title: Variability in platelet dense granule adenosine triphosphate release findings amongst patients tested multiple times as part of an assessment for a bleeding disorder.
abstract: BACKGROUND
  Lumi-aggregometry quantification of platelet dense granule adenosine triphosphate (ATP) release is commonly used for diagnosing platelet function disorders. As the test findings show considerable variability for healthy controls, we postulated that patient findings might also be variable and investigated patients who were assessed for dense granule ATP release defects more than once.
  
  
  METHODS
  Analyses were performed on prospectively collected data for first and second tests for subjects tested for dense granule ATP release defects more than once by the Hamilton Regional Laboratory Program (HRLMP) between January 2007 and June 2013 (cohort I). Similar analyses were performed for subjects who were recruited to a platelet disorder study (cohort II) and were assessed for ATP release defects more than once before October 2015.
  
  
  RESULTS
  A total of 150 unique subjects had multiple ATP release tests. Results with individual agonists were variable for many subjects. While normal findings with all tested agonists were often confirmed by the second test (cohort I: 83%; cohort II: 100%), impaired release with multiple agonists was confirmed in only some subjects (cohort I: 34%; cohort II: 54%). Inconsistent findings were common (cohort I: 36%; cohort II: 39%). ISTH bleeding scores showed no relationship to the test findings. The finding of impaired ATP release with 2 or more agonists on both tests was not associated with an increased likelihood of a definite bleeding disorder.
  
  
  CONCLUSIONS
  The variability in platelet dense granule ATP release findings amongst patients assessed for diagnostic purposes suggests that the test has limited value for diagnosing platelet disorders.
authors: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
authors: M S
authors: MS
authors: Badin
authors: Centre for Laboratory Medicine and Hemophilia and Hemostasis Centre, St. Gallen, Switzerland.
authors: L
authors: L
authors: Graf
authors: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
authors: J K
authors: JK
authors: Iyer
authors: Department of Medicine, McMaster University, Hamilton, ON, Canada.|Hamilton Regional Laboratory Medicine Program, Hamilton, ON, Canada.
authors: K A
authors: KA
authors: Moffat
authors: Hamilton Regional Laboratory Medicine Program, Hamilton, ON, Canada.
authors: J L
authors: JL
authors: Seecharan
authors: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.|Department of Medicine, McMaster University, Hamilton, ON, Canada.|Hamilton Regional Laboratory Medicine Program, Hamilton, ON, Canada.
authors: C P M
authors: CP
authors: Hayward
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D001778:Blood Coagulation Disorders / Q000175:diagnosis*; D001791:Blood Platelet Disorders / Q000175:diagnosis*; D015331:Cohort Studies; D006470:Hemorrhage; D006801:Humans; D010979:Platelet Function Tests / Q000379:methods* / Q000592:standards; D011446:Prospective Studies
chemical_list: D000255:Adenosine Triphosphate
keywords: Platelet; dense granule; lumi-aggregometry; secretion; variability