Multiplate® evaluation of acetylsalicylic acid efficacy in carotid surgery: routine and genetic influencing factors

• Published in: Journal of thrombosis and haemostasis 2018-03, Vol.16 (3), p.583-591
• Main Authors: Roullet, S., Labrouche, S., Carrie, C., Auque, H., Berard, X., Freyburger, G.
• Format: Article
• Language: English
• Subjects: Acetylsalicylic acid; Aged; Aged, 80 and over; Arachidonic acid; Aspirin; Aspirin - therapeutic use; ATP Binding Cassette Transporter, Subfamily B - genetics; Carotid Arteries - surgery; carotid endarterectomy; Cluster Analysis; Cyclooxygenase 1 - genetics; Deoxyribonucleic acid; DNA; Endarterectomy, Carotid - methods; Female; Fibrinogen; Fibrinogen - analysis; Genomics; Hematocrit; hierarchical clustering; Human health and pathology; Humans; Integrin alpha2 - genetics; Integrin beta1 - genetics; Life Sciences; Male; Middle Aged; Multiplate; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - therapeutic use; Platelet Count; Platelet Function Tests; Platelets; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Receptors, Adrenergic, alpha-2 - genetics; Receptors, Cell Surface - genetics; Receptors, Thromboxane A2, Prostaglandin H2 - genetics; Sequence Analysis, DNA; Single-nucleotide polymorphism; single‐nucleotide polymorphisms; Surgery
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/jth.13943

Essentials Acetylsalicylic acid (ASA) is prescribed to patients scheduled for carotid endarterectomy (CEA). We measured ASA efficacy during CEA by Multiplate® and searched for influencing factors. Most patients scheduled for CEA and treated by ASA are sensitive to this therapy. Influencing genomic factors are involved in ASA metabolism and in platelet function modulations. Summary Background Acetylsalicylic acid (ASA) is recommended before, during and after carotid endarterectomy (CEA). The efficacy of ASA is influenced by numerous biological and genotypic factors. Objectives To determine the biological efficacy of ASA by using the Multiplate® method, and to explore the biological parameters and genomic factors influencing this efficacy. Methods This descriptive cross‐sectional study included all patients scheduled for CEA between January 2012 and April 2013. Multiplate® tests were performed at day 0 and day 30. A set of 66 single‐nucleotide polymorphisms (SNPs) from 38 genes or DNA regions were selected and studied along with phenotypic parameters by the use of hierarchical clustering (HC) for multidimensional data management. Results Fifty‐five patients receiving ASA were analyzed. Of the patients, 95% were found to be sensitive to ASA, with values under the threshold of normality (400 AU min–1). However, there were notable differences in residual aggregation among subjects over a wide range. HC revealed four subclusters comprising three categories of parameters: (i) routine and functional parameters – in ASA‐treated patients, the ASPItest was highly linked to the ADPtest, to platelet count, and, to a lesser extent, to fibrinogen and hematocrit; (ii) polymorphisms in genes involved in ASA absorption and in the arachidonic acid pathway (ABCB1 and COX‐1); and (iii) polymorphisms in genes modulating basal platelet function, i.e. TBXA2R, ADRA2A, PEAR1, ITGA2 and ITGB1. Conclusion Most patients treated with ASA before CEA were sensitive to it, according to Multiplate® ASPItest results. Genomic factors influencing this efficacy are SNPs involved in ASA absorption and metabolic pathway, and in modulations in basal platelet function.