Category: Cardiovascular Disease

Categories : Cardiovascular DiseaseTags :

A Nearly Five-fold Increase in Hospitalisations for Common Cause of Stroke

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Ischaemic and haemorrhagic stroke. Credit: Scientific Animations CC4.0

Cervical artery dissection is a tear in an artery in the carotid or vertebral artery, and can result in blood clots that cause stroke. A new study has found almost a five-fold increase in the number of U.S. hospitalisations for cervical artery dissection over a 15-year period. The study is published on April 2, 2025, online in Neurology®, the medical journal of the American Academy of Neurology (AAN).

A dissection in the artery wall is most often caused by trauma due to motor vehicle accidents but can also occur with smaller injuries. Heavy lifting has also been shown to cause dissection in some people.

“Cervical artery dissection is an important cause of stroke, especially in people under 50, so it is crucial to detect it right away,” said Shadi Yaghi, MD, of Brown University in Providence, Rhode Island. “Strokes that are not fatal can lead to long-term disability, poor mental health and reduced quality of life. Our research found a dramatic increase in the number of hospitalisations for cervical artery dissection with rates rising steadily year over year.”

For the study, researchers reviewed 15 years of U.S. health data to identify 125 102 people hospitalised for cervical artery dissection. Participants had an average age of 51, and just over half had a stroke at the same time as dissection. Of all participants, 65% were white, 10% were Black, 8% were Hispanic, 3% were Asian or Pacific Islander, and 14% were of other racial groups. Researchers compared the number of hospitalisations to U.S. Census data to determine the annual rate of cervical artery dissections. They then calculated the average annual percentage change in those rates.

Researchers found the number of dissections increased from 11 cases per one million people in 2005 to 46 cases per one million people in 2019, with an average annual increase of 10%. Results were similar for both female and male participants. The average annual increase for Hispanic participants was 16%; for Black participants it was 13%, Asian participants, 12% and white participants, 8%.

Researchers also found a greater average annual increase among people 65 and older at 12% compared to 8% for people under 65.

“Possible reasons for this nearly five-fold increase over 15 years include greater awareness of cervical artery dissection by health care professionals, better access to imaging to help identify it and an overall increase in this condition for which a cause has yet to be determined,” said Yaghi. “Given the rising incidence of cervical artery dissection, our study underscores the importance of finding prevention strategies as well as new treatments to reduce the risk of stroke.” A limitation of the study was that the hospital admission data does not include undiagnosed or untreated cases, so the number of cases may be even higher.

Source: American Academy of Neurology

Categories : Cardiovascular Disease ExerciseTags :

Preventable Cardiac Deaths during Marathons are Down

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Photo by Barbara Olsen on Pexels

While more people than ever are running marathons in the U.S., the risk of dying from a heart attack during a run has fallen dramatically in recent years. That’s a key conclusion from a new study by Jonathan Kim, associate professor in the Emory School of Medicine. Kim’s research is a follow-up to a study he published in 2012 — the first investigation into unexpected cardiac arrests during long distance running events.

The new findings, published in JAMA, indicate that, while the rate of marathon runners who suffer cardiac arrests remained unchanged, their chance for survival is twice what it was in the past. Far fewer marathon runners who suffer cardiac arrest are now dying of it.

“We continue to see media reports about unfortunate cases of cardiac arrest during long distance running events,” Kim says. “But, has the incidence of these events changed? Have there been changes in the most common causes of cardiac arrest? What are the factors associated with death and survival? It was a novel question to ask 13 years after our first analysis, and an important one because recreational running continues to increase in popularity.”

The challenge of finding data

More than 29 million people completed marathons in the U.S. between 2010 and 2023, triple the number of the previous decade, which Kim examined in his first study. There’s no central registry of race-related cardiac events, so for both studies, his team had to find their data through a range of sources, starting by contacting individual race directors.

“We leveraged a few sources including a comprehensive review of media reports,” Kim says. “We also had contact information for all race directors and were able to reach approximately 70% of them who helped and told us the number of events during this specific timeline, including if the individual died and the sex of the participant.”

