title: TXA2 synthesis and COX1-independent platelet reactivity in aspirin-treated patients soon after acute cerebral stroke or transient ischaemic attack.
abstract: BACKGROUND
  The pharmacological target of aspirin is the inhibition of cyclooxygenase-1 (COX1) and thromboxane-A2 (TX) synthesis. Very few data are available on TX assessment in patients with stroke. We studied platelet TX synthesis, COX1-independent platelet reactivity, the influence of platelet-erythrocyte interactions and the potential association between platelet responses and the severity of stroke, evaluated with a clinical score (NIHSS).
  
  
  METHODS
  We examined 157 aspirin-treated patients with acute stroke or TIA, 128 aspirin-free and 15 aspirin-treated healthy subjects (HS). Collagen-induced TX, platelet recruitment in whole blood and platelets ± erythrocytes (haematocrit 40%) were assessed in patients on daily-aspirin within three days from onset. Arachidonic-acid-, ADP-, thrombin-receptor activating peptide TRAP-, and collagen-induced aggregation were also evaluated.
  
  
  RESULTS
  Partial TX inhibition (<95% inhibition vs aspirin-free controls) was observed in 13% of patients. This was associated with marked increases in COX1-dependent responses (arachidonic-acid- and collagen-induced aggregation and platelet recruitment; P<0.0001) but not with differences in ADP- or TRAP-induced aggregation. Partial TX inhibition was independently associated with severe stroke (NIHSS ≥ 12) at both admission (P<0.05) and discharge (P<0.05). Among patients with fully blocked TX, those with elevated COX1-independent platelet reactivity (mean+2SD of aspirin-treated HS) were most likely to suffer severe stroke (P<0.05). Platelet-erythrocyte interactions enhanced platelet reactivity in these patients by COX1-dependent and -independent mechanisms (P<0.0001).
  
  
  CONCLUSIONS
  TX inhibition by aspirin varied across patients. Partial TX inhibition and COX1-independent platelet hyperfunction were associated with more-severe stroke.
authors.affiliation: Research Center, University Hospital La Fe, Valencia, Spain.
authors.forename: Juana
authors.initials: J
authors.lastname: Valles
authors.forename: Aida
authors.initials: A
authors.lastname: Lago
authors.forename: Antonio
authors.initials: A
authors.lastname: Moscardo
authors.forename: Jose
authors.initials: J
authors.lastname: Tembl
authors.forename: Vera
authors.initials: V
authors.lastname: Parkhutik
authors.forename: Maria T
authors.initials: MT
authors.lastname: Santos
mesh_terms: D000208:Acute Disease; D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D016022:Case-Control Studies; D051545:Cyclooxygenase 1 / Q000096:biosynthesis* / Q000097:blood; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D005260:Female; D006801:Humans; D002546:Ischemic Attack, Transient / Q000097:blood* / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D020521:Stroke / Q000097:blood* / Q000188:drug therapy* / Q000201:enzymology; D013928:Thromboxane A2 / Q000096:biosynthesis* / Q000097:blood
chemical_list: D016861:Cyclooxygenase Inhibitors; D013928:Thromboxane A2; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D001241:Aspirin
keywords: Acute stroke; Aspirin; Cyclooxygenase-1; Platelet–erythrocyte interactions; Thromboxane A(2)