Abstract
CD40 Ligand (CD40L) is expressed on platelets upon ADP stimulation and is involved in haemostasis. CD40L deficient mice exhibit thrombus instability and increased bleeding time. We investigated the relationships between plasma and platelet-associated CD40L, ADP signaling and bleeding event occurrence in patients receiving thienopyridines one month after a stented Acute Coronary Syndrome (ACS). Basal platelet CD40L surface expression (pCD40L), pCD40L after PAR-1 agonist stimulation (TRAP pCD40L) and platelet released CD40L (rCD40L) were quantified. Results were compared to VASP as a measure of P2Y12 inhibition level. We included 318 patients between November 2012 and June 2014. Thienopyridines treated patients exhibit low pCD40L, TRAP pCD40L and rCD40L in comparison with controls. pCD40L and rCD40L were correlated with PRI-VASP. Thienopyridine treatment strongly reduces rCD40L. Hyperesponder to thienopyridine status is associated with high levels of TRAP pCD40L. pCD40L and TRAP pCD40L levels are reduced in the bleeding cohort. In multivariate analysis pCD40L significantly contributes to bleeding risk independently of PRI-VASP. pCD40L and rCD40L levels are reduced by thienopyridines. pCD40L associates with the bleeding risk independently of the VASP levels and may represent a novel target to assess bleeding risk in thienopyridine-treated ACS patients.
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