Reversibility of platelet P2Y12 inhibition by platelet supplementation: ex vivo and in vitro comparisons of prasugrel, clopidogrel and ticagrelor

J Thromb Haemost. 2018 Jun;16(6):1089-1098. doi: 10.1111/jth.14014. Epub 2018 Apr 23.


Essentials Successful outcome of platelet transfusion depends on specific antiplatelet therapy in use. We assessed if ticagrelor, clopidogrel or prasugrel impacts on donor platelet activity ex vivo. Ticagrelor and/or its active metabolite in plasma or bound to platelets can inhibit donor platelets. This might compromise the effectiveness of platelet transfusion therapy.

Summary: Background Platelet transfusion is the conventional approach to restore platelet function during acute bleeds or surgery, but successful outcome depends on the specific antiplatelet therapy. Notably ticagrelor is associated with inadequate recovery of platelet function after platelet transfusion. We examined whether plasma and/or platelets from ticagrelor-treated patients influence donor platelet function, in comparison with clopidogrel and prasugrel. Methods Platelet transfusion was mimicked ex vivo by mixing naïve donor platelet-rich plasma (PRP) or gel-filtered platelets (GFP) in defined proportions with PRP, plasma or GFP from cardiovascular patients receiving standard care including medication with prasugrel, clopidogrel or ticagrelor (n = 20 each). Blood was taken 4 h after the previous dose. HLA2/HLA28 haplotyping let us distinguish net (all platelet) and individual patient/donor platelet reactivity in mixtures of patient/donor platelets, measured by flow cytometry analysis of ADP-induced fibrinogen binding and CD62P expression. Results ADP responsiveness of donor platelets was dramatically reduced by even low (10%) concentrations of PRP or plasma from ticagrelor-treated patients. Clopidogrel and prasugrel were associated with more modest donor platelet inhibition. GFP from ticagrelor-treated patients but not patients receiving clopidogrel or prasugrel also suppressed donor GFP function upon mixing, suggesting the transfer of ticagrelor from patient platelets to donor platelets. This transfer did not lead to recovery of ADP responsiveness of patient's platelets. Conclusion Collectively, these observations support the concept that ticagrelor and/or its active metabolite in plasma or bound to platelets can inhibit donor platelets, which might compromise the effectiveness of platelet transfusion therapy.

Keywords: ADP; P2Y12 antagonist; platelet; reversibility; thienopyridine.

Publication types

  • Comparative Study

MeSH terms

  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Clinical Decision-Making
  • Clopidogrel / adverse effects
  • Clopidogrel / therapeutic use*
  • Female
  • Humans
  • Male
  • Patient Selection
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Function Tests
  • Platelet Transfusion* / adverse effects
  • Platelet-Rich Plasma / drug effects*
  • Prasugrel Hydrochloride / adverse effects
  • Prasugrel Hydrochloride / therapeutic use*
  • Purinergic P2Y Receptor Antagonists / adverse effects
  • Purinergic P2Y Receptor Antagonists / therapeutic use*
  • Receptors, Purinergic P2Y12 / blood
  • Receptors, Purinergic P2Y12 / drug effects*
  • Risk Factors
  • Ticagrelor / adverse effects
  • Ticagrelor / therapeutic use*


  • P2RY12 protein, human
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Receptors, Purinergic P2Y12
  • Clopidogrel
  • Prasugrel Hydrochloride
  • Ticagrelor