title: Calibrated automated thrombography demonstrates hypercoagulability in patients with idiopathic pulmonary arterial hypertension.
abstract: BACKGROUND
  Pathogenesis of idiopathic pulmonary arterial hypertension (iPAH) includes endothelial dysfunction and in situ thrombosis. A hypercoagulable state has also been postulated but never demonstrated. Our objective was to determine whether patients with iPAH had a hypercoagulable state using calibrated automated thrombography (CAT), a new tool to phenotype coagulation in vitro.
  
  
  METHODS
  16 patients with iPAH and 29 controls were studied. In vitro platelet dependent coagulation phenotyping by CAT monitored the activity of thrombin generation over time. Plasma levels of soluble thrombomodulin, tissue factor pathway inhibitor (TFPI) and von Willebrand factor (VWF) were measured as endothelial biomarkers.
  
  
  RESULTS
  Endogenous thrombin potential (ETP) in the absence of activated protein C (APC) tended to be increased in patients compared to controls (1769 versus 1656 nM.min; p=0.053). ETP was higher in the presence of APC 25 nM (ETP-APC) in patients (781 versus 494 nM.min; p=0.005). Five patients had ETP-APC higher than the 95th centile of controls. Other CAT parameters (lag time, peak thrombin and time to peak) were all consistent with some degree of hypercoagulability in patients. Regarding endothelial plasma biomarkers sTM was lower (28.4 versus 40.6 μg/l, p=0.0108) in patients; TFPI antigen and activity (respectively: 14.3 versus 10.5 μg/l, p=0.0167; 1.155 versus 1.070, p=0.0021) and VWF (1300 versus 976%, p=0.0108) were higher in patients.
  
  
  CONCLUSIONS
  We have demonstrated that at least some patients with iPAH have a hypercoagulable phenotype.
authors.affiliation: INSERM, U961, Vandoeuvre-les-Nancy, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Tournier
authors.forename: Denis
authors.initials: D
authors.lastname: Wahl
authors.forename: Ari
authors.initials: A
authors.lastname: Chaouat
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Max
authors.forename: Véronique
authors.initials: V
authors.lastname: Regnault
authors.forename: Thomas
authors.initials: T
authors.lastname: Lecompte
authors.forename: François
authors.initials: F
authors.lastname: Chabot
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001331:Automation; D001780:Blood Coagulation Tests / Q000379:methods* / Q000592:standards; D002138:Calibration; D016022:Case-Control Studies; D004727:Endothelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011651:Pulmonary Artery / Q000378:metabolism / Q000473:pathology; D019851:Thrombophilia / Q000097:blood / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D055815:Young Adult