Increased platelet sensitivity among individuals with aspirin resistance – Platelet aggregation to submaximal concentration of arachidonic acid predicts response to antiplatelet therapy
Sasidhar Guthikonda1, Kirankumar Mangalpally1, Muthiah Vaduganathan1, Rajnikant Patel2, Timothy DeLao1, Angela L. Bergeron3, Jing-Fei Dong3, Eli I. Lev1, Neal S. Kleiman1
1The Methodist Hospital Research Institute and The Methodist DeBakey Heart and Vascular Center, Houston, Texas, USA; 2Department of Cardiology, Sun Health Boswell Hospital, Boswell, Arizona, USA; 3Department of Thrombosis, Baylor College of Medicine, Houston, Texas, USA
Aspirin ‘resistance’ (AR) is a phenomenon of uncertain etiology describing decreased platelet inhibition by aspirin. We studied whether (i) platelets inAR 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 serumTxB2 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.
Platelets, thromboxane, Aspirin resistance