title: Simultaneous thrombin and plasmin generation capacities in normal and abnormal states of coagulation and fibrinolysis in children and adults.
abstract: BACKGROUND
  Thrombin and plasmin are the key enzymes involved in coagulation and fibrinolysis, respectively. Plasma coagulative and fibrinolytic potentials in normal children and adults, and in representative pathologically altered hemostatic states, were evaluated via simultaneous assessment of thrombin and plasmin generation.
  
  
  METHODS
  An assay of Simultaneous Thrombin and Plasmin generation (STP) was developed to measure thrombin and plasmin in plasma using individual fluorometric substrates. Coagulation is initiated with dilute tissue factor, phospholipid, and calcium in platelet-poor plasma; fibrinolysis is accelerated via tissue plasminogen activator (tPA). Abnormal states of hemostasis were investigated.
  
  
  RESULTS
  STP assay reproducibility and normal adult and pediatric values for measured and calculated parameters have been established. Onset of both thrombin and plasmin generation was significantly delayed in children relative to adults (p<0.001) and the maximum amplitudes of thrombin and plasmin generation were less in children than adults (p<0.01). No significant differences were measured among pediatric age groups. The most profound impairments in thrombin generation were observed for extrinsic and common pathway factor deficiencies, with the exception of afibrinogenemia. Plasmin generation was severely impaired in deficiencies of fibrinogen and plasminogen as well as with decreased tPA reagent concentration and addition of aminocaproic acid. Plasmin generation was greatly enhanced by alpha-2-antiplasmin deficiency and excess tPA reagent.
  
  
  CONCLUSIONS
  Simultaneous assessment of thrombin and plasmin generation in plasma shows promise for affording an enhanced understanding of overall coagulative and fibrinolytic functions in physiological and pathologically altered states of hemostasis in children and adults.
authors.affiliation: Rush University Medical Center, Department of Pediatrics, Section of Hematology / Oncology, Chicago, IL 60612, USA. mgrunzke1@gmail.com
authors.forename: Mindy L
authors.initials: ML
authors.lastname: Simpson
authors.forename: Neil A
authors.initials: NA
authors.lastname: Goldenberg
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Jacobson
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Bombardier
authors.forename: William E
authors.initials: WE
authors.lastname: Hathaway
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Manco-Johnson
mesh_terms: D000328:Adult; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D002648:Child; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis; D006801:Humans; D013917:Thrombin / Q000378:metabolism
chemical_list: D013917:Thrombin; D005341:Fibrinolysin