The effectiveness of platelet supplementation for the reversal of ticagrelor-induced inhibition of platelet aggregation: An in-vitro study

Eur J Anaesthesiol. 2016 May;33(5):361-7. doi: 10.1097/EJA.0000000000000348.

Abstract

Background: Management of ticagrelor-induced bleeding is challenging, as no antidote is currently available. Platelet transfusion, usually proposed to reverse antiplatelet drugs, has been suggested to be ineffective but few data are available.

Objective: To assess the efficacy of platelet supplementation to restore platelet aggregation inhibited by ticagrelor.

Design: In vitro study.

Setting: Blood samples were obtained from the French Blood Bank Institute.

Participants: Healthy blood donors.

Interventions: Whole blood from healthy donors was spiked with ticagrelor or aspirin (used as a positive control).

Main outcome measures: Platelet aggregation was investigated with impedance aggregometry on whole blood [expressed in ohms (V)] and light transmission aggregometry (expressed in %) on platelet-rich plasma using ADP or arachidonic acid as agonists for ticagrelor or aspirin, respectively. Platelet supplementation was defined as the addition of washed platelet suspension increasing at least 60% of whole blood platelet count.

Results: Ticagrelor (3.25 mM) inhibited ADP-induced platelet aggregation compared with control either in whole blood (2 vs. 13 V, P < 0.05) or in platelet-rich plasma (15 vs. 75% P < 0.05). Aspirin (25 mM) inhibited arachidonic acid-induced aggregation (1 vs. 7.5 V, P < 0.05 in whole blood and 5 vs. 77.5%, P = 0.01 in platelet-rich plasma). Platelet supplementation completely restored arachidonic acid-induced platelet aggregation in whole blood (10 vs. 1 V, P = 0.008) and platelet-rich plasma (73 vs. 5%, P < 0.01) in aspirin-treated samples, whereas it failed to correct ADP-induced aggregation (2 vs. 2 V in whole blood and 13.5 vs. 15% in platelet-rich plasma, P > 0.05) in ticagrelor-treated samples. We also report a case of a ticagrelor-treated patient in whom platelet transfusion failed to restore ADP-induced platelet aggregation.

Conclusion: Platelet supplementation restored platelet aggregation in aspirin-spiked but not in ticagrelor-spiked samples. These results do not support the use of platelet transfusion to reverse the effects of ticagrelor.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / toxicity
  • Adenosine Diphosphate / pharmacology
  • Arachidonic Acid / pharmacology
  • Aspirin / pharmacology
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / toxicity*
  • Platelet Function Tests
  • Platelet Transfusion*
  • Ticagrelor

Substances

  • Platelet Aggregation Inhibitors
  • Arachidonic Acid
  • Adenosine Diphosphate
  • Ticagrelor
  • Adenosine
  • Aspirin