Serum thromboxane B2 but not soluble P-selectin levels identify ischemic stroke patients with persistent platelet reactivity while on aspirin therapy

Pandarisamy Sundaravadivel; Rita Christopher; Nitin Ramanujam; Sadanandavalli Retnaswami Chandra

doi:10.1016/j.thromres.2021.10.021

Serum thromboxane B2 but not soluble P-selectin levels identify ischemic stroke patients with persistent platelet reactivity while on aspirin therapy

Thromb Res. 2021 Dec:208:92-98. doi: 10.1016/j.thromres.2021.10.021. Epub 2021 Oct 28.

Authors

Pandarisamy Sundaravadivel¹, Rita Christopher², Nitin Ramanujam¹, Sadanandavalli Retnaswami Chandra³

Affiliations

¹ Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Bengaluru, India.
² Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Bengaluru, India. Electronic address: rita@nimhans.ac.in.
³ Department of Neurology, National Institute of Mental Health and Neuro Sciences, Bengaluru, India.

PMID: 34742142
DOI: 10.1016/j.thromres.2021.10.021

Abstract

Background: Aspirin non-response due to persistent platelet reactivity has been associated with adverse vascular events. Light transmission aggregometry (LTA), the 'gold standard' for measuring the platelet response to aspirin therapy, is a cumbersome procedure and a simple and reliable alternative is required. Our aim was to explore whether serum thromboxane B2 (sTXB2) and soluble P-selectin can be used to identify patients who are at risk of increased platelet reactivity while on aspirin.

Methods and results: We recruited 293 ischemic stroke patients, taking aspirin for more than seven days, and performed LTA to classify them. Based on therapeutic serum salicylate levels, 63 patients were excluded due to suspected non-compliance, followed by ELISA measurement of TXB2 and P-selectin in serum. Accordingly, patients were classified into 'Responders' (n = 122, 53%), 'Semi-responders' (n = 76, 33%) and 'Non-responders' (n=32, 14%) by LTA. Patients who had platelet aggregation of ≥70% with 10μM ADP and ≥20% with 0.5mM AA were defined as 'Non-responders'. In comparison with 'Responders', 'Non-responders' had 8.63-fold increased risk of secondary vascular events (p = 0.008). ROC curve analysis revealed that sTXB2, at a cut-off level of >4.15 ng/mL, could distinguish the patient group with elevated platelet reactivity with a sensitivity of 84.3% (AUC = 0.84), and was in fair agreement with the LTA-based classification of patients. Soluble P-selectin levels, on the other hand, had no discriminatory ability.

Conclusion: We suggest sTXB2 measurement as an alternative to the LTA approach for identifying aspirin-treated ischemic stroke patients who are at risk of enhanced platelet reactivity and subsequent vascular events.

Keywords: Aspirin therapy; Ischemic stroke; Light transmission aggregometry; Soluble P-selectin; Thromboxane B2.

MeSH terms

Aspirin* / therapeutic use
Brain Ischemia* / blood
Brain Ischemia* / diagnosis
Humans
Ischemic Stroke* / blood
Ischemic Stroke* / diagnosis
P-Selectin / blood*
Thromboxane B2 / blood*

Substances

P-Selectin
Thromboxane B2
Aspirin