Platelet function testing: Update on determinant variables and permissive windows using a platelet-count-based device.

While there are various aspects of platelet biology that can be studied in the lab (i.e. adhesion, degranulation, integrin activation), the master test for platelet function is that which gives a measure of the platelet aggregation capacity upon stimulation with an agonist. Platelet function testing is necessary for the diagnosis of platelet disorders and the monitoring of patients receiving anti-platelet treatments. Furthermore, it becomes relevant in the quality control of platelet concentrates for transfusion purposes, especially considering the global concern about long term storage, other forms of storage (i.e. cryopreservation, lyophilization), and the impact of Pathogen Reduction Treatments (PRTs) on platelet performance upon transfusion. However, it has been acknowledged as technically difficult and demanding, since a fine platelet function test must be carried out under specific conditions. Still, there might be occasions that preclude the platelet function testing abiding to the gold standard requirements, thus, leaving us with the necessity to redefine which variables may condition or limit the analysis of platelet function testing. In the present manuscript, we test different variables (such as the anticoagulant used or the time elapsed since extraction) and the possibility to reconstitute blood prior to platelet function analysis. This study aims to provide windows of action at the diagnostics lab, especially when not all of the recommended procedures and conditions can be followed: for example, when a sample is sent from a long distance, when there is a limitation on blood extraction volume or when certain parameters (platelet count) preclude reliable test results.

Proteomics-wise, how similar are mouse and human platelets?

The field of proteomics and its application to platelet biology, is rapidly and promisingly developing. Platelets (and megakaryocytes) are postulated as biosensors of health and disease, and their proteome poses as a tool to identify the specific health-disease hallmarks. Furthermore, the clinical management of certain pathologies where platelets are active players demands the development of alternative treatments, such is the case in patients where the balance thrombosis-bleeding is compromised, and a proteomics approach might aid at the identification of novel targets. Hereby, the mouse and human platelet proteomes and secretomes from public databases are compared, which shows that human and mouse platelets share a highly conserved proteome, considering identified proteins, and most importantly, their relative abundance. These supports, also interspecies wise, the use of the proteomics tool in the field, substantiated by a growing number of clinically relevant studies in humans or preclinical models. While the study of platelets through proteomics seems accessible and direct (i.e. noninvasive blood sampling, enucleated), there are some points of concern regarding the quality control of samples for such proteomics studies. Importantly, the quality of the generated data is improving over the years, which will allow cross-study comparisons. In parallel, the application of proteomics to the megakaryocyte compartment has a promising but long journey ahead. We foresee and encourage the application of platelet proteomics for diagnostic/prognostic purposes even beyond hematopoiesis and transfusion medicine, and as a tool that will procure the improvement of current therapies and the development of alternative treatment options.

The unbiased identification and quantitation of the protein profile (the so-called proteome) of cells, tissues, or organs, has gained attention from different fields because it gives additional valuable information to research questions. Understanding the protein building blocks of a biological system in normal physiological processes and how this may be altered in disease, may allow the discovery of biomarkers that could be used in diagnosis (early diagnosis), prognosis of disease or response to treatment. Furthermore, it may allow the identification of novel targets to develop personalized treatment options. Platelets, the anucleate cell components of the blood in charge of maintaining the body hemostasis, are postulated as biosensors of health and disease, and their proteome poses as a tool to identify health-disease hallmarks. Since platelets are in the circulation, a noninvasive blood sample is sufficient to obtain platelets from donors or patients in order to acquire information of the platelet proteome. Still, some research questions might require the use of animal preclinical models, where researchers may phenocopy human disorders, pathologies or diseases, to better understand the mechanisms behind these traits and to test potential novel treatments. How meaningful the studies in preclinical models are depends on how similar the biological systems of study are, interspecies wise. Hereby, the mouse and human platelet proteomes from available databases obtained by different research groups are compared, which shows that human and mouse platelets share a highly conserved proteome, considering identified proteins, and most importantly, their relative abundance. These supports, also interspecies wise, the use of the proteomics tool in the field, an approach with growing clinical relevance, as discussed.