The researchers used extensive public internet searches to identify and reach out to runners who survived cardiac arrests or next-of-kin to construct detailed profiles of as many cases as possible. “The vast majority of cases were identifiable by public search engines. And all of the deaths were as well,” he says.

Analyzing this extensive database, Kim found that while the rate of cardiac arrests was about the same during the two periods — .60 per 100 000 participants now versus .54 per 100 000 participants in the earlier period — the rate of deaths from these cases, however, fell by half: from .39 per 100 000 to .19 per 100 000. That’s about a 50% decline in the death rate since 2000–2009. As before, cardiac arrests remained far more common among men than among women and more common in marathons than half marathons.

The sport’s growing awareness of cardiac death risk

What led to the dramatic change in death rates? Kim thinks the whole sport has become more aware of the risks and of the need to have emergency services available to runners, a conclusion he reached after interviewing as many survivors as he could find. “What we found was that every one of those people got hands-on cardiopulmonary resuscitation, but the vast majority also had immediate access to an automated external defibrillator. That’s the difference,” he says.

That survival rate is comparable to the cardiac arrest survival rate in other public places that now make defibrillators routinely available such as airport and casinos, which have seen similar declines in deaths.

Kim says his findings offer additional evidence of how important it is to make CPR training available to race participants and to strategically place defibrillators along the racecourse. It’s also important, he says, to better identify the most vulnerable in a population before they run a race.

“These are more often potentially preventable events,” he says. “Being able to identify people, more commonly older individuals with unrecognized cardiovascular risk factors, doesn’t mean they can’t run a race. Rather, it affords the opportunity to improve primary preventive cardiovascular care and potentially further reduce the risk of cardiac arrest during these events. The incidence of sudden cardiac arrest during long-distance races hasn’t changed in over twenty years. I think this is an important arena of future research.”

Source: Emory Health Sciences

Categories : Cardiovascular DiseaseTags :

Possible Link Between Medication and Unexpected Blood Clots

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Thrombophilia. Credit: Scientific Animations CC4.0.

Why do medications that are supposed to help patients with chronic inflammatory diseases sometimes lead to blood clots? This is one of the questions that a team of researchers from Aarhus University has sought to answer in a study that has just been published in the journal Inflammopharmacology.

The study suggests that disturbances in the JAK-STAT signalling pathway, an important communication pathway in the body, may contribute to this side effect.

“In the study, we uncover the potential links between components of the JAK-STAK signalling pathway, blood markers in patients with blood clots, and the genetic factors that contribute to the risk of blood clots in patients. This helps improve our understanding of why we see an increased risk of blood clots when using JAK inhibitors,” explains Stine Rabech Haysen, former medical student at the Department of Biomedicine at Aarhus University, who is the first author of the publication. 

The potential of the study

In the study, researchers used publicly available data from a number of published studies about patients with blood clots and compared them with a healthy control group.

They found no direct genetic explanation, but they did find a statistically significant enrichment of genes that are subject to regulatory control of the JAK-STAT signalling pathway among genes whose expression is altered in patients with blood clots.

“Although we cannot draw definitive conclusions about the mechanistic link between the use of JAK inhibitors and the risk of blood clots, our study demonstrates the potential of using data mining to identify and shed light on possible mechanisms of drug side effects,” says one of the study’s senior authors, associate professor at the Department of Biomedicine Per Qvist.

What does this mean for patients?

Although JAK inhibitors rarely lead to blood clots, it’s important to understand the mechanism behind them so that the risk can be reduced.

“For the average person, our study means that we’re getting closer to understanding why some drugs can have dangerous side effects like blood clots. And going forward, our method could help identify and prevent serious side effects, potentially making drug treatment safer,” explains the other senior author of the study, associate professor at the Department of Biomedicine Tue Wenzel Kragstrup.

The researchers will now test the method on other types of medication to see if it can be used to detect side effects more widely.

