platelet activation, and were shown to be elevated in several pathophysiological circumstances, including myocardial infarction. On the other hand, activated GPIIb/IIIa interacts with plasma coagulation and facilitates platelet-platelet interactions. In our study, we assessed P-selectin expression, activated GPIIb/IIIa and MPA formation without the addition of platelet agonists. Since clopidogrel and prasugrel affect mainly adenosine diphosphate inducible platelet activation, these parameters should be independent of the type of ADP receptor antagonist. Therefore, we decided to include patients on clopidogrel as well as patients on prasugrel therapy. Indeed, P-selectin expression, activated GPIIb/IIIa and MPA formation did not differ significantly between clopidogrel- and prasugrel- 6 / 11 IL-6 and ADMA Are Associated with Platelet Activation Fig 1. Platelet surface expression of P-selectin and activated glycoprotein IIb/IIIa. Platelet surface expression of P-selectin in patients with high vs. low interleukin -6 levels. Platelet surface expression of 
activated GPIIb/IIIa in patients with high vs. low asymmetric dimethylarginine levels. The boundaries of the box show the lower and upper quartile of data, the line inside the box represents the median. Whiskers are drawn from the edge of the box to the highest and lowest values that are outside the box but within 1.5 times PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19768259 the box length. MFI, mean fluorescence intensity. doi:10.1371/journal.pone.0122586.g001 treated patients. Nevertheless, we performed an PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19769124 additional analysis including only clopidogreltreated patients. However, this did not change the results. Previous studies reported a worse response to antiplatelet therapy with aspirin and clopidogrel in patients with increased markers of inflammation. In detail, IL-6 was found to be an 7 / 11 IL-6 and ADMA Are Associated with Platelet Activation doi:10.1371/journal.pone.0122586.t003 independent predictor of on-treatment residual platelet reactivity in response to PR 619 supplier arachidonic acid by light transmission aggregometry and of urinary 11-dehydro-thromboxane B2 levels. Moreover, hsCRP levels were independent predictors of platelet reactivity when determined by LTA, D-TXB2, the Impact-R and serum thromboxane B2. Other studies identified IL-6, CRP, WBC and RANTES as independent predictors of on-treatment platelet reactivity to AA and adenosine diphosphate by multiple electrode platelet aggregometry. However, all of these studies assessed only agonists’-inducible platelet reactivity. Consequently, data on the association between inflammation and in vivo platelet activation were missing, so far. Our findings suggest that the poor response to antiplatelet therapy in patients with increased inflammatory markers may at least in part derive from increased platelet activation in vivo. In a previous publication, supramedian IL-6 levels were independently associated with significantly higher levels of arachidonic acid-inducible platelet reactivity in patients undergoing angioplasty and stenting. Therefore, we decided to use the median as cut-off value for high IL-6 levels. In our study, only IL-6 was independently associated with both parameters of platelet activation and MPA formation. Other markers of inflammation, i.e. hsCRP and WBC, were not linked to P-selectin expression, activated GPIIb/IIIa and MPA formation. This finding suggests that IL-6 itself may contribute to platelet activation and leukocyte-platelet interaction in atherosclerotic cardiov