Increased platelet sensitivity among individuals with aspirin resistance - Platelet aggregation to submaximal concentration of arachidonic acid predicts response to antiplatelet therapy Academic Article uri icon

Overview

MeSH Major

  • Arachidonic Acid
  • Aspirin
  • Blood Platelets
  • Drug Resistance
  • Platelet Aggregation
  • Platelet Aggregation Inhibitors

abstract

  • Aspirin 'resistance' (AR) is a phenomenon of uncertain etiology describing decreased platelet inhibition by aspirin. We studied whether (i) platelets in AR demonstrate increased basal sensitivity to a lower degree of stimulation and (ii) platelet aggregation with submaximal stimulation could predict responses to aspirin. Serum thromboxane B(2) (TxB(2)) levels and platelet aggregation with light transmission aggregometry (LTA) were measured at baseline and 24 hours after 325 mg aspirin administration in 58 healthy subjects. AR was defined as the upper sixth of LTA (> or = 12%) to 1.5 mM AA. Baseline platelet aggregation with submaximal concentrations of agonists [ADP 2 microM, arachidonic acid (AA) 0.75 mM, collagen 0.375 and 0.5 microg/ml] was greater in AR subjects compared with non-AR subjects, but not with higher concentrations (ADP 5 microM and 20 microM, AA 1.5 mM and collagen 1 microg/ml). Post-aspirin platelet aggregation was elevated in AR subjects with both submaximal and maximal stimulation. Baseline and post-aspirin serum TxB(2) were higher in AR subjects and decreased further with ex-vivo COX-1 inhibition, suggesting incompletely suppressed COX-1 activity. Pre-aspirin platelet aggregation to 0.75 AA demonstrated a dichotomous response with 29/58 subjects having aggregation < or = 15% and 29/58 subjects having aggregation > or = 75%. In the high aggregation group 28% had AR compared to 6% in the non-AR group (p = 0.04). In conclusion, platelets in AR subjects demonstrate increased basal sensitivity to submaximal stimulation, which could predict responses to antiplatelet therapy.

publication date

  • July 2008

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1160/TH07-10-0590

PubMed ID

  • 18612542

Additional Document Info

start page

  • 83

end page

  • 9

volume

  • 100

number

  • 1