title: Time-dependent changes in non-COX-1-dependent platelet  function with daily aspirin therapy.
abstract: 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.
authors.affiliation: Institute for Genome Sciences and Policy, Duke University, 905 S. Lasalle Dr., DUMC Box 3445, Durham, NC 27710, USA. deepak.voora@duke.edu
authors.forename: Deepak
authors.initials: D
authors.lastname: Voora
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Ortel
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Lucas
authors.forename: Jen-Tsan
authors.initials: JT
authors.lastname: Chi
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Ginsburg
mesh_terms: D000328:Adult; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology*; D015331:Cohort Studies; D051545:Cyclooxygenase 1; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010979:Platelet Function Tests / Q000379:methods; D013997:Time Factors; D055815:Young Adult
chemical_list: D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D001241:Aspirin