Malondialdehyde Assay in the Evaluation of Aspirin Antiplatelet Effects

Pharmacology. 2019;103(1-2):23-29. doi: 10.1159/000493754. Epub 2018 Oct 24.

Abstract

Aspirin is essential in secondary prevention of patients after myocardial infarction and with coronary artery disease. However, impaired pharmacodynamic response to aspirin is frequent (high on-treatment platelet reactivity [HTPR]). This leads to an enhanced prevalence of cardiovascular events and to an impaired clinical outcome. The current specific assays to evaluate aspirin antiplatelet effects are complex, time-consuming and demand for a high laboratory expertise. Therefore, we developed a potentially bedside assay based on the determination of malondialdehyde (MDA). MDA is a by-product of the thromboxane (TX) formation, which is synthesized in equimolar concentrations. In this study, we compared this MDA assay to the conventional assays in determination of pharmacodynamic aspirin response. For this, aspirin antiplatelet effects were measured in 22 healthy individuals and 63 aspirin treated patients using TX B2 formation enzyme-linked antibody assay, arachidonic acid induced light transmission aggregometry (LTA) and the new fluorometric MDA assay. In patients, MDA levels correlated well with TX formation (R = 0.81; 95% CI 0.69-0.88; p < 0.001) and LTA (R = 0.84; CI 0.74-0.91; p < 0.001). Receiver operating characteristic analyses revealed that the MDA assay does detect HTPR to aspirin sufficiently (area under the curve: 0.965; p < 0.001). The optimal cut-off was > 128 nmol/L (sensitivity of 100%, specificity of 91%). The new MDA assay is reliable in detecting HTPR. It is highly specific in the evaluation of antiplatelet effects by aspirin. This promising and potential bedside assay needs to be evaluated in clinical practice.

Keywords: Aspirin; High on-treatment platelet reactivity; Malondialdehyde.

MeSH terms

  • Aged
  • Aspirin / blood
  • Aspirin / pharmacokinetics
  • Aspirin / pharmacology*
  • Blood Platelets / drug effects*
  • Case-Control Studies
  • Female
  • Humans
  • Male
  • Malondialdehyde / blood*
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Function Tests
  • Thromboxane B2 / blood

Substances

  • Platelet Aggregation Inhibitors
  • Malondialdehyde
  • Thromboxane B2
  • Aspirin