Increased Plasma Concentrations of Soluble CD40 Ligand in Acute Coronary Syndrome Depend on in Vitro Platelet Activation (Hemostasis and Trombosis‪)‬

CD40 ligand (CD40L [4]; CD154) is a homotrimeric type II transmembrane protein. Its C-terminus contains a tumor necrosis factor homology domain required for binding to its receptor CD40. Intracellular CD40L is expressed on platelet membranes in response to platelet activation (1). Subsequent cleavage by metalloproteases produces soluble CD40L (sCD40L), an 18-kDa soluble fragment (2). Many reports have suggested that sCD40L is a promising clinical biomarker of atherothrombotic risk. Increased concentrations of sCD40L were reported mostly in disorders associated with platelet activation such as acute and stable coronary artery disease (3-5). Coronary artery bypass graft surgery and percutaneous coronary intervention (PCI) were shown to increase sCD40L (3,6). Conversely, increased sCD40L was also directly associated with a higher cardiovascular risk in patients undergoing PCI (7). In spite of the great interest in this biomarker, sCD40L still awaits appropriate clinical validation (8). Although preanalytical conditions may influence sCD40L concentrations significantly, they have not been standardized for the measurement of this marker (9-13). This lack of standardization prompted us to examine the effects of preanalytical conditions on the measurement of sCD40L in samples collected from healthy control individuals and patients with acute coronary syndrome (ACS) and sepsis--both diseases are associated with in vivo platelet activation. Platelet activation was independently determined by measurement of [beta]-thromboglobulin ([beta]TG) and platelet factor 4 (PF4) concentrations. In response to activation, these proteins are rapidly secreted from platelet granules in a constant molar ratio. Decrease of the [beta]TG:PF4 ratio is a sensitive indicator of in vitro platelet activation (14).