title: The factor VIII inhibitor assays can be standardized: results of a workshop.
abstract: BACKGROUND
  The Bethesda and the Nijmegen assays are commonly used for the measurement of inhibitor levels in hemophilia A patients. Despite test innovations, the between-laboratory coefficient of variation (CVb) of factor VIII inhibitor test data in external quality surveys remains very high (40-60%) with a high degree of false-negative and false-positive results resulting in undesired effects on treatment.
  
  
  OBJECTIVE
  Organization of a workshop in order to address the causes of this phenomenon and to suggest ways to improve the assays.
  
  
  METHODS
  Fifteen laboratories showing a high CVb in regular surveys and using a variety of methods participated in the wet workshop, which included four different sessions where variables probably contributing to the high CVb (e.g. use of [non-]buffered plasma, FVIII-deficient plasma, sample dilution and APTT reagents) were investigated.
  
  
  RESULTS
  The CVb varied from 30% to 70% in the first session of the workshop when the participants used their own test settings and reagents. The use of buffered normal pooled plasma and FVIII-deficient plasma as a reference sample by all participants did not significantly alter the CVb (35-50%) but decreased the number of false positives. However, the use of buffered pooled plasma in combination with standardized sample dilution procedures by all participants showed a significant improvement (CVb, 10-20%).
  
  
  CONCLUSIONS
  These results may contribute to improvement of FVIII inhibitor testing. However, improved inter-laboratory comparison of factor VIII inhibitor assay results can only be reached when further local standardization is implemented.
authors.affiliation: ECAT Foundation, Leiden, the Netherlands. bertverbruggennijmegen@gmail.com
authors.forename: B
authors.initials: B
authors.lastname: Verbruggen
authors.forename: M
authors.initials: M
authors.lastname: Dardikh
authors.forename: R
authors.initials: R
authors.lastname: Polenewen
authors.forename: C
authors.initials: C
authors.lastname: van Duren
authors.forename: P
authors.initials: P
authors.lastname: Meijer
mesh_terms: D001780:Blood Coagulation Tests; D005169:Factor VIII / Q000037:antagonists & inhibitors*; D006801:Humans; D015203:Reproducibility of Results
chemical_list: D005169:Factor VIII