Platelet count, not oxidative stress, may contribute to inadequate platelet inhibition by aspirin

Heterogeneity in platelet cyclooxygenase inhibition by aspirin in coronary artery disease

“…Increased platelet turnover may explain regained COX-1 function. More new platelets, non-exposed to aspirin, may be released, exhibiting uninhibited COX-1 activity which could lead to platelet aggregation [22,23]. Because the relation of TxA 2 formation to platelet aggregation is not linear and near complete inhibition of TxA 2 synthesis by aspirin is required to achieve sustained inhibition of platelet function, even a small increase in platelet turnover could lead to recovery of platelet aggregation in certain individuals [24,25].…”

Aspirin resistance: What the cardiologist needs to know?

“…Routine evaluation of aspirin resistance is not recommended, however in order to assess aspirin resistance in an individual patient, assays using aspirin-sensitive activation pathways, such as arachidonic acid-induced platelet responses, are preferable. The study of Lordkipanidzé et al, sheds some light on mechanisms underlying reduced response of platelets to the antiaggregatory effect of aspirin [3]. While, elevated levels of isoprostane formation, a marker of oxidative stress, failed to predict aspirin resistance in this study, increased platelet count, possibly reflecting enhanced platelet formation, was associated with increased risk of aspirin resistance.…”

“…In the present study 200 consecutive subjects suffering from stable coronary artery disease and under daily aspirin therapy were enrolled [3]. Inadequate platelet response to aspirin was defined as residual platelet aggregation ≥ 20% per arachidonic acid-induced light transmission aggregometry.…”

“…Because platelets lack the synthetic machinery to generate relevant amounts of new COX-1, aspirin-induced inhibition lasts for the lifetime of the platelet. In an elegant clinical study, published in this issue of the IJC by Lordkipanidzé et al,200 consecutive coronary artery disease (CAD) patients under daily aspirin therapy were enrolled, in order to define inadequate platelet response to aspirin and determine isoprostanes levels (8-iso-PGF 2α ) [3]. They observed intersubject variability in urinary 8-iso-PGF 2α levels which were similar between aspirin responders and non-responders.…”

Effect of common single nucleotide polymorphisms in COX-1 gene on related metabolic activity in diabetic patients treated with acetylsalicylic acid

“…Because 8-iso-PGF2α formation might correlate with the rate of TxA 2 biosynthesis, it was hypothesized that increased oxidant stress in T2DM could induce enhanced generation of 8-iso-PGF2α, which can contribute to platelet activation [ 24 ]. Even if it was demonstrated previously that enhanced 8-iso-PGF2α synthesis may be associated with advanced age, cigarette smoking, hypercholesterolemia, and unstable angina, as well as after coronary artery reperfusion, the role of 8-iso-PGF2α in ASA's effect on TxA 2 synthesis remains uncertain [ 25 – 33 ].…”