Source: Aarhus University

Categories : Cardiovascular DiseaseTags :

Despite Heart Failure Improvement, Continued Medication is Important

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Photo by Towfiqu Barbhuiya on Unsplash

Patients who have been treated for heart failure and experience an improvement of their pump function, are still at higher risk of heart-related death or hospitalisation if they stop taking heart failure medications. This is according to a new study from Karolinska Institutet published in Circulation.

“Our finding raises awareness about the importance of implementing and not withdrawing medical treatments in daily clinical practice even if patients with heart failure experience an improvement in symptoms and pump function,” says the study’s last author Gianluigi Savarese, docent and senior lecturer at the Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, and senior cardiologist at Södersjukhuset. 

Using data from the Swedish Heart Failure Registry, RiksSvikt, the researchers have analysed more than 8700 patients with heart failure whose heart pump function, the ejection fraction, was initially impaired (below 40%) but later improved to 40% or more.  

By linking RiksSvikt with other national registers, the researchers from Karolinska Institutet and Linköping University, Sweden, and the University of Naples, Italy, among others, were able to track hospitalisations and deaths in patients who stopped or continued various heart failure treatments. 

Increased morbidity and mortality 

The observational study shows that patients who stopped taking medication of the type RASi (renin-angiotensin system inhibitors), ARNi (angiotensin receptor-neprilysin inhibitors) or MRA (mineralocorticoid receptor antagonists) had between 36 and 38% higher risk of heart-related death or hospitalisation within one year of medication discontinuation.  

However, stopping beta-blocker medication was only associated with a higher risk in patients whose heart function had only moderately improved. 

“Our results show that heart failure medications continue to provide important benefits even when heart function has improved,” says Gianluigi Savarese. “This supports the current recommendation to continue with RASi/ARNi and MRA treatment, but also opens up the possibility of reconsidering whether beta-blockers can be discontinued in certain patients whose heart function has recovered well.” 

More tailored treatment strategies 

Since it was an observational study, no firm conclusions can be drawn about causality. It cannot be ruled out that the results were influenced by residual confounding. The researchers are now planning further studies to confirm the results. 

“Our goal is to understand how heart failure medications affect patients with improved heart function and to develop guidelines for when/if it is safe to discontinue certain treatments. This can lead to more tailored and effective treatment strategies for heart failure patients,” says Christian Basile, the study’s first author and PhD student in Gianluigi Savarese’s research group.  

Source: Karolinska Institutet

Categories : Cardiovascular Disease Substance UseTags :

Substantially Higher Risk of Heart Attack in Cannabis Users

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Photo by Thought Catalog on Unsplash

Marijuana is now legal in many places, but is it safe? Two new studies add to mounting evidence that people who use cannabis are more likely to suffer a heart attack than people who do not use the drug, even among younger and otherwise healthy adults. The findings are from a retrospective study of over 4.6 million people published in JACC Advances and a meta-analysis of 12 previously published studies being presented at the American College of Cardiology’s Annual Scientific Session.

Marijuana use has risen in the United States, especially in states where it is legal to buy, sell and use the drug recreationally. In the retrospective study, researchers found that cannabis users younger than age 50 were over six times as likely to suffer a heart attack compared to non-users. The meta-analysis, which is the largest pooled study to date examining heart attacks and cannabis use, showed a 50% increased risk among those who used the drug.

“Asking about cannabis use should be part of clinicians’ workup to understand patients’ overall cardiovascular risk, similar to asking about smoking cigarettes,” said Ibrahim Kamel, MD, clinical instructor at the Boston University Chobanian & Avedisian School of Medicine and internal medicine resident at St. Elizabeth Medical Center in Boston and the study’s lead author. “At a policy level, a fair warning should be made so that the people who are consuming cannabis know that there are risks.”

