Platelets are protective guardians of the vasculature during stress and injury as well as regulators in inflammation and immune responses. Despite their small size and anucleate status, platelets contain a repertoire of RNAs and unspliced pre-mRNA that can be processed into mRNA and functional proteins. Platelet transcriptomics has been applied to understand genetically or environmentally induced alterations in platelet function. Further the platelet transcriptome is conserved between humans and genetic model organism. Platelets carry miRNAs that may be regulate cellular functions of nucleated cells. While racially determined variations in platelet transcript profiles show correlation with prothrombotic platelet responses, it is incompletely understood how platelets are phenotypically changed when chronically exposed to a prothrombotic environment. We recently demonstrated in a prothrombotic mouse model that platelets display a marked hyperreactivity in response to intravascular prothrombotic challenges and higher surface expression of phosphatidylserine (PS), consistent with chronic activation. We will further study this mouse model and analyze the platelet function, platelet transcriptome, and proteomic analysis jointly with the CTH cooperating partners. These studies will provide new insights into changes resulting from a chronic exposure of platelets or their precursors to thrombin and yield potential new biomarkers for prothrombotic states to be evaluated clinically in collaboration with the project ‘Platelet and leukocyte dysfunction in essential thrombocythemia (ET)’. In the long term, we will pursue studies on the utility of these markers as predictors for prothrombotic complications in myeloproliferative disorders.