title: Resistance to aspirin in vitro is associated with increased platelet sensitivity to adenosine diphosphate.
abstract: BACKGROUND
  Platelet activation plays an important role in arterial thrombosis and the widespread use of aspirin has reduced major events by 25% in the secondary prevention of cardiovascular diseases. However, it appears that aspirin antiplatelet effect is not uniform and 8-45% of the population are, in vitro, aspirin resistant, and it is well recognized that platelets can be activated by pathways that are not blocked by aspirin, such as adenosine diphosphate (ADP).
  
  
  OBJECTIVE
  To investigate whether aspirin-resistant patients have a modified sensitivity to ADP-induced platelet activation
  
  
  METHODS
  Seventy-two patients were enrolled. Platelet function was measured by the PFA-100(R) analyser; platelet GP IIb-IIIa activation by ADP 10 micro M was assessed by flow cytometry using PAC-1 MoAb.
  
  
  RESULTS
  Using a collagen/epinephrine coated cartridge on the PFA-100(R), the prevalence of aspirin resistance was 29.2% (n=21). For aspirin-resistant patients, the collagen/ADP coated cartridge showed a closure time significantly shorter (p=0.004) compared to the sensitive and control groups. Platelets from aspirin-resistant patients bound PAC-1 significantly more (p=0.03) than the aspirin-sensitive patients and controls when activated with 10 micro M ADP.
  
  
  CONCLUSIONS
  Platelets from aspirin-resistant patients appear to be more sensitive and activable by ADP. This hypersensitivity could provide a possible explanation for the so-called aspirin resistance, and this could justify therapeutic improvement with alternative antiplatelet agents.
authors.affiliation: Laboratoire d'Hématologie et des Maladies du Sang, Hôpital La Miletrie, 86 000, Poitiers, France. l.macchi@chu-poitiers.fr
authors.forename: L
authors.initials: L
authors.lastname: Macchi
authors.forename: L
authors.initials: L
authors.lastname: Christiaens
authors.forename: S
authors.initials: S
authors.lastname: Brabant
authors.forename: N
authors.initials: N
authors.lastname: Sorel
authors.forename: J
authors.initials: J
authors.lastname: Allal
authors.forename: G
authors.initials: G
authors.lastname: Mauco
authors.forename: A
authors.initials: A
authors.lastname: Brizard
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000368:Aged; D000787:Angina Pectoris / Q000097:blood; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood; D004351:Drug Resistance; D054641:Dual Specificity Phosphatase 2; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects; D010979:Platelet Function Tests; D054648:Protein Phosphatase 2; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism
chemical_list: D000244:Adenosine Diphosphate; D054648:Protein Phosphatase 2; C517032:DUSP2 protein, human; D054641:Dual Specificity Phosphatase 2; D017027:Protein Tyrosine Phosphatases; D001241:Aspirin