Introduction to a review series on platelet heterogeneity Free

Long recognized for their role in hemostasis and thrombosis, platelets are now known to be important in other areas including sepsis, cancer, vascular integrity, and inflammation. Key to this versatility has been the discovery that not all platelets may be alike, with differences in age, activation status, granular content, receptor status, size, and location of origin, all enabling platelets to multitask. In addition to their naïve state, platelets also experience a chameleon effect, with additional modifications dictated by exposure to systemic disease, making them dynamic within circulation. Recognizing this novelty, platelets are poised as integral players in precision medicine as potential biomarkers of disease and future tailored therapeutics.

This review series includes the following articles:

• Rainer Kaiser, Afra Anjum, and Leo Nicolai, “Platelet heterogeneity in disease: the many and the diverse?”

• Michael W. Malloy, Kathleen E. McGrath, and Craig N. Morrell, “Platelet heterogeneity: variety makes immune and vascular function better”

• Thomas Thiele, Johan W. M. Heemskerk, and Andrew L. Frelinger III, “Clinical and research methods for analysis and study of platelet populations”

In the review by Kaiser et al, the authors define the different characteristics that can differentiate platelet subpopulations, highlighting the heterogeneity in age, origin, and circulatory disease modification. Next the authors discuss the role of these subsets in disease progression and in turn how platelet subtypes are further modified by disease states. Lastly, they share how defining platelet subpopulations represents an untapped area for risk stratification and precision medicine.

Malloy et al further define platelet subpopulations in disease describing their functionality in vascular repair, immune mediation, infection, and angiogenesis. In addition, they take us back to platelet origin, focusing on subpopulations of their precursor cell, the megakaryocyte, describing how location dictates their characteristics, ultimately contributing to platelet heterogeneity. Their review focuses not only on the role of platelet subpopulations in disease causality but also on the maintenance of health.

Providing a methodology for classification and identification, Thiele et al define laboratory and clinical methods of identifying platelet subpopulations. Recognizing differences in classification, they also address technical issues in platelet subpopulation identification. This focus on diagnostics provides a path toward clinical integration of platelet subtyping taking us a step forward in the direction of targeted medicine for platelet-mediated disease.

Acknowledging that the concept of platelet heterogeneity is not without controversy, the authors in this review series address areas of debate in the context of platelet subpopulations. Calling into question the existence of distinct platelet subtypes in opposition to a continuum of functionality, the reviews address areas of overlap including platelet activation and aging. Evaluating the classification of distinct platelet groups, the differences in the markers used to identify these populations are also raised. Lastly, taking the heterogeneity back to its origin, the topic of megakaryocyte subpopulations as a source of platelet heterogeneity is also raised.

This review series provides a comprehensive update on an emerging topic in the field of platelet biology reviewing platelet heterogeneity with implications for diagnostics, functionality, and disease. Recognizing the limitations in this area, these studies are the foundation for incorporating platelet subtyping into clinical decision-making and more precisely targeted platelet therapeutics.