Kamel and his team conducted the retrospective study using data from TriNetX, a global health research network that provides access to electronic medical records. Their findings indicate that over an average follow-up of over three years, cannabis users had more than a sixfold increased risk of heart attack, fourfold increased risk of ischaemic stroke, twofold increased risk of heart failure and threefold increased risk of cardiovascular death, heart attack or stroke. All study participants were younger than age 50 and free of significant cardiovascular comorbidities at baseline, with blood pressure and low-density lipoprotein (LDL) cholesterol levels within a healthy range and no diabetes, tobacco use or prior coronary artery disease.

For the meta-analysis, the researchers pooled data from 12 previously published research studies that collectively included over 75 million people. The studies were rated as being of moderate to good quality in terms of methodology. Of the 12 studies, 10 were conducted in the United States, one in Canada and one in India. Some of the studies did not include information about participants’ ages, but the average age was 41 years among those that did, suggesting that the pooled sample reflected a relatively young population.

Taken individually, seven of the studies found a significant positive association between cannabis use and heart attack incidence, while four showed no significant difference and one showed a slightly negative association. When the researchers pooled the data from all studies and analysed it together, they found a significant positive association, with active cannabis users being 1.5 times as likely to suffer a heart attack compared with those who aren’t current users.

Cannabis use and heart attack incidence was assessed in a similar manner across the different studies. However, due to inconsistencies in the data available from each study, researchers were unable to account for several potential confounding factors including the duration and amount of cannabis use or the use of tobacco or other drugs. 

“We should have some caution in interpreting the findings in that cannabis consumption is usually associated with other substances such as cocaine or other illicit drugs that are not accounted for,” Kamel said. “Patients should be forthcoming with their doctors and remember that we are their number one advocate and having the full story matters.”

While the mechanisms through which marijuana or its components may impact the cardiovascular system are not fully understood, the researchers hypothesize that it can affect heart rhythm regulation, heighten oxygen demand in the heart muscle and contribute to endothelial dysfunction, which makes it harder for the blood vessels to relax and expand, and can interrupt blood flow. One of the studies included in the meta-analysis found that the risk of heart attack peaked about one hour after marijuana consumption.

Since both studies were limited by their retrospective nature and the meta-analysis was limited by the challenges inherent in pooling data from multiple studies, researchers said that additional prospective studies would help to confirm the findings and determine which groups may face the highest risk. 

A previous study presented at the American College of Cardiology’s Annual Scientific Session in 2023 found that daily marijuana use was associated with an increased risk of developing coronary artery disease. 

The retrospective analysis will simultaneously publish in JACC Advances.

Source: American College of Cardiology

Categories : Cardiovascular DiseaseTags :

Breakthrough Research Offers Hope for Ischaemic Heart Failure

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Right side heart failure. Credit: Scientific Animations CC4.0

Researchers report a groundbreaking discovery in cardiac regeneration that offers new hope for the treatment of ischaemic heart failure. Published in npj Regenerative Medicine, the study reveals a novel approach to promoting cardiomyocyte proliferation.

The paper was authored by researchers at Baylor College of Medicine, the QIMR Berghofer Medical Research Institute in Brisbane, Australia, and collaborating institutions.

“When the heart cannot replace injured cardiomyocytes with healthy ones, it becomes progressively weaker, a condition leading to heart failure. In this study, we investigated a new way to stimulate cardiomyocyte proliferation to help the heart heal,” said co-corresponding author Dr Riham Abouleisa, assistant professor in the Division of Cardiothoracic Surgery at Baylor.

Previous studies showed that calcium plays an important role in cardiomyocyte proliferation. In the current study, Abouleisa and her colleagues explored how modulating calcium influx in cardiomyocytes would affect their proliferation.

“We found that preventing calcium influx in cardiomyocytes enhances the expression of genes involved in cell proliferation,” Abouleisa said. “We prevented calcium influx by inhibiting L-Type Calcium Channel (LTCC), a protein that regulates calcium in these cells. Our findings suggest that LTCC could be a target for developing new therapies to induce cardiomyocyte proliferation and regeneration.”

