title: Calibrated automated thrombin generation and modified thromboelastometry in haemophilia A.
abstract: BACKGROUND
  Global coagulation tests may have a better relation with phenotype in haemophilia than traditional coagulation tests. These include the Calibrated Automated Thrombin generation assay (CAT) and modified thromboelastometry using low tissue factor triggering. Both have shown marked variability in thrombin generation and clot formation profiles respectively despite similar FVIII:C levels and have been suggested as means to monitor treatment. Data with modified thromboelastometry are largely limited to severe and moderate haemophiliacs. CAT measurements in haemophilia are generally performed at low TF concentrations (1 pM) because of a higher sensitivity for the intrinsic pathway at this concentration but is also sensitive for FVIII at higher concentrations (5 pM) and this has the advantage that inhibition of contact factor activation can be avoided. No formal comparison of both TF concentrations has been reported and the data on modified thromboelastometry in mild haemophilia are limited.
  
  
  METHODS
  In this study we compared thrombin generation at 1 and 5 pM in 57 haemophilia patients without exposure to treatment and 41 patients after treatment. We also assessed the sensitivity of thromboelastometry for haemophilia A in 29 patients.
  
  
  CONCLUSIONS
  We found that CAT discriminates well between normal individuals and haemophilia patients; also FVIII:C correlates well with the ETP/peak. We found no clear advantages of measurements at 1 compared to 5 pM but found increased variation over time at 1 pM. The sensitivity of modified thromboelastometry for haemophilia A was less than CAT with abnormal measurements largely limited to severe and moderate patients. Larger studies correlating both methods with clinical outcome are required.
authors.affiliation: Sheffield Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, United Kingdom. joost.vanveen@ukgateway.net
authors.forename: Joost J
authors.initials: JJ
authors.lastname: van Veen
authors.forename: Alex
authors.initials: A
authors.lastname: Gatt
authors.forename: Annette E
authors.initials: AE
authors.lastname: Bowyer
authors.forename: Peter C
authors.initials: PC
authors.lastname: Cooper
authors.forename: Steve
authors.initials: S
authors.lastname: Kitchen
authors.forename: Mike
authors.initials: M
authors.lastname: Makris
mesh_terms: D001780:Blood Coagulation Tests / Q000379:methods* / Q000706:statistics & numerical data; D016022:Case-Control Studies; D005169:Factor VIII / Q000627:therapeutic use; D006467:Hemophilia A / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D008297:Male; D012016:Reference Values; D013916:Thrombelastography / Q000379:methods* / Q000706:statistics & numerical data; D013917:Thrombin / Q000096:biosynthesis*
chemical_list: D005169:Factor VIII; D013917:Thrombin