

Professor Sir Mark Caulfield, from Queen Mary University of London, said: “Our study gives a more complete picture of blood clotting in Bangladeshi and Pakistani communities who have previously been underrepresented in research.

“Genetic testing of the FVL gene mutation could give a clearer sense of someone’s personalised risk of this potentially fatal complication if they were prescribed oestrogen.”

Source: Queen Mary University London

Categories : Cardiovascular Disease Metabolic DisordersTags :

New Research Points to Clot Lysis Protein for Cholesterol Control

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While high levels of low-density lipoprotein (LDL) can be reduced by drugs such as statins, reducing the risk of myocardial infarction and stroke, risk still remains in the form of other cholesterols. New research published in the journal Science describes how manipulating a protein involved in blood clot lysis could help bring cholesterol levels even more under control.

Heart disease remains a leading cause of death worldwide, despite advances in cholesterol-lowering medication such as proprotein convertase subtilisin-kexin type 9 inhibitors, which were approved by the FDA in 2015. One clinical trial following patients taking proprotein convertase subtilisin-kexin type 9 inhibitors demonstrated a benefit while also revealing an opportunity for improvement as the absolute risk reduction was considered modest at 1.5%.

“It is clear that there is more going on than just what statins and these newer inhibitor drugs can control,” says Ze Zheng, MBBS, PhD, MCW assistant professor of medicine. “More therapies are needed, and to get them we need to know more about other sources of risk for heart disease, especially heart attacks and strokes.”

So-called “bad cholesterol” is carried by apolipoprotein B (apoB) which forms well-structured particles with lipids and proteins. These particles serve as stable vehicles for transporting lipids such as cholesterol in the bloodstream. These lipid-rich particles mostly include very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL). Current cholesterol-lowering reduce mainly LDL levels, which though important to control, is not the only risk factor for heart disease. In fact, the other lipoproteins in the same group as LDL are not reduced by much with available treatments. Dr Zheng and her team are investigating how to reduce levels of other members of this family of lipoproteins, especially VLDL.

“With my background in lipid metabolism, I found myself consistently checking lipid levels even during studies regarding blood clot lysis and how an impairment in the body’s ability to remove blood clots affects the risk of blood vessel blockages,” Dr Zheng adds. “I was just naturally curious about it, and I noticed that a protein I was studying may have an effect on the amount of circulating cholesterol.”

In prior research, Dr Zheng has helped define a new cellular source of this protein, tissue-type plasminogen activator (tPA), and its role in breaking down blood clots and preventing blood vessel blockages. To understand its potential influence on cholesterol levels, her team used a gene-editing technique to stop liver cells from producing tPA in mice prone to blood vessel plaque formation. The scientists found that the mice developed increased lipoprotein-cholesterol in this experiment, and then validated the findings in follow-up studies using human liver cells and a type of rat liver cell known to produce VLDL in a way similar to human liver cells. With these and other experimental results, Dr Zheng and her team have demonstrated a new, important role that liver tPA influences blood cholesterol levels while underscoring a meaningful connection between the liver, heart and blood vessels.

“After defining this new role for tPA, we turned our attention to the question of how it changes blood cholesterol levels,” notes Wen Dai, MD, research scientist, Versiti Blood Research Institute.

The liver contributes to the majority of the “bad” apoB-lipoproteins by making VLDL. The team focused on whether and how tPA impacts the process of VLDL assembly in the liver. Microsomal triglyceride transfer protein (MTP) is required for the assembly of VLDL due to its role carrying lipids to the apoB. The scientists determined that tPA binds with the apoB protein in the same place as MTP. The more tPA is present, the fewer opportunities MTP has to connect with apoB and catalyse the creation of new VLDL. Essentially, MTP tries to pass a cholesterol to apoB, but tPA interferes with this pocess.

“Based on our prior research, we knew it also was critical to look at tPA’s primary inhibitor,” Dr. Zheng says.

Plasminogen activator inhibitor-1 (PAI-1) is known to block the activity of tPA. Scientists also have found a correlation between PAI-1 levels in blood and the development of disease due to plaque formation and blockages in blood vessels. The team found that higher levels of PAI-1 reduced the ability of tPA to bind with apoB proteins, rendering tPA less effective at competing with MTP to prevent VLDL production. Returning to the biological gridiron, PAI-1 might be a decoy receiver that distracts tPA until MTP connects with apoB for a big gain. The team studied this interaction in human subjects with a naturally occurring mutation in the gene carrying the code for PAI-1. The researchers found that these individuals, as predicted, had higher tPA levels and lower LDL and VLDL levels than individuals from the same community who did not have the same mutation.

