Thromboxane Formation Assay to Identify High On-Treatment Platelet Reactivity to Aspirin

Abstract

Platelet inhibition by aspirin is indispensable in the secondary prevention of cardiovascular events. Nevertheless, impaired aspirin antiplatelet effects (high on-treatment platelet reactivity [HTPR]) are frequent. This is associated with an enhanced risk of cardiovascular events. The current gold standard to evaluate platelet hyper-reactivity despite aspirin intake is the light-transmittance aggregometry (LTA). However, pharmacologically, the most specific test is the measurement of arachidonic acid (AA)-induced thromboxane (TX) B2 formation. Currently, the optimal cut-off to define HTPR to aspirin by inhibition of TX formation is not known. Therefore, in this pilot study, we aimed to calculate a TX formation cut-off value to detect HTPR defined by the current gold standard LTA. We measured platelet function in 2,507 samples. AA-induced TX formation by ELISA and AA-induced LTA were used to measure aspirin antiplatelet effects. TX formation correlated nonlinearly with the maximum of aggregation in the AA-induced LTA (Spearman's rho R = 0.7396; 95% CI 0.7208-0.7573, p < 0.0001). Receiver operating characteristic analysis and Youden's J statistics revealed 209.8 ng/mL as the optimal cut-off value to detect HTPR to aspirin with the TX ELISA (area under the curve: 0.92, p < 0.0001, sensitivity of 82.7%, specificity of 90.3%). In summary, TX formation ELISA is reliable in detecting HTPR to aspirin. The calculated cut-off level needs to be tested in trials with clinical end points.

Aspirin intake in the morning is associated with suboptimal platelet inhibition, as measured by serum Thromboxane B2, during infarct-prone early-morning hours

“…These fixed time points increase the comparability of every regimen. Furthermore, although not all parameters of platelet function tests showed statistically significant results-as the thromboxane production is the primary target of aspirin-sTxB 2 levels can be seen as the most specific test for aspirin effectivity [31]. An important limitation, however, lies in the technical properties of the Platelet Function Analyser (PFA).…”

Relationship between the changes in thromboxane B2, 6-keto-prostaglandin Fla, and blood glucose levels and progressive ischemic stroke

“…The high expression of BG in stroke patients will increase the anaerobic glycolysis of ischemic stroke, aggravate the accumulation of lactic acid, and eventually lead to stroke metabolic disorders (12,13). Kong et al (14) reported that TXB 2 is expressed at a low level in blood in a normal state, but when platelets are activated, a large amount of TXB 2 is released into blood, which has the effect of promoting platelet aggregation and vasoconstriction.…”

Mechanism of Improving Aspirin Resistance: Blood-Activating Herbs Combined With Aspirin in Treating Atherosclerotic Cardiovascular Diseases

“…However, the AR standard most commonly used and accepted by researchers is that the average aggregation of 10 μmol/L adenosine diphosphate (ADP) is greater than 70%, and the average aggregation of 0.5 mg/ml AA is greater than 20% as proposed by Gum et al (2001). Mohring et al (2017) detected the formation of thromboxane induced by AA through enzyme-linked immunosorbent assay (ELISA) and the AA-induced antiplatelet effect of aspirin by the LTA method. The results showed that there was a non-linear correlation between the formation of thromboxane and the maximum value of AA-induced LTA aggregation (Spearman's rho R 0.7396; 95% CI 0.7208-0.7573, p < 0.0001).…”