title: Increased platelet sensitivity among individuals with aspirin resistance - platelet aggregation to submaximal concentration of arachidonic acid predicts response to antiplatelet therapy.
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.
authors.affiliation: Methodist DeBakey Heart Center, 6565 Fannin, F1090, Houston, TX 77030, USA.
authors.forename: Sasidhar
authors.initials: S
authors.lastname: Guthikonda
authors.forename: Kirankumar
authors.initials: K
authors.lastname: Mangalpally
authors.forename: Muthiah
authors.initials: M
authors.lastname: Vaduganathan
authors.forename: Rajnikant
authors.initials: R
authors.lastname: Patel
authors.forename: Timothy
authors.initials: T
authors.lastname: Delao
authors.forename: Angela L
authors.initials: AL
authors.lastname: Bergeron
authors.forename: Jing-Fei
authors.initials: JF
authors.lastname: Dong
authors.forename: Eli I
authors.initials: EI
authors.lastname: Lev
authors.forename: Neal S
authors.initials: NS
authors.lastname: Kleiman
mesh_terms: D000244:Adenosine Diphosphate; D000328:Adult; D016718:Arachidonic Acid; D001241:Aspirin / Q000494:pharmacology* / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D003094:Collagen; D051545:Cyclooxygenase 1 / Q000097:blood; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D010979:Platelet Function Tests; D011237:Predictive Value of Tests; D017482:Receptors, Thromboxane / Q000097:blood / Q000187:drug effects; D012016:Reference Values; D013929:Thromboxane B2 / Q000097:blood; D017211:Treatment Failure
chemical_list: D016861:Cyclooxygenase Inhibitors; D010975:Platelet Aggregation Inhibitors; D017482:Receptors, Thromboxane; D016718:Arachidonic Acid; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D003094:Collagen; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D001241:Aspirin