“We are investigating therapeutic strategies based on these findings regarding tPA, MTP and PAI-1,” Dr Zheng notes. “I think we may be able to reduce the residual cardiovascular risk that has persisted even as treatment has advanced.”

Source: Medical College of Wisconsin

Categories : Cardiovascular DiseaseTags :

Scientists ‘Poke the Bear’ to Gain a Better Understanding of Blood Clotting

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Photo by Mark Basarab on Unsplash

It’s generally good advice not to “poke the bear” as they say, but that’s exactly what a multinational team of scientists have been doing, to discover the secrets of blood clotting. Hibernating bears, paralysed humans, and pigs kept in small enclosures all avoid dangerous blood clots, despite being immobile for extremely long periods.

Their new study published in Science shows that reduction of a key protein inhibits the formation of blood clots in all three mammal species when they are immobile for days, months or even years.

Passengers on long haul flights run the risk of developing deep vein thrombosis if they do not take some time to walk around and use compression socks. Some people are predisposed to blood clots, due to genetic factors.

Yet, when humans – and other mammals such as bears – are immobilised for a much longer period than a flight, the researchers found that a protein known as Hsp47 is reduced by 55 times. This could lead to new medicines to help those who have inherited blood clotting disorders that put them at risk for pulmonary embolism, heart attack, and stroke.

Professor Jon Gibbins led the work at the University of Reading. He said: “It seems counterintuitive that people who have severe paralysis don’t appear to be at higher risk of blood clots. This tells us that something interesting is happening. And it turns out that reducing levels of Hsp47 plays a key role in preventing clots, not just in humans, but in other mammals, including bears and pigs.

“When we see something like this in multiple species, that reinforces its importance. Having Hsp47 must have been an evolutionary advantage.”

Hsp47 is released by platelets – the sticky blood cells that trigger blood clotting.  Usually clotting is an important response to an injury, to prevent blood loss, and Hsp47 is one of the necessary ingredients to enable platelets to do their job. Examining the role of Hsp47 in clotting function the team found that when released into the blood of bears, mice and humans that it promoted conditions that may give rise to deep vein thrombosis.

Professor Gibbins said, “We aren’t totally sure how, but it appears that there is something about movement that keeps Hsp47 at an appropriate level. It could be that the mechanical forces involved in moving around actually have an impact on gene expression, dramatically increasing the amount of Hsp47 that circulates in the blood.”

The team took blood samples from bears in winter, while hibernating, and in summer, while awake and moving around. They also compared people who were immobilised with those who can move and walk. And finally, pigs kept in small pens were compared with others that were free to move around in barns. In all three cases, proteomics experiments showed that the absence of movement was associated with having far less Hsp47.

Professor Gibbins continued: “Now we know that Hsp47 is so important, we can begin to look for new or existing medicines that might be able to inhibit the function of this protein in blood clotting and protect mobile people who are prone to clots.”

Source: University of Reading

Categories : Metabolic DisordersTags :

Childhood Obesity is a Risk Factor for Blood Clots in Adulthood

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Being overweight in childhood and in early adulthood are discrete risk factors for blood clots (thrombi) later in life, according to a study using school health care and military service records, according to a study published in the Journal of Internal Medicine.

The association between obesity and blood clots is already established. However, to date it has been unclear how much influence a raised BMI in childhood and puberty exerts. Thrombi usually arise in the legs, often starting in a blood vessel in the calf. Swelling, pain and redness are common symptoms. Though easily treated if caught early, they can result pulmonary embolism may be life-threatening.

The present study comprises 37 672 men in Sweden, born between 1945 and 1961. It is based on information about height, weight, and BMI from the men’s records, first from school health care services (at the age of 8 years) and, second, from medical examinations on enrolment in the Armed Services (at age 20), along with register data on any blood clots up to age 62 on average.

Distinctly elevated thrombus risk

The results showed that BMI at both ages 8 and 20, independently of each other, can be linked to venous blood clots. These may occur in, for example, the leg (deep vein thrombosis, DVT) or the lung (pulmonary embolism).

