People at risk from strokes and heart attacks could benefit from personalized clotting profiles to help clinicians prescribe more precise treatments, according to a report (“Multiparameter phenotyping of platelet reactivity for stratification of human cohorts”) published in Blood Advances. Researchers created a test that separates people into different groups based on how their bodies respond to clotting events.

The team from the University of Reading and University of Cambridge used samples of donated blood from human participants, treated them in a laboratory to find out how platelets in their blood responded to a range of stimulants to trigger blood clotting, and developed new computer software and algorithms to analyze and classify the data.

“Accurate and comprehensive assessment of platelet function across cohorts of donors may be key to understanding the risk of thrombotic events associated with cardiovascular disease, and, hence, to help personalize the application of antiplatelet drugs. However, platelet function tests can be difficult to perform and analyze; they also can be unreliable or uninformative and poorly standardized across studies,” write the investigators.

“The Platelet Phenomic Analysis (PPAnalysis) assay and associated open-source software platform were developed in response to these challenges. PPAnalysis utilizes preprepared freeze-dried microtiter plates to provide a detailed characterization of platelet function. The automated analysis of the high-dimensional data enables the identification of subpopulations of donors with distinct platelet function phenotypes.

“Using this approach, we identified that the sensitivity of a donor’s platelets to an agonist and their capacity to generate a functional response are distinct independent metrics of platelet reactivity. Hierarchical clustering of these metrics identified 6 subgroups with distinct platelet phenotypes within healthy cohorts, indicating that platelet reactivity does not fit into the traditional simple categories of “high” and “low” responders. These platelet phenotypes were found to exist in 2 independent cohorts of healthy donors and were stable on recall.

“PPAnalysis is a powerful tool for stratification of cohorts on the basis of platelet reactivity that will enable investigation of the causes and consequences of differences in platelet function and drive progress toward precision medicine.”

“This research showcases how we can better understand the individual ways that our platelets respond to events that lead to clotting, either when clotting is needed for healing, or when they shouldn’t, which is when strokes and heart attacks happen,” says Joanne Dunster, PhD, a mathematician based in the Institute for Cardiovascular and Metabolic Research at the University of Reading.

Two important and interdependent characteristics

The scientists found that there were two important and independent characteristics that the platelets displayed, the sensitivity of a response to an agent, and the strength of response. These were found to be independent characteristics and allowed donors to be classified into different groups.

As a result of the testing, the research team were able to group donors into six distinct groups which remained the same for the majority of samples after retesting two years later.

“The next big thing in medicine is the idea of personalization of treatments, which requires much more detailed profiles of our bodies. Heart disease and strokes are the biggest killers around the world, and millions of patients are prescribed drugs to reduce their risk of having a potentially deadly attack,” notes Jon Gibbins, PhD, director of the Institute of Cardiovascular and Metabolic Research at the University of Reading.

“Currently mostly patients are treated the same–a one size fits all approach.  We hope that our new testing will allow us to predict who needs treatment and which drug to use.

“This new research is therefore really exciting as we have a framework for building a personalized clotting profile that is simple to administer and could help clinicians to prescribe more effective treatments to reduce the risks of strokes and heart disease further.”

The researchers are now examining the use of the test with patients with established heart disease to help pave the way to personalized medicine approaches.

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