title: Viscoelastic measurements of platelet function, not fibrinogen function, predicts sensitivity to tissue-type plasminogen activator in trauma patients.
abstract: BACKGROUND
  Systemic hyperfibrinolysis is a lethal phenotype of trauma-induced coagulopathy. Its pathogenesis is poorly understood. Recent studies have support a central role of platelets in hemostasis and in fibrinolysis regulation, implying that platelet impairment is integral to the development of postinjury systemic hyperfibrinolysis.
  
  
  OBJECTIVE
  The objective of this study was to identify if platelet function is associated with blood clot sensitivity to fibrinolysis. We hypothesize that platelet impairment of the ADP pathway correlates with fibrinolysis sensitivity in trauma patients.
  
  
  METHODS
  A prospective observational study of patients meeting the criteria for the highest level of activation at an urban trauma center was performed. Viscoelastic parameters associated with platelet function (maximum amplitude [MA]) were measured with native thrombelastography (TEG), and TEG platelet mapping of the ADP pathway (ADP-MA). The contribution of fibrinogen to clotting was measured with TEG (angle) and the TEG functional fibrinogen (FF) assay (FF-MA). Another TEG assay containing tissue-type plasminogen activator (t-PA) (75 ng mL(-1) ) was used to assess clot sensitivity to an exogenous fibrinolytic stimulus by use of the TEG lysis at 30 min (LY30) variable. Multivariate linear regression was used to identify which TEG variable correlated with t-PA-LY30 (quantification of fibrinolysis sensitivity).
  
  
  RESULTS
  Fifty-eight trauma patients were included in the analysis, with a median injury severity score of 17 and a base deficit of 6 mEq L(-1) . TEG parameters that significantly predicted t-PA-LY30 were related to platelet function (ADP-MA, P = 0.001; MA, P < 0.001) but not to fibrinogen (FF-MA, P = 0.773; angle, P = 0.083). Clinical predictors of platelet ADP impairment included calcium level (P = 0.001), base deficit (P = 0.001), and injury severity (P = 0.001).
  
  
  CONCLUSIONS
  Platelet impairment of the ADP pathway is associated with increased sensitivity to t-PA. ADP pathway inhibition in platelets may be an early step in the pathogenesis of systemic hyperfibrinolysis.
authors.affiliation: Department of Surgery, University of Colorado, Aurora, CO, USA.|Denver Health Medical Center, Denver, CO, USA.
authors.forename: H B
authors.initials: HB
authors.lastname: Moore
authors.affiliation: Department of Surgery, University of Colorado, Aurora, CO, USA.|Denver Health Medical Center, Denver, CO, USA.
authors.forename: E E
authors.initials: EE
authors.lastname: Moore
authors.affiliation: Department of Surgery, University of Colorado, Aurora, CO, USA.|Denver Health Medical Center, Denver, CO, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Chapman
authors.affiliation: Department of Surgery, University of Colorado, Aurora, CO, USA.|Denver Health Medical Center, Denver, CO, USA.
authors.forename: E
authors.initials: E
authors.lastname: Gonzalez
authors.affiliation: Department of Surgery, University of Colorado, Aurora, CO, USA.|Denver Health Medical Center, Denver, CO, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Slaughter
authors.affiliation: Department of Surgery, University of Colorado, Aurora, CO, USA.|Denver Health Medical Center, Denver, CO, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Morton
authors.affiliation: Department of Surgery, University of Colorado, Aurora, CO, USA.
authors.forename: A
authors.initials: A
authors.lastname: D'Alessandro
authors.affiliation: Department of Surgery, University of Colorado, Aurora, CO, USA.
authors.forename: K C
authors.initials: KC
authors.lastname: Hansen
authors.affiliation: Department of Surgery, University of Colorado, Aurora, CO, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sauaia
authors.affiliation: Department of Surgery, University of Colorado, Aurora, CO, USA.
authors.forename: A
authors.initials: A
authors.lastname: Banerjee
authors.affiliation: Department of Surgery, University of Colorado, Aurora, CO, USA.|Bonfils Blood Center, Denver, CO, USA.
authors.forename: C C
authors.initials: CC
authors.lastname: Silliman
mesh_terms: D000244:Adenosine Diphosphate / Q000097:blood; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D001809:Blood Viscosity; D002118:Calcium / Q000097:blood; D004548:Elasticity; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D005342:Fibrinolysis / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D015601:Injury Severity Score; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018579:Patient Selection; D010979:Platelet Function Tests; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015912:Thrombolytic Therapy / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome; D014947:Wounds and Injuries / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: D015415:Biomarkers; D005343:Fibrinolytic Agents; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D010959:Tissue Plasminogen Activator; D002118:Calcium
keywords: blood platelet disorder; fibrinogen; fibrinolysis; platelet function tests; trauma