Time-dependent changes in non-COX-1-dependent platelet function with daily aspirin therapy.
Journal Article (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
- Becker, Richard Clinton
- Chi, Jen-Tsan Ashley
- Ginsburg, Geoffrey Steven
- Ortel, Thomas Lee
- Voora, Deepak
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
Pubmed Central ID
- PMC3337886
Electronic International Standard Serial Number (EISSN)
- 1573-742X
Digital Object Identifier (DOI)
- 10.1007/s11239-012-0683-0
Language
- eng
Conference Location
- Netherlands