In adulthood, two groups were found to be at a significantly increased risk of venous thrombi. The first was individuals who had been overweight both as children and as young adults, while the second was composed of those whose weight in childhood was normal and who became overweight only in early adulthood.

Moreover, being overweight in both childhood and young adulthood was found to raise the risk of arterial thrombi – clots resulting from constricted blood vessels with fatty deposits and inflammation. Since there were few cases of arterial blood clots in the study, however, further studies are needed to confirm these findings. All comparisons in the study were made with the control group, whose weight was normal at both 8 and 20 years of age.

Overweight in puberty an important factor

The first and corresponding author of the study is Lina Lilja, a doctoral student at Sahlgrenska Academy, University of Gothenburg, and paediatrician. At the time of the study, she worked at the Kungshöjd paediatric clinic in Gothenburg. Today, she is a senior physician in child health care in Region Västra Götaland.

“Our study shows that both overweight in childhood and overweight in young adulthood increase the risk of venous blood clots later in life. The latter, overweight when the men were young adults, proved to be a more influential factor than overweight when they were children,” Lilja notes.

The study includes data from the BMI Epidemiology Study (BEST) in Gothenburg, a population study, and from Swedish national registers.

Source: University of Gothenburg

Categories : Cardiovascular DiseaseTags :

Switch to Tenecteplase for Ischaemic Strokes Improves Outcomes and Lowers Costs

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Credit: American Heart Association

A newer, faster-administration clot-busting drug called tenecteplase outperforms the traditional treatment for ischaemic strokes in several key areas, including better health outcomes and lower costs, according to a new study published in the journal Stroke.

The 15-month study was led by a team of neurologists at Dell Medical School at The University of Texas at Austin.

“The Dell Med Neurology Stroke Program was one of the first in the United States to make this change,” said Steven Warach, MD, lead author of the study . “Based on even the earliest results from this study, other experts across the country were convinced and made the switch from alteplase to tenecteplase at their own stroke centres, including at Ascension hospitals nationwide.” 

The vast majority of strokes of the 800 000 strokes in the US (about 87%) each year are ischaemic.

Both tenecteplase and alteplase are federally approved for use in dissolving clots in blocked heart arteries. But the newer drug tenecteplase is also being used by clinicians, off-label, to treat ischaemic strokes, because clinical trials in stroke suggest that it may be at least as good as alteplase and it is easier to administer. Tenecteplase is administered by a single five- to 10-second intravenous injection. The researchers compared its performance with the standard drug for stroke, alteplase, which is injected over 60 minutes.

“When it comes to treating patients with a stroke, every second matters,” said Warach, who is also a professor of neurology at Dell Med. “The shorter preparation and injection time with tenecteplase not only eliminates a lot of dosing errors related to alteplase, but it’s also more efficient. We were able to deliver the clot-busting medicine more quickly after patients arrived in the emergency department, and for patients who needed to be transferred to another hospital for more advanced care after receiving the clot buster, we were able to initiate the transfer sooner in those treated with tenecteplase.”

For patients who come into the emergency department after a stroke, Warach’s study found that the “door-to-needle” time (from patients’ arrival to treatment) was on average six minutes quicker with tenecteplase. And for patients who also required a thrombectomy, the surgical removal of a blood clot causing the stroke, tenecteplase slashed to the time to transferring the patient to a thrombectomy-capable stroke centre by 25 minutes.

Researchers also saw improvements in clinical outcomes for patients given tenecteplase, including:

  • A 5% increase in patients who were able to walk independently at time of hospital discharge to home.
  • A 4% decrease in occurrences of bad events such as brain haemorrhages, discharge to hospice care or death.

The third major improvement: cost. The research team found that tenecteplase treatment cost the hospitals about US$ 2500 less than alteplase per patient.

Source: EurekAlert!

Categories : Cardiovascular DiseaseTags :

With Warfarin, Dropping Aspirin Reduces Bleeding Complications for Some

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Red blood cells
Source: Pixabay

Research from Michigan Medicine suggests that, for venous thromboembolism (VTE) or atrial fibrillation (AF) patients without a history of heart disease who are taking warfarin, stopping aspirin use causes their risk of bleeding complications to drop significantly.

