Antagonizing P2Y 12 Receptor Inhibitors: Current and Future Options

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Abstract

There are clinical scenarios where the balance between the risk of ischemic and bleeding events leads to the clinical decision to reverse the antiplatelet effect of P2Y 12 receptor inhibitors. These scenarios comprise emergency situations such as active severe bleeding, urgent procedures with presumed high bleeding risk, or major trauma with (anticipated) bleeding. Supplementation of platelets has been investigated in ex vivo as well as in in vivo studies. These studies indicate that the inhibition of adenosine diphosphate-induced aggregation by the irreversibly binding thienopyridine derivatives clopidogrel and prasugrel can be reversed by administration of platelet concentrates. Supplementation of platelets in patients on prasugrel is more effective if this can be transfused > 6 hours after last dosing. Studies on the reversal effect obtained by administration of platelet concentrates in patients on ticagrelor show conflicting results. Experimental data suggest that administration of serum albumin might increase the reversal effect. A monoclonal antibody fragment (PB2452) for neutralizing ticagrelor is currently in clinical development. A recently published first in man study shows that reversal of platelet inhibition occurs within 5 minutes after start of administration and the effect is maintained for 20 to 24 hours after a 16-hour infusion which is by far the most effective approach for reversal of ticagrelor.

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Trenk, D., Hille, L., Leggewie, S., Stratz, C., Nührenberg, T. G., Aradi, D., … Sibbing, D. (2019). Antagonizing P2Y 12 Receptor Inhibitors: Current and Future Options. Thrombosis and Haemostasis, 19(10), 1606–1616. https://doi.org/10.1055/s-0039-1693738

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