Novel Test Could Personalize Blood Clot-Disorder Treatment

Human blood cells, SEM
Human blood cells. Coloured scanning electron micrograph (SEM) of normal human blood. The majority of the cells are red blood cells, but white blood cells (yellow) and platelets (pink) are also seen. Magnification: x1350 when printed at 10 centimetres wide. [Source: Science Photo Library —STEVE GSCHMEISSNER/Getty Images]

People at risk from strokes and heart attacks could benefit from personalized clotting profiles to help clinicians prescribe more precise treatments, thanks to new research from the University of Reading and University of Cambridge in UK. The Platelet Phenomic Analysis (PPAnalysis) assay they developed uses preprepared freeze-dried microtiter plates to provide a detailed characterization of platelet function.

In a paper published in Blood Advances, the researchers describe the test, which separates people into different groups based on how their bodies respond to clotting events.

The team used samples of donated blood from human participants and then treated them to find out how platelets responded to a range of stimulants that trigger blood clotting. They also developed new computer software and algorithms to analyze and classify the data.

Joanne Dunster, Ph.D., a mathematician based in the Institute for Cardiovascular and Metabolic Research at the University of Reading said, “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.”

Platelet function tests, the researchers note, can be difficult to perform and analyze. They also can be unreliable or uninformative and poorly standardized across studies. The PPAnalysis assay, and associated open-source software platform, were developed in response to these challenges.

The automated analysis of the high-dimensional data obtained from the assay allows identification of subpopulations of donors with distinct platelet function phenotypes. Using this approach, the researchers determined 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 six subgroups with distinct platelet phenotypes within healthy cohorts. These findings suggest platelet reactivity does not fit into the traditional simple categories of “high” and “low” responders. The team found the platelet phenotypes in two independent cohorts of healthy donors and they were stable on repeat testing over two years.

The two important and independent characteristics that the platelets displayed were 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.

Professor Jon Gibbins, director of the Institute of Cardiovascular and Metabolic Research at the University of Reading, said, “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. 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.”

He added: “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 team 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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