Circulating monocyte-platelet aggregates are a more sensitive marker of invivo platelet activation than platelet surface P-selectin - Studies in baboons, human coronary intervention, and human acute myocardial infarction

Background-Platelet surface P-selectin is considered the "gold standard" ma rker of platelet activation. Degranulated, P-selectin-positive platelets, h owever, aggregate with leukocytes in vitro and rapidly lose surface P-selec tin in vivo. Methods and Results-Flow cytometric tracking of autologous, biotinylated pl atelets in baboons enabled us to directly demonstrate for the first time in vivo that (1) infused degranulated platelets very rapidly form circulating aggregates with monocytes and neutrophils, and (2) 30 minutes after infusi on of the degranulated platelets, the percentage of circulating monocytes a ggregated with infused platelets persist at high levels, whereas the percen tage of circulating neutrophils aggregated with infused platelets and the p latelet surface P-selectin of nonaggregated infused platelets return to bas eline. We therefore performed 2 clinical studies in patients with acute cor onary syndromes. First, after percutaneous coronary intervention (n=10), th ere was an increased number of circulating monocyte-platelet (and to a less er extent, neutrophil-platelet) aggregates but not P-selectin-positive plat elets. Second, of 93 patients presenting to an Emergency Department with ch est pain, patients with acute myocardial infarction (AMI) (n=9) had more ci rculating monocyte-platelet aggregates (34.2 +/- 10.3% [mean +/- SEM]) than patients with no AMI (n=84, 19.3 +/-1.4%, P <0.05) and normal control subj ects (n=10, 11.5 +/-0.8%, P <0.001). Circulating P-selectin-positive platel ets, however, were not increased in chest pain patients with or without AML Conclusions-As demonstrated by 3 independent means (in vivo tracking of act ivated platelets in baboons, human coronary intervention, and human AMI), c irculating monocyte-platelet aggregates are a more sensitive marker of in v ivo platelet activation than platelet surface P-selectin.