title: Lack of uniform platelet activation in patients after ischemic stroke and choice of antiplatelet therapy.
abstract: BACKGROUND
  Platelets play an important role in the natural history of ischemic stroke, and are known to be activated in the acute phase. Although aspirin reduces risks of myocardial infarction, stroke and cardiovascular death, the extent of platelet action and the effect of aspirin on platelet function in patients recovering from stroke remain unclear.
  
  
  METHODS
  We studied 120 individuals divided into three equal groups: aspirin-free patients after ischemic stroke, post-stroke patients receiving aspirin (81-650 mg/daily), and aspirin-free subjects with multiple risk factors for vascular disease. Conventional platelet aggregation induced by 5 microM ADP and 5 microM epinephrine, cartridge-based analyzers (Ultegra, and PFA-100) readings, and expression of CD31, CD41a, CD42b, GPIIb/IIIa activity, CD51/CD61, CD62p, CD63, CD107a, CD154, CD165, formation of platelet-monocyte aggregates, intact (SPAN12), and cleaved (WEDE15) PAR-1 thrombin receptors by flow cytometry were analyzed.
  
  
  RESULTS
  There were no differences between aspirin-free post-stroke patients and aspirin-free controls. Although aggregation was slightly higher, 12 out of the 14 receptor analyses, were surprisingly lower in the post-stroke cohort. Aspirin-treated patients exhibited highly significant inhibition of epinephrine-induced aggregation (p=0.0001), prolongation of the closure time (p=0.03), and reduction of the aspirin reactive units (p=0.02) measured by the Ultegra device. In addition, surface platelet expression of thrombospondin (p=0.001), GPIIb/IIIa activity (p=0.04), P-selectin (p=0.03), CD40-ligand (p=0.04), CD165 (p=0.02), the formation of the platelet-monocyte aggregates (p=0.01), and intact epitope of PAR-1 thrombin receptor (p=0.03) were significantly lower in the aspirin-treated group.
  
  
  CONCLUSIONS
  Platelets are not activated in aspirin-free patients after ischemic stroke. Platelet function is significantly inhibited in those treated with aspirin when compared with healthy subjects with risk factors for vascular disease. Bleeding complications and hemorrhagic transformations after aggressive antiplatelet regimens could be related to the decreased or normal baseline platelet characteristics in such patients. Further analysis of platelet heterogeneity and its clinical significance remains to be determined in randomized trials.
authors.affiliation: Internal Medicine, Johns Hopkins University, 7600 Osler drive, ste. 307, Baltimore, MD 21204, USA. Heartdrug@aol.com
authors.forename: Victor L
authors.initials: VL
authors.lastname: Serebruany
authors.forename: Alex I
authors.initials: AI
authors.lastname: Malinin
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Oshrine
authors.forename: David C
authors.initials: DC
authors.lastname: Sane
authors.forename: Aviv
authors.initials: A
authors.lastname: Takserman
authors.forename: Dan
authors.initials: D
authors.lastname: Atar
authors.forename: Charles H
authors.initials: CH
authors.lastname: Hennekens
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000187:drug effects; D001241:Aspirin / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D019013:CD40 Antigens / Q000187:drug effects; D015331:Cohort Studies; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010979:Platelet Function Tests; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000187:drug effects; D018179:Receptors, Thrombin / Q000187:drug effects; D020521:Stroke / Q000097:blood* / Q000188:drug therapy*; D019699:Thrombospondins / Q000187:drug effects
chemical_list: D015703:Antigens, CD; D019013:CD40 Antigens; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D018179:Receptors, Thrombin; D019699:Thrombospondins; D001241:Aspirin; D004837:Epinephrine