title: Platelet activation increases with the severity of peripheral arterial disease: implications for clinical management.
abstract: BACKGROUND
  Patients with peripheral arterial disease (PAD) have increased mortality from cardiovascular events compared with age and sex matched controls Platelets play a major role in atherosclerosis and thrombotic vascular events. Platelet reactivity is increased in patients with PAD compared with healthy controls. We aimed to determine the relationship, if any, between platelet activation and severity of disease.
  
  
  RESULTS
  One hundred eighty-two patients with intermittent claudication (IC) or subcritical limb ischemia (SLI), defined as the presence of rest pain or ulceration, had the following investigations performed: platelet P-selectin expression and bound fibrinogen by flow cytometric analysis and platelet aggregation using the rapid platelet function assay with arachidonic acid (AA) and thrombin receptor activation peptide (TRAP) as agonists. Patients with SLI compared with IC had significantly enhanced ADP stimulated P-selectin expression (median 42.45% [inter-quartile range 33.32% to 58.5%] vs 35.2% [26.07% to 46.32%], P = .002) and bound fibrinogen (73.7% [54.3% to 83.2%] vs 63.7% [43.8% to 76.5%], P = .001). TRAP stimulated aggregation was higher (207 [153 to 238] PAU vs 183[155 to 199] PAU, P = .04) but AA mediated aggregation was not significantly different. An ankle-brachial pressure index (ABPI) of less than 0.6 was associated with increased ADP stimulated P-selectin and bound fibrinogen (P < .05). ABPI correlated inversely with ADP stimulated P-selectin expression (r = -0.228, P = .003), ADP stimulated fibrinogen binding (r = -0.156, P = .043) and TRAP stimulated aggregation (r = -0.179, P = .04).
  
  
  CONCLUSIONS
  We have demonstrated for the first time that progression of severity of PAD is not only reflected by symptoms, signs, and ABPI but also by increased platelet activity as assessed by both flow cytometry and aggregation. As patients with more severe PAD have increased cardiovascular mortality, our findings suggest that new strategies for platelet inhibitory therapy are indicated in these patients.
authors.affiliation: Vascular Unit, University of Aberdeen, Foresterhill, United Kingdom.
authors.forename: Sriram
authors.initials: S
authors.lastname: Rajagopalan
authors.forename: Ian
authors.initials: I
authors.lastname: Mckay
authors.forename: Isobel
authors.initials: I
authors.lastname: Ford
authors.forename: Paul
authors.initials: P
authors.lastname: Bachoo
authors.forename: Michael
authors.initials: M
authors.lastname: Greaves
authors.forename: Julie
authors.initials: J
authors.lastname: Brittenden
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016718:Arachidonic Acid; D001792:Blood Platelets / Q000378:metabolism; D001794:Blood Pressure; D018450:Disease Progression; D005260:Female; D005340:Fibrinogen / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007383:Intermittent Claudication / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000096:biosynthesis* / Q000187:drug effects; D010446:Peptide Fragments; D015539:Platelet Activation / Q000502:physiology*; D011379:Prognosis; D011956:Receptors, Cell Surface; D012720:Severity of Illness Index