ABSTRACT
Platelet aggregation is a complicated process mediated by different signaling pathways. As the process is highly complex and apparently redundant, the relationships between these pathways are not yet fully known. The aim of this project was to study the interconnections among seven different aggregation pathways in a group of 53 generally healthy volunteers aged 20 to 66 years. Platelet aggregation was induced with thrombin receptor activating peptide 6 (TRAP), arachidonic acid (AA), platelet activating factor 16 (PAF), ADP, collagen, thromboxane A2 analogue U46619 or ristocetin (platelet agglutination) ex vivo in fasting blood samples according to standardized timetable protocol. Additionally, some samples were pre-treated with known clinically used antiplatelet drugs (vorapaxar, ticagrelor or acetylsalicylic acid (ASA)). Significant correlations among all used inducers were detected (Pearson correlation coefficients (rP): 0.3 to 0.85). Of all the triggers, AA showed to be the best predictor of the response to other inducers with rP ranging from 0.66 to 0.85. Interestingly, the antiplatelet response to ticagrelor strongly predicted the response to unrelated drug vorapaxar (rP = 0.71). Our results indicate that a response to one inducer can predict the response for other triggers or even to an antiplatelet drug. These data are useful for future testing but should be also confirmed in patients.
What is the context?⢠Platelet activation is a complicated process with multiple signaling cascades involved.⢠A total of seven common platelet triggers (ADP, collagen, TRAP-6, PAF, arachidonic acid/AA/, ristocetin and U46619) were tested.⢠The process is dependent on many factors including sex, age, concomitant disease(s), pharmacotherapy.What is new?⢠There were significant correlations between all tested aggregatory cascades.⢠AA has the highest rate of response predictability in our heterogeneous generally healthy volunteer group.⢠There was no correlation between impedance aggregometry in whole blood and turbidimetric measurement with platelet-rich plasma.What is the impact?⢠The effect of antiplatelet drugs can be assessed from the reaction to different trigger(s) at least in this group of healthy patients.⢠Future studies must test these relationships in patients with different diseases.