For the study, which is published in JAMA Network Open, researchers analysed over 6700 people treated at anticoagulation clinics across Michigan for VTE as well as AF. Patients were treated with warfarin but also took aspirin despite not having history of heart disease.

“We know that aspirin is not a panacea drug as it was once thought to be and can in fact lead to more bleeding events in some of these patients, so we worked with the clinics to reduce aspirin use among patients for whom it might not be necessary,” said senior study author and cardiologist Geoffrey Barnes, MD.

Over the course of the study, aspirin use among patients fell by 46.6%. With aspirin used less commonly, the risk of a bleeding complication dropped by 32.3% – equivalent to preventing one major bleeding event per every 1000 patients who stop taking aspirin.

“When we started this study, there was already an effort by doctors to reduce aspirin use, and our findings show that accelerating that reduction prevents serious bleeding complications which, in turn, can be lifesaving for patients,” said Dr Barnes. “It’s really important for physicians and health systems to be more cognisant about when patients on a blood thinner should and should not be using aspirin.”

Several studies had found concerning links between concurrent use of aspirin and different blood thinners, which prompted this aspirin de-escalation.

One study reported that patients taking warfarin and aspirin for AF and VTE experienced more major bleeding events and had more ER visits for bleeding than those taking warfarin alone. Similar results were seen for patients taking aspirin and direct oral anticoagulants – who were found more likely to have a bleeding event but not less likely to have a blood clot.

“While aspirin is an incredibly important medicine, it has a less widely used role than it did a decade ago,” Dr Barnes said. “But with each study, we are seeing that there are far fewer cases in which patients who are already on an anticoagulant are seeing benefit by adding aspirin on top of that treatment. The blood thinner they are taking is already providing some protection from clots forming.”

For some people, aspirin can be lifesaving. Many patients who have a history of ischaemic stroke, heart attack or a stent placed in the heart to improve blood flow — as well as those with a history of cardiovascular disease — benefit from the medication.

The challenge comes when some people take aspirin without a history of cardiovascular disease and are also prescribed an anticoagulant, said first author Jordan Schaefer, MD.

“Many of these people were likely taking aspirin for primary prevention of heart attack or stroke, which we now know is less effective than once believed, and no one took them off of it when they started warfarin,” Dr Schaefer said. “These findings show how important it is to only take aspirin under the direction of your doctor and not to start taking over-the-counter medicines like aspirin until you review with your care team if the expected benefit outweighs the risk.”

Source: Michigan Medicine – University of Michigan

Categories : COVIDTags :

More Evidence Linking Blood Clotting and COVID Severity

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Source: CC0

New research shows that the Omicron variants cause significantly lower levels of blood clotting, thereby providing further evidence for the link between the severity of the disease and the prevalence of persistent micro blood clots in individuals with acute and Long COVID.

Prof Resia Pretorius, a researcher in the Department of Physiological Sciences at Stellenbosch University (SU), South Africa, first made this connection late in 2020 when she detected small amyloid-like blood clots in the plasma of individuals suffering from COVID. Amyloids are a type of protein associated with various inflammatory diseases. As part of a long-term collaboration with Prof Douglas Kell from the University of Liverpool, they showed that these micro clots contained pro-inflammatory molecules. The results of both studies were published in the journal Cardiovascular Diabetology, in 2020 and 2021.  

These insoluble micro clots inhibit or may temporarily block blood flow to capillaries and hence impair oxygen transfer to tissues. At present, they believe that this oxygen impairment in various parts of the body can account for most of the symptoms of Long COVID, such as constant fatigue, shortness of breath, brain fog, joint and muscle pain.

Prof Resia Pretorius

Prof Pretorius said the persistent prevalence of micro clots may have significant clinical value: “Our findings suggest that hypercoagulation and vascular damage are key role players causing the wide range of symptoms we see in patients with Long COVID. There is a golden thread running through pathologies noted in post-viral syndromes such as Long COVID.”

More recently, Prof Pretorius and Prof Kell worked with a team of clinicians in South Africa and the United States, to ascertain whether the difference in the degree of clotting between different viral strains of the SARS-CoV-2 virus provides a plausible explanation for the relatively low severity of the Omicron variants during acute COVID infection.

While the earlier variants caused severe disease and critically ill patients, the heavily mutated Omicron variants have been shown to have milder symptoms, most commonly a runny nose, rhinitis headaches, fatigue (from mild to severe), sneezing and a sore throat.

