title: Impairment of the hemostatic potential of platelets during storage as evaluated by flow cytometry, thrombin generation, and thrombelastography under conditions promoting formation of coated platelets.
abstract: BACKGROUND
  The increasing demand for platelet (PLT) transfusions has focused attention on appropriate use. Coated PLTs are a subpopulation of highly procoagulant PLTs formed by simultaneous stimulation by the agonist's collagen and thrombin hypothesized to drive clot formation at the site of vascular injury. Prolonged storage of PLTs may reduce their ability to support optimal hemostasis upon transfusion.
  
  
  METHODS
  PLT concentrates (PCs) stored for 1, 4, 6, and 8 days were costimulated with thrombin and the collagen glycoprotein VI (GPVI) receptor agonist convulxin, and their ability to form coated PLTs was determined by flow cytometry. Further, a plasma-based thrombin generation assay and thrombelastography were used to evaluate the aged PCs' capacity to support thrombin generation and clot formation, respectively. The stored PCs were additionally tested by standard quality control methods.
  
  
  RESULTS
  PLT quality as measured by standard analyses was acceptable according to current practice. The hemostatic potential, however, was impaired with increasing storage time. The formation of coated PLTs decreased significantly from approximately 85 to 55 percent with increasing storage time (p<0.05). The velocity of clot formation was significantly increased from Day 4 (p<0.05). The velocity of thrombin generation and resistance against fibrinolysis were significantly reduced on Day 8 compared to Day 1 of storage (p<0.05).
  
  
  CONCLUSIONS
  Data in the present study suggest that storage significantly reduced the stored PLTs' ability to respond to conditions expected to exist at the site of vascular injury and that storage-induced reduction in PLT activation sensitivity correlated with a loss of hemostatic potential.
authors.affiliation: Hemostasis Biology, Novo Nordisk A/S, Maaloev, Denmark.
authors.forename: Mette S
authors.initials: MS
authors.lastname: Svendsen
authors.forename: Rasmus
authors.initials: R
authors.lastname: Rojkjaer
authors.forename: Annemarie T
authors.initials: AT
authors.lastname: Kristensen
authors.forename: José A
authors.initials: JA
authors.lastname: Salado-Jimena
authors.forename: Marianne
authors.initials: M
authors.lastname: Kjalke
authors.forename: Pär I
authors.initials: PI
authors.lastname: Johansson
mesh_terms: D001792:Blood Platelets / Q000166:cytology / Q000502:physiology*; D001793:Blood Preservation; D005434:Flow Cytometry; D006487:Hemostasis; D006801:Humans; D015539:Platelet Activation; D013916:Thrombelastography; D013917:Thrombin / Q000096:biosynthesis; D013997:Time Factors
chemical_list: D013917:Thrombin