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


METHODS
In vitro study.


METHODS
Blood samples were obtained from the French Blood Bank Institute.


METHODS
Healthy blood donors.


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


METHODS
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.


CONCLUSIONS
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.
From the Inserm UMR-S1140, Faculté de Pharmacie (A-CM, CB, LC, BD, PG, IG-T, C-MS, CB-L, AG), Université Paris Descartes, Sorbonne Paris Cité (A-CM, CB, LC, BD, PG, IG-T, C-MS, CB-L, AG), Hôpital Val de Grâce, Service de Cardiologie (A-CM), AP-HP, Hôpital Cochin, Laboratoire d'hématologie (LC, IG-T), Institut Mutualiste Montsouris, Service d'Anesthésie-Réanimation (IP), AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique (PG), AP-HP, Hôpital Cochin, Service d'Anesthésie-Réanimation (C-MS), and Fondation Adolphe de Rothschild, Service d'Anesthésie-Réanimation, Paris, France (AG).
Anne-Céline
AC
Martin
Célia
C
Berndt
Leyla
L
Calmette
Ivan
I
Philip
Benoit
B
Decouture
Pascale
P
Gaussem
Isabelle
I
Gouin-Thibault
Charles-Marc
CM
Samama
Christilla
C
Bachelot-Loza
Anne
A
Godier
D000241:Adenosine / Q000031:analogs & derivatives* / Q000633:toxicity; D000244:Adenosine Diphosphate / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000633:toxicity*; D010979:Platelet Function Tests; D017713:Platelet Transfusion; D000077486:Ticagrelor
D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D000077486:Ticagrelor; D000241:Adenosine; D001241:Aspirin