Soluble Platelet Release Factors as Biomarkers for Cardiovascular Disease

Abstract

Platelets are the main players in thrombotic diseases, where activated platelets not only mediate thrombus formation but also are involved in multiple interactions with vascular cells, inflammatory components, and the coagulation system. Although in vitro reactivity of platelets provides information on the function of circulating platelets, it is not a full reflection of the in vivo activation state, which may be relevant for thrombotic risk assessment in various disease conditions. Therefore, studying release markers of activated platelets in plasma is of interest. While this type of study has been done for decades, there are several new discoveries that highlight the need for a critical assessment of the available tests and indications for platelet release products. First, new insights have shown that platelets are not only prominent players in arterial vascular disease, but also in venous thromboembolism and atrial fibrillation. Second, knowledge of the platelet proteome has dramatically expanded over the past years, which contributed to an increasing array of tests for proteins released and shed from platelets upon activation. Identification of changes in the level of plasma biomarkers associated with upcoming thromboembolic events allows timely and individualized adjustment of the treatment strategy to prevent disease aggravation. Therefore, biomarkers of platelet activation may become a valuable instrument for acute event prognosis. In this narrative review based on a systematic search of the literature, we summarize the process of platelet activation and release products, discuss the clinical context in which platelet release products have been measured as well as the potential clinical relevance.

Anti‐severe acute respiratory syndrome coronavirus‐2 adenoviral‐vector vaccines trigger subclinical antiplatelet autoimmunity and increase of soluble platelet activation markers

“…Third, we did not measure direct activation markers on circulating blood platelets. However, both EVs CD41 + and sP‐sel are established markers of in vivo platelet activation 54–56 …”

“…However, both EVs CD41 + and sP-sel are established markers of in vivo platelet activation. [54][55][56] Strenghts of our study are that it was performed after vaccine first doses, and several data suggest that VITT is limited to first-dose adenoviral-vector vaccines. 3,9 Moreover, we applied the false discovery rate with two-stage step-up correction as a statistical approach to avoid that random events could falsely appear significant, given the multiple hypotheses simultaneously tested.…”

A guide to molecular and functional investigations of platelets to bridge basic and clinical sciences

“…Immunodetection methods use specific antibodies and allow easy validation and a relatively inexpensive platform to identify proteins and detect quantitative differences. Enzymelinked immunosorbent assays (ELISA) have been regularly used for the measurement of soluble platelet-activation markers including soluble P-selectin and platelet factor 4 as well as the platelet secretome (from α-granules and dense granules) and the platelet sheddome (GPIbα, GPVI and other membrane proteins) [97][98][99] . Changes in the levels of plasma platelet-activation markers have been associated with thromboembolic events and form a valuable tool for acute event prognosis and timely individualized adjustment of the treatment regimen to prevent thrombosis.…”

Where the Action Is—Leukocyte Recruitment in Atherosclerosis

“…As a consequence, leukocyte integrins undergo conformational changes that result in increased binding to respective endothelial adhesion molecules ( 54 ). Of note, also soluble selectins, known biomarkers for inflammation ( 55 , 56 ), can induce integrin activation ( 57 ). Slow rolling can be viewed as a specific type of integrin-mediated rolling: It is induced by pro-inflammatory cytokine exposure, and mediated mainly by the subsequent upregulation of endothelial E-selectin which induces integrin activation ( 10 , 58 ).…”