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.

Hemato-oncological patients with chemotherapy-induced thrombocytopenia are a major recipient group of frequent platelet (PLT) transfusion. Prophylactic platelet transfusions are administered when platelet counts fall below 10 × 10⁹ PLT/L, to prevent severe or fatal bleeding. However, these prophylactic platelet transfusions do not always result in the prevention of bleeding. Pre- or post-transfusion acquired dysfunction of donor platelets in this respect could play a role. We previously reported intrinsic and transfusion-dependent platelet alterations in hemato-oncological patients. In particular, the expression of relevant platelet receptors was affected in donor platelets after incubation with patient’s plasma, which could explain, at least in part, the variable efficacy of platelet transfusions in these patients. In the present manuscript we show that plasma from acute myeloid leukemia (AML) patients undergoing chemotherapy inhibits functionality of allogenic platelets. Further proteomic analysis allowed us to observe alterations in the composition of plasma samples, and to identify key plasma components which could be responsible for platelet function inhibition and explain bleeding in patients notwithstanding platelet transfusions. We anticipate that with the obtained results, platelet transfusion support can be further personalized in patients receiving chemotherapy and applications might expand to maximize the clinical efficacy of procedures such as bone marrow transplantation.