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

Sasidhar Guthikonda, Kirankumar Mangalpally, Muthiah Vaduganathan, Rajnikant Patel, Timothy DeLao, Angela L. Bergeron, Jing Fei Dong, Eli I. Lev, Neal S. Kleiman

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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 B2 (TxB2) 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 (≥12%) to 1.5 mM AA. Baseline platelet aggregation with submaximal concentrations of agonists [ADP 2 μM, arachidonic acid (AA) 0.75 mM, collagen 0.375 and 0.5 μg/ml] was greater in AR subjects compared with non-AR subjects, but not with higher concentrations (ADP 5 μM and 20 μM,AA 1.5 mM and collagen 1 μg/ml). Post-aspirin platelet aggregation was elevated in AR subjects with both submaximal and maximal stimulation. Baseline and post-aspirin serum TxB2 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 ≤15% and 29/58 subjects having aggregation ≥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.

Original languageEnglish
Pages (from-to)83-89
Number of pages7
JournalThrombosis and Haemostasis
Volume100
Issue number1
DOIs
StatePublished - 1 Jul 2008
Externally publishedYes

Keywords

  • Aspirin resistance
  • Platelets
  • Thromboxane

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