Time-dependent changes in non-COX-1-dependent platelet function with daily aspirin therapy.

Journal Article

To develop an integrated metric of non-COX-1-dependent platelet function (NCDPF) to measure the temporal response to aspirin in healthy volunteers and diabetics. NCDPF on aspirin demonstrates wide variability, despite suppression of COX-1. Although a variety of NCDPF assays are available, no standard exists and their reproducibility is not established. We administered 325 mg/day aspirin to two cohorts of volunteers (HV1, n = 52, and HV2, n = 96) and diabetics (DM, n = 74) and measured NCDPF using epinephrine, collagen, and ADP aggregometry and PFA100 (collagen/epi) before (Pre), after one dose (Post), and after several weeks (Final). COX-1 activity was assessed with arachidonic acid aggregometry (AAA). The primary outcome of the study, the platelet function score (PFS), was derived from a principal components analysis of NCDPF measures. The PFS strongly correlated with each measure of NCDPF in each cohort. After 2 or 4 weeks of daily aspirin the Final PFS strongly correlated (r > 0.7, P < 0.0001) and was higher (P < 0.01) than the Post PFS. The magnitude and direction of the change in PFS (Final–Post) in an individual subject was moderately inversely proportional to the Post PFS in HV1 (r = -0.45), HV2 (r = -0.54), DM (r = -0.68), P < 0.0001 for all. AAA remained suppressed during aspirin therapy. The PFS summarizes multiple measures of NCDPF. Despite suppression of COX-1 activity, NCDPF during aspirin therapy is predictably dynamic: those with heightened NCDPF continue to decline whereas those with low/normal NCDPF return to pre-aspirin levels over time.

Full Text

Duke Authors

Cited Authors

  • Voora, D; Ortel, TL; Lucas, JE; Chi, J-T; Becker, RC; Ginsburg, GS

Published Date

  • April 2012

Published In

Volume / Issue

  • 33 / 3

Start / End Page

  • 246 - 257

PubMed ID

  • 22294277

Electronic International Standard Serial Number (EISSN)

  • 1573-742X

Digital Object Identifier (DOI)

  • 10.1007/s11239-012-0683-0

Language

  • eng

Conference Location

  • Netherlands