title: Effects of ex vivo platelet supplementation on platelet aggregability in blood samples from patients treated with acetylsalicylic acid, clopidogrel, or ticagrelor.
abstract: BACKGROUND
  Transfusion of platelet concentrate is often used to treat bleeding in patients on platelet inhibitors, but little is known about its efficacy between different inhibitors. We assessed the effect of ex vivo platelet supplementation on platelet aggregability in blood samples from patients treated with acetylsalicylic acid (ASA), clopidogrel, or ticagrelor.
  
  
  METHODS
  Platelet aggregability was investigated with multiple electrode aggregometry with adenosine diphosphate (ADP), arachidonic acid (to assess ASA-dependent aggregability), and thrombin receptor activating peptide-6 (TRAP) as activators in whole-blood samples from patients treated with ASA (n=10), ASA+clopidogrel (n=15), or ASA+ticagrelor (n=15), and from healthy controls (n=10). Aggregability was measured before and after supplementation of AB0-compatible fresh apheresis platelets (+46, +92, and +138×10(9) litre(-1)).
  
  
  RESULTS
  Both ASA-dependent and ADP-dependent aggregability improved in a dose-dependent fashion after platelet supplementation. ASA-dependent aggregability was completely restored in all patient groups, but there was only a small improvement in ADP-dependent aggregability in patients on dual antiplatelet therapy. There was less effect of platelet supplementation on ADP- and ASA-dependent aggregability in ticagrelor-treated patients than in clopidogrel-treated patients [3.9 (95% confidence interval 1.6-6.3) vs 9.0 (5.2-12.8) AU×min (P=0.021) and 48 (36-59) vs 69 (60-78) AU×min (P=0.004), respectively, at the highest platelet dose].
  
  
  CONCLUSIONS
  Platelet supplementation improved platelet aggregability independently of antiplatelet therapy. The effect on ADP-dependent platelet inhibition was limited however. Reduced effect of platelet transfusion is more likely within 2 h of drug intake in patients treated with ASA+ticagrelor compared with ASA+clopidogrel.
authors.affiliation: Department of Cardiothoracic Surgery.
authors.forename: E C
authors.initials: EC
authors.lastname: Hansson
authors.forename: C
authors.initials: C
authors.lastname: Shams Hakimi
authors.forename: K
authors.initials: K
authors.lastname: Åström-Olsson
authors.forename: C
authors.initials: C
authors.lastname: Hesse
authors.forename: H
authors.initials: H
authors.lastname: Wallén
authors.forename: M
authors.initials: M
authors.lastname: Dellborg
authors.forename: P
authors.initials: P
authors.lastname: Albertsson
authors.forename: A
authors.initials: A
authors.lastname: Jeppsson
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000244:Adenosine Diphosphate; D000368:Aged; D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D017713:Platelet Transfusion; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; C082835:thrombin receptor peptide (42-47); D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine; D001241:Aspirin
keywords: haemorrhage; haemostasis, surgical; platelet aggregation inhibitors; platelet transfusion