The study demonstrates that both pharmacological and genetic inhibition of LTCC can induce cardiomyocyte replication and that this occurs by modulating the activity of calcineurin, a known regulator of cardiomyocyte proliferation. This innovative approach showed promising results both in human cardiac slices grown in the lab and in live animals.

Abouleisa and her colleagues’ research highlights the importance of targeting calcium signalling pathways to unlock the regenerative potential of the heart and opens new avenues for developing cardiac regenerative therapies, potentially transforming the treatment landscape for patients suffering from heart failure.

Source: Baylor College of Medicine

Categories : Cardiovascular Disease Mental HealthTags :

In Younger Women, Stress is Associated with an Increased Stroke Risk

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Credit: American Heart Association

Some people living with chronic stress have a higher risk of stroke, according to a study published on online in Neurology®, the medical journal of the American Academy of Neurology. The study looked at younger adults and found a correlation between stress and stroke, with no known cause, in female participants, but not male participants.

“Younger people often experience stress due to the demands and pressures associated with work, including long hours and job insecurity, as well as financial burdens,” said Nicolas Martinez-Majander, MD, PhD, of the Helsinki University Hospital in Finland.

“Previous research has shown that chronic stress can negatively affect physical and mental health. Our study found it may increase the risk of stroke in younger women.”

For the study, researchers looked at 426 people aged 18 to 49 who had an ischaemic stroke with no known cause. They were matched for age and sex with 426 people who did not have stroke. Participants completed a questionnaire about stress levels over a one-month period. Those with stroke were asked after their stroke to record stress levels in the month prior to their stroke.

Participants were asked 10 questions, such as “In the last month, how often have you felt that you were unable to control the important things in your life?” Scores for each question ranged from zero to four, with four meaning “very often.” A total score of 0 to 13 represented low stress; 14 to 26, moderate stress; and 27 to 40, high stress.

Those with stroke had an average score of 13 compared to those without stroke who had an average score of 10. People with stroke were more likely to have at least moderate stress levels. Of those with stroke, 46% had moderate or high stress levels compared to 33% of those who did not have stroke. After adjusting for factors that could affect risk of stroke such as education level, alcohol use and blood pressure, researchers found for female participants, moderate stress was associated with a 78% increased risk of stroke and high stress was associated with a 6% increased risk.

Researchers did not find a link between stress and stroke in male participants. “More research is needed to understand why women who feel stressed, but not men, may have a higher risk of stroke,” said Martinez-Majander.

“In addition, we need to further explore why the risk of stroke in women was higher for moderate stress than high stress. Knowing more about how stress plays a role could help us to create better ways to prevent these strokes.”

A limitation of the study was that people experiencing higher levels of stress may have been less likely to enrol in the study, which could have affected the results.

Source: American Academy of Neurology

Categories : Cardiovascular DiseaseTags :

New Study Supports Caution on Corticosteroids Use in Lupus Heart Condition

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Human heart. Credit: Scientific Animations CC4.0

A new study of more than 2900 patients provides evidence that it’s likely best to use as little corticosteroid medicine as possible when treating people who have lupus pericarditis, a common heart complication of the autoimmune disease Systemic Lupus Erythematosus (SLE).

This study, funded by the National Institutes of Health’s (NIH) National Heart, Lung, and Blood Institute (NHLBI) and led by Johns Hopkins Medicine cardiologists and rheumatologists who led the study say their analysis of data affirms that using steroids to curb heart inflammation and other painful symptoms for lupus patients is also a risk factor for recurring pericarditis,.  

Results of this study were published in JAMA Network Open.

The American Heart Association defines pericarditis as inflammation of the pericardium, the twin-layered sac-like structure surrounds the heart to hold it in place and help protect it. Pericarditis typically presents as chest pain that can be exacerbated by lying flat and improved by leaning forward. This pain can last anywhere from a few days to several months. Treatment options for pericarditis include use of colchicine, an anti-inflammatory medication that prevents the recurrence of pericarditis, and corticosteroids.

