title: Large external quality assessment survey on thrombin generation with CAT: further evidence for the usefulness of normalisation with an external reference plasma.
abstract: BACKGROUND
  Calibrated Automated Thrombography (CAT) has been widely used to assess in vitro thrombin generation as an informative intermediary phenotype of coagulation. Interlaboratory exercises have documented a worrisome poor reproducibility. There are some data on the normalisation with an appropriate external reference plasma (RP). This multicentre study of the French-speaking CAT Club aimed at providing further evidence for the usefulness of such a normalisation.
  
  
  METHODS
  Lyophilised aliquots of a RP along with 3 plasmas (P1=normal; P2=hypo-; P3=hypercoagulable) were sent to 34 laboratories (corresponding to 38 instruments). CAT was studied using 1 and 5 pM tissue factor and other dedicated reagents. Normalisation with the local RP in use in the laboratory could also be performed. Interlaboratory CVs were calculated for each plasma before and after normalisation.
  
  
  RESULTS
  Regarding endogenous thrombin potential, a good discrimination between the 3 plasmas was achieved in all laboratories but there was no overlap after normalisation only. CVs were generally not reduced with the use of local RP but were generally improved with normalisation using the external RP, often becoming lower than 10%. Regarding P2 however, the benefit of normalisation was poor, and there were analytical difficulties as well, some laboratories being unable to get a useable signal.
  
  
  CONCLUSIONS
  We confirm that normalisation of CAT results with a suitable external RP is useful in "real life" practice as it often permits an acceptable level of interlaboratory variability. In case of frank hypocoagulability, further improvements are required to get reliable, potentially clinically relevant results.
authors.affiliation: Hématologie biologique - Hémostase, CHU Nancy, Nancy, France; INSERM U 1116, Groupe Choc, Equipe 2, 54511 Vandoeuvre les Nancy, France. Electronic address: julien.perrin@chu-nancy.fr.
authors.forename: Julien
authors.initials: J
authors.lastname: Perrin
authors.affiliation: Diagnostica Stago, Asnières, France.
authors.forename: François
authors.initials: F
authors.lastname: Depasse
authors.affiliation: Service d'hématologie, Hôpitaux Universitaires de Genève (HUG), Genève, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lecompte
mesh_terms: D001780:Blood Coagulation Tests / Q000379:methods* / Q000592:standards; D002138:Calibration; D006801:Humans; D010949:Plasma / Q000378:metabolism*; D012015:Reference Standards; D015203:Reproducibility of Results; D013917:Thrombin / Q000378:metabolism*
chemical_list: D013917:Thrombin
keywords: Normalisation; Reference plasma; Standardisation; Thrombin generation tests