title: Aspirin resistance may be identified by miR-92a in plasma combined with platelet distribution width.
abstract: OBJECTIVE
  Aspirin is a widely used drug for prevention of thrombotic events in cardiovascular patients, but approximately 25% of patients experience insufficient platelet inhibition due to aspirin, and remain in risk of cardiovascular events. This study aimed to investigate the value of circulating miR-92a and platelet size as biomarkers of the individual response to aspirin therapy.
  
  
  METHODS
  Blood samples were collected from 50 healthy blood donors without antithrombotic medication and 50 patients with intermittent claudication on daily aspirin therapy. Based on results from the arachidonic acid stimulated aggregation test on Multiplate®analyzer (ASPItest), patients were defined as aspirin resistant (n=10) or aspirin responders (n=40). Plasma levels of miR-92a were evaluated by RT-qPCR analysis and platelet distribution width (PDW) was used to assess platelet size variability. Receiver operating characteristic curves for miR-92a levels and PDW were used to set cut-off values for discrimination between aspirin responding and aspirin resistant patients.
  
  
  RESULTS
  When defining aspirin resistance as an ASPItest ≥30U, the optimal cut-off values for discrimination of aspirin responders and aspirin resistant patients were found to be PDW>11.8fL and a relative expression level of miR-92a>4.5. Using these cut-off values we could define a PDW/miR-92a-score with a specificity of 97.5% and a sensitivity of 80.0% in relation to detect aspirin resistance. The corresponding positive and negative predictive values were found to be 88.9% and 95.1%, respectively.
  
  
  CONCLUSIONS
  Aspirin resistance can potentially be identified by miR-92a levels in plasma combined with PDW.
authors.affiliation: Department of Clinical Immunology and Biochemistry, Lillebaelt Hospital, Kabbeltoft 25, 7100 Vejle and Skovvangen 2-8, 6000 Kolding, Denmark. Electronic address: Helle.Glud.Binderup@rsyd.dk.
authors.forename: Helle Glud
authors.initials: HG
authors.lastname: Binderup
authors.affiliation: Department of Vascular Surgery, Lillebaelt Hospital, Skovvangen 2-8, 6000 Kolding, Denmark; Institute of Regional Health Research, University of Southern Denmark, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Houlind
authors.affiliation: Department of Clinical Immunology and Biochemistry, Lillebaelt Hospital, Kabbeltoft 25, 7100 Vejle and Skovvangen 2-8, 6000 Kolding, Denmark; Institute of Regional Health Research, University of Southern Denmark, Denmark.
authors.forename: Jonna Skov
authors.initials: JS
authors.lastname: Madsen
authors.affiliation: Department of Clinical Immunology and Biochemistry, Lillebaelt Hospital, Kabbeltoft 25, 7100 Vejle and Skovvangen 2-8, 6000 Kolding, Denmark.
authors.forename: Claus Lohman
authors.initials: CL
authors.lastname: Brasen
mesh_terms: D000328:Adult; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000166:cytology*; D016022:Case-Control Studies; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007383:Intermittent Claudication / Q000097:blood; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D010974:Platelet Aggregation
chemical_list: C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D001241:Aspirin
keywords: Anti-platelet therapy; Aspirin resistance; Biomarker; MicroRNA-92a; PDW