Pericarditis occurs in 15% to 30% of patients with SLE, a chronic autoimmune disease that causes the body’s immune system to attack its own tissues. “It is well known that, in the general population, one fifth of patients who experience pericarditis end up experiencing one or more recurrences. Surprisingly, even though pericarditis is the most common cardiac complication of Lupus, we could not find any information on recurrent of pericarditis in this patient population,” says Dr Luigi Adamo, MD, PhD, director of Cardiac Immunology at Johns Hopkins University and co-senior author of this study.

Researchers set out to address this gap in knowledge and examine the risk factors contributing to the recurrence.

For the new analysis, researchers used data gathered among the Hopkins Lupus Cohort, a large ongoing study group that includes information on 2,931 patients diagnosed with SLE between 1988 to 2023 and the investigators focused on data from 590 patients also diagnosed with pericarditis. Pericarditis in the data set was identified using the Safety of Estrogens in Lupus Erythematosus National Assessment – SLE Disease Activity Index (SELENA-SLEDAI), a standard tool in the assessment of SLE clinical activity.   

Study results showed that 20% of patients with Lupus who experienced pericarditis had a recurrence. Recurrent pericarditis was most prevalent among patients within the first year of pericarditis onset, with recurrence decreasing in the following years. Younger patients and those with uncontrolled disease were at greater risk of recurrence. It was noted that oral prednisone therapy, a tool frequently used to treat pericarditis in patients with autoimmune diseases, was associated with a higher chance of pericarditis recurrence in patients with SLE.

“The cardiology literature has shown that use of corticosteroids increases the risk of recurrent pericarditis in the general population. Nevertheless, steroids are very frequently used by rheumatologists to treat lupus pericarditis. Therefore, the findings from this study underscore the importance of minimising oral corticosteroid use in patients with lupus and indicate the need for alternative strategies.” said Andrea Fava, MD, a rheumatologist who specialises in care of patients with lupus and co-senior author of the study.

Source: Johns Hopkins Medicine

Categories : Cardiovascular Disease New Compounds and TreatmentsTags :

New Drug may Delay Need for Aortic Valve Surgeries by Slowing Disease Progression

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Artificial heart valve. Credit: Scientific Animations CC4.0

Researchers at Mayo Clinic are exploring the use of a new drug called ataciguat to manage aortic valve stenosis (AVS). Results from preclinical and clinical studies, published in Circulation, show that ataciguat has the potential to significantly slow disease progression. The final step to establish the drug’s long-term effectiveness and safety is a phase 3 trial, and efforts to launch that pivotal trial are soon to be underway with an industry partner.

In AVS, calcium deposits build up and narrow the aortic valve, forcing the heart to work harder to move blood. The condition typically progresses over time, with symptoms like chest pain, shortness of breath and fatigue affecting people over age 65. The current standard of care, watchful waiting, often leads to reduced quality of life before the condition is severe enough for the patient to have a surgical or interventional valve replacement.

“This research represents a significant advancement in the treatment of aortic valve stenosis,” says Jordan Miller, PhD, director of the Cardiovascular Disease and Aging Laboratory at Mayo Clinic.  “Ataciguat has the potential to substantially delay or even prevent the need for valve replacement surgery, significantly improving the lives of millions.”

Dr Miller notes that the impact extends beyond simply delaying surgery. Younger patients with aggressive disease or congenital valve defects may develop symptoms in midlife. If a patient requires valve replacement before the age of 55, there is a more than 50% likelihood they will require multiple valve replacement surgeries over their lifetime due to recalcification of the implanted valve. Ataciguat, which slowed progression of native aortic valve calcification in the clinical trial, offers the potential for a once-in-a-lifetime procedure if they can reach the age of 65. The older a patient is, the less likely the implanted valve is to calcify.

Over the past decade, Mayo Clinic’s research revealed that ataciguat reactivates a pathway crucial in preventing valvular calcification and stenosis. Preclinical studies in mice showed that this drug substantially slowed disease progression even when treatment began after the disease was established.  

