March 11, 2025 | A new platelet function test has been developed by researchers in the UK that could help pharmaceutical companies design better, safer drugs for the prevention of heart attacks and strokes and, longer term, to help doctors know which of their high-risk patients should be put on blood thinners. Ultimately, the test could be developed into a point-of-care preventive diagnostic for the general population that’s as simple to use as a blood glucose fingerprick test, according to Jon Gibbins, Ph.D., professor of cell biology and director of the Institute for Cardiovascular and Metabolic Research at the University of Reading and chief scientific officer of the new spin-out company HaemAnalytica.
It has been nicknamed the TRIPLE Score (Thrombotic Reactivity Indicator using Platelet GPVI, CD36 [cluster of differentiation 36] Expression, and age) and was found to provide a useful biomarker of thrombus formation in a study that was published recently in Circulation Research (DOI: 10.1161/CIRCRESAHA.124.325701). Results align with existing cardiovascular risk scores—based on common, often self-measured factors such as height, weight, blood pressure, and cholesterol level—used to predict patients’ likelihood of having a heart attack in the next 10 years absent from the information on platelet function.
In that sense, the study validated the relationship between increased platelet reactivity and cardiovascular events. The evidence for the linkage has up to now been “very limited,” points out Alex Bye, Ph.D., lecturer in pharmacology at the University of Reading and lead author of the study. TRIPLE Score could become a method for stratifying patients based on this platelet function phenotype, enabling the identification of high-risk patients best suited for antiplatelet therapy.
For people who have already had a heart attack or stroke, the benefits of taking blood-thinning medications (e.g., aspirin and clopidogrel) are often thought to be well worth the risk of excessive bleeding, he says. But up until quite recently, people with risk factors but no prior event were also automatically prescribed platelet-targeting medications despite the inability to distinguish between people with high and low platelet function and thus properly make the risk-benefit calculation.
The quandary today is how to decide which high-risk individuals should get antiplatelet drugs, and this is where the TRIPLE Score could initially find clinical utility, says Bye. More immediately, the test could be used in support of industry-sponsored clinical trials. Although HaemAnalytica only launched in early February, the company is already working with several companies on the laboratory work that happens upstream of trials, he notes.
Its specialty is platelet analysis, which has relevance across disease areas beyond cardiovascular diseases like heart attack and stroke where platelets are known to play a significant role in the formation of fatty deposits in blood vessels (atherosclerosis). Platelet function is also heavily implicated in conditions like autoimmune thrombocytopenia where the body's immune system mistakenly attacks and destroys platelets, Gibbins says, highlighting one area of particular interest to the company.
Thrombotic adverse events experienced with the AstraZeneca COVID vaccine were platelet-mediated, continues Gibbins, making vaccine development another area likely to be important to HaemAnalytica. Platelets are also involved in cancer and metastasis, and “not just hematologic cancers but cancers generally.”
Overall, the company is interested in seeing platelets serve as biomarkers indicating whether someone is susceptible to a specific therapy, Gibbins says, as well as thrombosis and bleeding that can occur with some of the newer cancer drugs targeting enzymes. In terms of drug development overall, HaemAnalytica intends to help companies screen out problematic compounds that fail because they interfere with blood clotting.
The TRIPLE Score measures proteins on blood platelets signaling if an individual’s blood is more likely to form clots, together with that person’s age, Gibbins explains. Unlike measuring proteins on cells, measuring platelet function is harder to do and requires specialized equipment and expertise, which is where HaemAnalytica comes in.
Technicians or nurses working in a hospital setting can dispense patients’ blood into a standard well plate, put it in the freezer, and send it to the company for processing. Existing cardiovascular score systems—e.g., QRISK3 in the UK and ASCVD in the U.S.—will have already flagged individuals as being at heightened risk and the TRIPLE Score would indicate if they also had high platelet function, confirming that a blood thinner would be a good option.
The plan is to eventually develop TRIPLE Score into a point-of-care test. When tested out on a larger group of patients, this could help sort patients into risk categories.
The economics surrounding the test certainly looks good, says Gibbins. In the UK, it has been estimated that roughly 88,000 people die from a heart attack or stroke each year and a “reasonable proportion” of patients who get antiplatelet therapy experience bleeding, which in the brain and the stomach can be serious and expensive complications.
Treating those patients is costing the National Health Service “hundreds of millions of pounds” and it’s the same story in the U.S. where similarly large sums are being expended by Medicare, Gibbins says. And that doesn’t include the cost of lost productivity and the impact that those cardiovascular events have on society as well as care costs, which can be substantial. “A sizable proportion of individuals who have heart attacks in the UK are of the age where they should be economically active, and so this has a big impact on the economy generally.”
The potential savings would easily justify the cost of TRIPLE Score, which he estimates would be about £40 or £50 per test in the UK, or between $50 and $60 in the U.S.
Although HaemAnalytica just spun out of the University of Reading and will be based on campus for another few months, the company’s mainstay technology for precisely determining platelet function has been under development for more than two decades, says Gibbins. This is because the analysis of function is far more complicated than measuring biomarker levels in the blood.
“Platelets are designed to be triggered when they encounter things they shouldn’t normally see,” he explains. “When you cut yourself and blood starts to leak... the first thing platelets encounter is the tissue outside of the blood vessel... [along with] proteins and other factors that cause the platelets to become activated. It is important that the response happens quickly,” he adds, and multiple positive feedback pathways provide a failsafe mechanism for expediting that process.
It's one reason why thrombosis and heart attacks are so prevalent and can be catastrophic, adds Gibbins. “Platelets don’t know that they’re responding to disease rather than injury. These cells are so reactive that whenever you handle them and take them out of the blood or put them through machines, they can very easily become activated and... [then] they stick to each other and become unmanageable, and it becomes very difficult to measure their normal functions.”
Like other scientists around the world focused on platelet biology, Gibbins and his team have come up with a few “tricks” to get the cell fragments to behave. Working with them is “as much an art form as it is a science,” he quips. “We get fantastic quality data, but our assays are very simple.”
Much of the technology will eventually be accessible for any lab to use, Gibbins says. But for now, the tests are all being run in-house to ensure good diagnostic performance.
The HaemAnalytica team has started to expand some of its tests, most notably the TRIPLE Score, for use on a much larger scale, says Gibbins. Most of the other assays under development by the company are designed to help the pharmaceutical industry gauge the effectiveness of compounds under development rather than support treatment decision-making.
Cardiovascular disease affects a lot of people, and many medicines have been developed to treat them, he says. “We also now have the tools that will enable us to use those drugs more effectively in the future... [and] hopefully reduce the number of people who have to go through the misery of having a large infarct or stroke.”