Abstract 12904: Ticagrelor Removal From Human Blood

Abstract

Background: In acute coronary events, ticagrelor is recommended to be loaded prior to cardiac catheterization. In the PLATO study the rate of severe bleeding on ticagrelor in patients who needed urgent bypass graft surgery was high but similar for ticagrelor and clopidogrel. The reversible binding mode of action of ticagrelor onto the P2Y12 receptor provides an opportunity for drug removal not possible for the thienopyridines (clopidogrel and prasugrel) which are all irreversibly binding to P2Y12. Objective: Our goal was to devise an efficient method for ticagrelor removal from blood. Methods: Ticagrelor removal was measured in two sets of experiments. The first set was performed in a first-pass manner and used as drug vehicle bovine serum albumin (BSA) solution (0.4% and 4%), while the second set employed in three experiments blood either bought from BioreclamationIVT (older than 24 hours) or freshly collected from a healthy volunteer and mixed with ticagrelor at a concentration of approximately 5.1 ug/mL. BSA solution as well as blood carrying ticagrelor were passed at various velocities through columns containing two types of sorbent (Cytosorb and Porapak Q). Ticagrelor concentration was measured from the affluent and effluent solution using a liquid chromatography technique with tandem mass spectrometric detection LC/MS/MS). Results: Ticagrelor removal peaked at 99% and 100% using 40 mL Cytsorb and Porapak Q columns, respectively, during BSA experiments. The most efficient ticagrelor drug removal from blood was obtained with 260 mL sorbent (113 g of Cytosorb), with a peak removal from whole blood of 100% and 99% from blood cells during a 10-hour recirculating experiment reaching blood and plasma levels of 15 and 2 ng/mL, respectively, much below the ticagrelor platelet aggregation inhibition IC50 levels (30 ng/mL). Cytosorb has been also shown to absorb in bench experiments 99% of dabigatran in albumin solution and up to 96% of radiocontrast, creating the premises of a possible all-inclusive method of antiplatelets, anticoagulants, and radiocontrast removal. Conclusion: Sorbent adsorption demonstrates robust removal of ticagrelor from BSA solution and human blood samples.