Figure 5: Inhibition of ADP-Induced Platelet Aggregation With Cangrelor

(A to D) Representative tracings of adenosine diphosphate (ADP) (20 μM)-induced aggregation of platelets isolated from neonatal and pediatric patients with congenital heart disease or healthy adult volunteers in the presence of indicated concentrations of cangrelor. (E to H) Concentration response curves for determination of IC50 values (the concentration of an inhibitor where the response [or binding] is reduced by one-half) for cangrelor (20-μM ADP) as measured by light transmission aggregometry. Concentrations of cangrelor are plotted in log form, and all data were normalized to aggregation in the absence of drug. n = 12 (age 0 to 28 days); n = 7 (age 1 to 10 years); n = 7 (age 11 to 18 years); n = 12 for adults. (I) Representative tracing of fluorescently labeled platelet accumulation on surface-immobilized collagen using whole blood from neonates with single-ventricle physiology and a multi-well microfluidic flow device (n = 5; 40 separate clotting events at 100 s1). Insert shows platelet deposition at t = 300 s in the absence or presence of cangrelor (11.6 nM). (J) Mean platelet fluorescence intensities at t = 300 s after the addition of cangrelor to whole blood collected from the patients described in I. Data represent mean ± SEM. ***p < 0.001 for drug versus no treatment according to the Mann-Whitney U test. PFI = platelet fluorescence intensity.