Platelet Reactivity Signature in Scattergrams Shows Genetic Predictors of Thrombotic Disease

Platelet reactivity can be predicted from complete blood count scattergrams generated by widely used hematology analyzers, according to a report in the journal Blood. Researchers used the method to investigate genetic determinants of platelet reactivity and causal associations with thrombotic disease.

“Our genome-wide association study of predicted plate reactivity in 29,806 blood donors was able to identify variants known to be associated with plate reactivity to various agonists, without the need for technically challenging platelet stimulation experiments, by exploiting previously unrecognized information on plate reactivity contained in Sysmex XN scattergrams derived from EDTA-treated whole blood,” wrote first author Hippolyte Verdier of Institut Pasteur, Paris, France, and coauthors.

The study found 21 distinct associations implicating 20 genes with variants, 6 of which were identified in previous genome-wide association studies. A genetic score for platelet reactivity that reflected the 21 variants was associated with myocardial infarction and pulmonary embolism incidence rates, according to the study.

In Mendelian randomization analyses, platelet reactivity was causally associated with the risk of coronary artery disease, stroke, and venous thromboembolism, researchers reported.

“These results represent the first time the causality of platelet reactivity as a risk factor for cardiovascular events has been demonstrated using genome-wide instrumental analyses,” they wrote. “Other difficult-to-measure risk factors with correlates that are easy to measure may benefit from a similar approach.”

In an accompanying commentary, Paul S. de Vries, PhD, of the University of Texas Health Science Center at Houston, noted the importance of platelet function in the 3 thrombotic diseases per the Mendelian randomization analyses findings.

“The association with coronary artery disease is notable because the vast majority of identified genetic associations appear to be driven by atherosclerotic plaque development and not by the thrombotic response to plaque rupture,” Dr de Vries wrote.

“Although the insights gleaned from the first application of this approach are impressive in their own right,” he continued, “the true promise of this approach lies in future applications on even larger data sets, which would expand our understanding of the genetic architecture of platelet reactivity and potentially lead to the discovery of novel drug targets.”

References

Verdier H, Thomas P, Batista J, et al. A signature of platelet reactivity in CBC scattergrams reveals genetic predictors of thrombotic disease risk. Blood. 2023;142(22):1895-1908. doi:10.1182/blood.2023021100

de Vries PS. Genetics of predicted platelet reactivity. Blood. 2023;142(22):1851-1852. doi:10.1182/blood.2023022302