Abstract: Objective This study aimed to assess the association of clinical factors with P2Y 12 -dependent platelet inhibition as monitored by the ratio of ADP- to TRAP-induced platelet aggregation and conventional ADP-induced aggregation, respectively. BackgroundControversial findings to identify and overcome high platelet reactivity (HPR) after coronarystent-implantation and to improve clinical outcome by tailored anti-platelet therapy exist. Monitoring anti-platelet therapy ex vivo underlies several confounding parameters causing that ex vivo platelet aggregation might not reflect in vivoplatelet inhibition.MethodsIn a single centre observational study, multiple electrode aggregometry was performed in whole blood of patients after recent coronary stent-implantation. Relative ADP-induced aggregation (r-ADP-agg) was defined as the ratio of ADP- to TRAP- induced aggregation reflecting the individual degree of P2Y 12-mediated platelet reactivity. ResultsPlatelet aggregation was assessed in 359 patients. Means (±SD) of TRAP-, ADP-induced aggregation and r-ADP-agg were 794±239 AU*min, 297±153 AU*min and 37±14%,respectively. While ADP- and TRAP-induced platelet aggregation correlated significantly with platelet count (ADP: r = 0.302; p

Abstract: Integrin-based therapeutics have garnered considerable interest in the medical treatment of inflammation. Integrins mediate the fast recruitment of monocytes and neutrophils to the site of inflammation, but are also required for host defense, limiting their therapeutic use. Here, we report a novel monoclonal antibody, anti-M7, that specifically blocks the interaction of the integrin Mac-1 with its pro-inflammatory ligand CD40L, while not interfering with alternative ligands. Anti-M7 selectively reduces leukocyte recruitment in vitro and in vivo. In contrast, conventional anti-Mac-1 therapy is not specific and blocks a broad repertoire of integrin functionality, inhibits phagocytosis, promotes apoptosis, and fuels a cytokine storm in vivo. Whereas conventional anti-integrin therapy potentiates bacterial sepsis, bacteremia, and mortality, a ligand-specific intervention with anti-M7 is protective. These findings deepen our understanding of ligand-specific integrin functions and open a path for a new field of ligand-targeted anti-integrin therapy to prevent inflammatory conditions