Clinical trials in patients with moderate AVS demonstrated that once-daily ataciguat dosing was well tolerated, with minimal side effects compared to placebo. This latest phase 2 trial in 23 patients showed a 69.8% reduction in aortic valve calcification progression at six months compared to placebo, and patients receiving ataciguat tended to maintain better heart muscle function. Crucially, the research team confirmed that, despite its profound effect on slowing valve calcification, ataciguat did not negatively impact bone formation.

Source: Mayo Clinic

Categories : Cardiovascular DiseaseTags :

New Treatment-resistant Blood-clotting Disorder Identified

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Thrombophilia. Credit: Scientific Animations CC4.0.

Researchers at McMaster University have made a groundbreaking discovery in the field of haematology, providing an explanation for spontaneous and unusual blood-clotting that continues to occur despite treatment with full-dose blood thinners.

The discovery, published in The New England Journal of Medicine, is expected to influence how doctors test for, and treat patients with, unusual or recurrent blood clotting, with the potential to improve patient outcomes.

Researchers found this new blood clotting disorder to have certain similarities to vaccine-induced immune thrombocytopenia and thrombosis (VITT) – a rare but aggressive clotting disorder that was caused by certain discontinued COVID-19 vaccines.

The research reveals that certain patients can develop severe blood clotting due to antibodies that closely resemble those that cause VITT, even in the absence of known triggers for such antibodies, such as blood thinners (heparin) or prior vaccination.

The newly identified disorder has been termed VITT-like monoclonal gammopathy of thrombotic significance (MGTS).

“Our study highlights the importance of recognising and diagnosing this new blood-clotting disorder,” said Theodore (Ted) Warkentin, co-first author and corresponding author of the study and professor emeritus in the Department of Pathology & Molecular Medicine at McMaster University.

“By understanding how to diagnose VITT-like MGTS, we can develop more effective treatment strategies that go beyond traditional anticoagulation,” said Warkentin, a hematologist in the Department of Medicine based at Hamilton Health Sciences’ Hamilton General Hospital.

Specialized testing was conducted at the McMaster Platelet Immunology Laboratory within the Michael G. DeGroote Centre for Transfusion Research, the only laboratory in Canada with the full repertoire of testing required to characterize the VITT-like antibodies that target the PF4 protein. Researchers performed a detailed analysis of cases exhibiting unusual blood-clotting despite patients being on full-dose blood thinners, focusing on those patients who had unexplained VITT-like antibodies that were detectable for a year or more.

The analyses identified the presence of M (monoclonal) proteins (which typically indicate plasma cell disorders), and together with the persisting VITT-like reactivities over at least 12 months (which is highly unusual for most anti-PF4 antibodies), thus pointing to an ongoing pathological process rather than a short-term anomaly.

The study included a multinational collaboration, with data collected from five patients treated at institutions in Canada, New Zealand, France, Spain, and Germany.

Collaborator Jing Jing Wang of Flinders University in Australia played a crucial role in proving for each patient that the M proteins are the pathological VITT-like antibodies. Collaborator Andreas Greinacher of Greifswald University in Germany helped in identifying similar cases in his anti-PF4 reference lab.

“The findings of this study underscore our ability to leverage fundamental molecular and biochemical science to unravel disease mechanisms,” said Ishac Nazy, co-lead author of the study and scientific director of the McMaster Platelet Immunology Laboratory and co-director of the Michael G. DeGroote Centre for Transfusion Medicine.

“This approach enables precise patient diagnosis and informs timely treatment strategies, even for previously unidentified diseases, exemplifying true bench-to-bedside translational medicine,” said Nazy, associate professor in the Department of Medicine at McMaster.

A remarkable observation was that each of the patients had failed blood thinning treatment, but they showed some benefit with unusual treatments, such as high-dose intravenous immunoglobulin (IVIG), Bruton tyrosine kinase inhibitors (ibrutinib), and plasma cell–targeted myeloma therapy. The existence of this novel blood clotting disorder has important implications for how health care providers will evaluate patients who develop unusual or difficult to treat blood clots in the future.

Source: McMaster University