For the purposes of the study, they revisited data and blood samples from stored blood samples from ten patients with COVID due to the Beta and Delta variants between October 2020 and September 2021 before the patients received treatment.

The team also collected blood from patients infected with the Omicron variants. In all ten samples it was found that the Omicron samples presented with a significantly lower total amount of microclots compared to earlier Beta and Delta variants.  

In a recent webinar on the topic, Dr Mark Walsh, an emergency medicine physician at the Saint Joseph Regional Medical Center in the United States of America, said the foundational work of Profs Pretorius and Kell has helped them to explain the clotting complications of COVID-induced coagulopathies (CAC) of patients with acute COVID. He is also one of the co-authors on the article.

“We could not understand why patients with CAC would clot and bleed at the same time. We now have the pathophysiological foundation for a point-of-care bedside medicine approach, based on the foundations of excellent research,” he said.

Early in the pandemic, Dr Walsh and his team of emergency physicians in the USA, developed a protocol to provide safe anticoagulation treatment to severely ill COVID patients. The team was guided by thromboelastography, a point-of-care protocol to monitor bleeding and clotting.

According to Prof Kell, more importantly, the findings are consistent with the view that these insoluble micro clots are not a side-effect of COVID-19, but a part of how the disease develops. However, he warned, we do not yet know how this will impact or relate to other post-viral syndromes such as Long-COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), post-Zika or post-Dengue diseases.

The paper, titled “Relative hypercoagulopathy of the SARS-CoV-2, Beta and Delta variants when compared with the less severe Omicron variants is related to TEG parameters, the extent of fibrin amyloid microclots, and the severity of clinical illness” is in press in the journal Seminars in Thrombosis and Hemostasis, and a preprint is available at https://www.researchsquare.com/article/rs-1970823/v1

The webinar, “COVID-induced Coagulopathy (CAC): The clot thickens…or not?” is presented by Dr Mark Walsh, Prof Resia Pretorius and Prof Douglas Kell, and moderated by Dr Asad Khan. It is available at https://youtu.be/yyf7xunWydM

Categories : COVID GeneticsTags :

Rare COVID Vaccine Blood Clots May Result from Genetics

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Photo by Spencer Davis on Unsplash

Scientists have discovered that the rare blood clot side-effect associated with some COVID vaccines could be the result of a specific gene variant, which could make a genetic screening test possible.

Vaccine-induced thrombotic thrombocytopenia (VITT), a rare disorder causing thrombosis and thrombocytopenia (low blood platelet counts), was linked to AstraZeneca’s COVID vaccine in early 2021, leading some countries to pause or restrict its use. It is also associated with the Johnson & Johnson vaccine, which also uses a viral vector.

Now, a new study may help to explain what’s causing the rare side effect. The study by Flinders University and SA Pathology is now available on the medRxiv preprint server and is awaiting peer review.

Examining five unrelated individuals who all had the clotting complication after vaccination, the researchers found that all of the patients had unusually structured antibodies against a protein called platelet factor 4 (PF4), which is involved in blood clotting.

In addition, all five shared a specific version of a gene responsible for producing these antibodies.

“We knew previously that PF4 was directly involved in the clotting disorder, and we knew that aberrant antibodies against PF4 are responsible, but what we don’t know is how and why some people develop them,” explained lead author Dr Jing Jing Wang.

The antibodies were all found to be derived from the same amino acid sequence. The researchers then found that all of the patients carried a specific variant of one gene, called IGLV3-21*02, most commonly occurring in people of European descent.

“The other specific amino acid sequences of these antibodies from each patient were derived from separate basic sequences but had all evolved to carry very similar properties, making them very potent attackers of the PF4 protein,” explained research team leader Professor Tom Gordon.

“Together, this suggests that it is the combination of a variant in a gene and the evolution of this antibody towards targeting the PF4 protein in a destructive manner, which is leading to this harmful side-effect.”

Though why the antibody is found in such a tiny number of vaccine recipients remains unknown, the identification of the gene could enable a genetic screening tool to identify patients who are at risk of this severe complication.

“It also provides a unique opportunity for targeted, specific therapy development aimed at neutralising this highly damaging but very specific antibody,” said Dr Wang.

Source: Flinders University