title: Relationship between Inflammation and Aspirin and Clopidogrel Antiplatelet Responses in Acute Ischemic Stroke.
abstract: OBJECTIVE
  We measured serum levels of proinflammatory/prothrombotic markers P-selectin, CD40L, matrix metalloproteinase 9 (MMP-9), intracellular adhesion molecule 1 (ICAM-1), and interleukin (IL)-6 in ischemic stroke patients, correlating their levels with the results of aspirin (ASA) and clopidogrel antiplatelet responses, using 3 "point of care" platelet function instruments, thromboelastograph (TEG), Accumetrics (ACU), and impedance aggregometer (IMP).
  
  
  METHODS
  Patients on chronic ASA regimen at the time of stroke were switched to 300 mg clopidogrel loading dose and 75 mg clopidogrel maintenance dose. Serum levels of the aforementioned inflammatory mediators were measured in 51 patients at baseline (on ASA regimen), and at 26 ± 5 hours and 64 ± 18 hours postclopidogrel administration by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  P-selectin, CD40L, and MMP-9 serum levels were reduced; ICAM-1 and IL-6 serum levels showed no difference postclopidogrel administration relative to baseline. Patients' stratification based on ASA dose showed more significant reductions in P-selectin, CD40L, and MMP-9 serum levels postclopidogrel administration in patients who were on baseline 81 mg ASA, as compared to patients on 325 mg ASA. Measurement with TEG was sensitive for correlating ASA antiplatelet responses to serum levels of inflammatory markers, whereas measurements with ACU and IMP were sensitive for correlating clopidogrel antiplatelet responses to serum levels of inflammatory markers.
  
  
  CONCLUSIONS
  Clopidogrel exerts both platelet-dependent and platelet-independent anti-inflammatory effects. The association between platelet function and inflammation depends on the platelet function analyzer, the type of antiplatelet agent, the nature of the inflammatory marker, and the time of measurement relative to the time of drug administration.
authors.affiliation: Department of Neurology, Stroke Center, Buffalo Medical Center, Buffalo, New York. Electronic address: zs2@buffalo.edu.
authors.forename: Zohara
authors.initials: Z
authors.lastname: Sternberg
authors.affiliation: Department of Neurology, Stroke Center, Buffalo Medical Center, Buffalo, New York.
authors.forename: Trevor
authors.initials: T
authors.lastname: Chichelli
authors.affiliation: Department of Neurology, Stroke Center, Buffalo Medical Center, Buffalo, New York.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sternberg
authors.affiliation: Department of Neurology, Stroke Center, Buffalo Medical Center, Buffalo, New York.
authors.forename: Robert
authors.initials: R
authors.lastname: Sawyer
authors.affiliation: Department of Neurology, Stroke Center, Buffalo Medical Center, Buffalo, New York.
authors.forename: Marilou
authors.initials: M
authors.lastname: Ching
authors.affiliation: Department of Emergency Medicine, Buffalo Medical Center, Buffalo, New York.
authors.forename: David
authors.initials: D
authors.lastname: Janicke
authors.affiliation: Department of Internal Medicine, Buffalo Medical Center, Buffalo, New York.
authors.forename: Julian L
authors.initials: JL
authors.lastname: Ambrus
authors.affiliation: Department of Biostatistics, University of Buffalo, Buffalo, New York.
authors.forename: Jinhee
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Neurology, Stroke Center, Buffalo Medical Center, Buffalo, New York.
authors.forename: Frederick
authors.initials: F
authors.lastname: Munschauer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood* / Q000517:prevention & control; D023201:CD40 Ligand / Q000097:blood; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D055502:Secondary Prevention; D020521:Stroke / Q000097:blood* / Q000517:prevention & control; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D018799:Intercellular Adhesion Molecule-1; D023201:CD40 Ligand; D000077144:Clopidogrel; D020780:Matrix Metalloproteinase 9; D013988:Ticlopidine; D001241:Aspirin
keywords: Antiplatelet agents; inflammatory markers; platelet function analyzer; point of care