Effects of ex vivo platelet supplementation on platelet aggregability in blood samples from patients treated with acetylsalicylic acid, clopidogrel, or ticagrelor

Br J Anaesth. 2014 Mar;112(3):570-5. doi: 10.1093/bja/aet339. Epub 2013 Oct 22.

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.

Keywords: haemorrhage; haemostasis, surgical; platelet aggregation inhibitors; platelet transfusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / pharmacology
  • Adenosine Diphosphate
  • Aged
  • Arachidonic Acid / pharmacology
  • Aspirin / pharmacology*
  • Clopidogrel
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / pharmacology
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation / physiology*
  • Platelet Aggregation Inhibitors / pharmacology*
  • Platelet Transfusion*
  • Ticagrelor
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacology

Substances

  • Peptide Fragments
  • Platelet Aggregation Inhibitors
  • thrombin receptor peptide (42-47)
  • Arachidonic Acid
  • Adenosine Diphosphate
  • Clopidogrel
  • Ticagrelor
  • Adenosine
  • Ticlopidine
  • Aspirin