Increased platelet expression of glycoprotein IIIa following aspirin treatment in aspirin‐resistant but not aspirin‐sensitive subjects

Abstract

Aims Aspirin is widely used as an anti‐platelet agent for cardiovascular prophylaxis. Despite aspirin treatment, many patients experience recurrent thrombotic events, and aspirin resistance may contribute to this. We examined the prevalence of aspirin resistance in a healthy population, and investigated whether the platelet proteome differed in aspirin‐resistant subjects. Methods Ninety‐three healthy subjects received aspirin 300 mg daily for 28 days. Before and at the end of treatment, urine was taken to determine 11‐dehydrothromboxane B2, and blood was taken to measure arachidonic acid (AA)‐induced aggregation of platelet‐rich plasma and to interrogate the platelet proteome by mass spectrometric analysis with further confirmation of findings using Western blotting. Results In two of the 93 subjects, neither AA‐induced aggregation nor urinary 11‐dehydrothromboxane B2 was effectively suppressed by aspirin, despite measurable plasma salicylate concentrations, suggesting the presence of true aspirin resistance. Despite no detectable differences in the platelet proteome at baseline, following aspirin a marked increase was seen in platelet glycoprotein IIIa expression in the aspirin‐resistant but not aspirin‐sensitive subjects. An increase in platelet glycoprotein IIIa expression with aspirin resistance was confirmed in a separate cohort of 17 patients with stable coronary artery disease on long term aspirin treatment, four of whom exhibited aspirin resistance. Conclusions In a healthy population, true aspirin resistance is uncommon but exists. Resistance is associated with an increase in platelet glycoprotein IIIa expression in response to aspirin. These data shed new light on the mechanism of aspirin resistance, and provide the potential to identify aspirin‐resistant subjects using a novel biomarker.

Deciphering glycomics and neuroproteomic alterations in experimental traumatic brain injury: Comparative analysis of aspirin and clopidogrel treatment

“…Floyd et al. has demonstrated that glycoprotein IIIa (A isoform) expression has been increased in lysed platelets . Besides, a significant increase in the acetylation rate and a significant decrease in glycation have been reported by Finamore et al.…”

“…Two of the most widely used antiplatelet therapies include aspirin (ASA) and clopidogrel (CLOP). ASA irreversibly inhibits the platelets from producing thromboxane A 2 through acetylation of the cyclo‐oxygenase‐1 enzyme at Ser‐529 residue while CLOP acts by binding specifically and irreversibly to the platelet P2RY12 purinergic receptor, inhibiting ADP‐mediated platelet activation and aggregation . Numerous studies assessing the impact of antiplatelet agents on TBI have been proposed.…”

“…Floyd et al. and Finamore et al. conducted several studies concerning the alteration that ASA and CLOP induce on PTMs.…”

Nonsteroidal anti-inflammatory drugs in-vitro and in-vivo treatment and Multidrug Resistance Protein 4 expression in human platelets

“…MRP4 might also reduce cytosolic concentrations of cAMP e cGMP as it functions as a negative regulator that in turn limits the effect of platelet cyclic nucleotides [24]. It is possible that chronic NSAIDs treatment may determine up-regulation of other proteins as well as MRP4, parallel to what has been seen after chronic aspirin treatment [25,26]. This study has excluded that platelet hyper-reactivity could depend on an increased TxB2 release as we demonstrated that arachidonic acid induced TxB2 production is the same in OA patients, with high levels of MRP4, and in the control population.…”

Aspirin resistance in coronary heart disease: Current understandings and strategies

“…This finding offers new clues to the mechanism of aspirin resistance, and also suggests that platelet GPIIIa receptor may become a novel biomarker for aspirin resistance. [13] In another study, aspirin resistance was found to correlate with age, and the incidence of aspirin resistance was high in patients with coronary heart disease (CHD) aged 75 years or above. [14] It was also shown that enteric-coated aspirin may cause aspirin resistance, and therefore low-dose enteric-coated aspirin as a medication for secondary prevention of cardiovascular diseases may not achieve complete inhibition of platelet COX due to inadequate bioavailability.…”