title: Time to think outside the box? Prothrombin time, international normalised ratio, international sensitivity index, mean normal prothrombin time and measurement of uncertainty: a novel approach to standardisation.
abstract: BACKGROUND
  The prothrombin time (PT) assay is the most clinically ordered coagulation test, and most often used for monitoring of vitamin K antagonist therapy (e.g., warfarin), where results are expressed as an international normalised ratio (INR). The INR is in essence the patient's PT 'mathematically adjusted' to a standardised value taking into account the peculiarities of the test system as defined by an ISI (international sensitivity index) and MNPT (mean normal prothrombin time). Although some manufacturers provide assigned ISI values for specific PT reagents and instrumentation, it is still recommended practice that laboratories check or validate these ISIs, as well as estimate the MNPT. Where an ISI is not provided by a manufacturer, the laboratory needs to estimate its own value. Current recommendations suggest the use of commercial reference-plasma calibration sets, but there is limited information on the performance of these in the field.
  
  
  RESULTS
  We report a comparative study that assessed the utility of three such commercial calibration plasma sets, used as recommended, as well as alternate or supplementary procedures for estimation of ISI and MNPT. The latter included one novel approach using comparative data of 'existing' versus 'replacement' reagent, as well as assessment of external quality assurance data. Although MNPT value estimates were not grossly disparate, a wide variety of ISI values (e.g., 1.12-1.30 for our primary instrument) was obtained with the different plasma sets.
  
  
  CONCLUSIONS
  Because of the above, further verification checks are required prior to acceptance of ISI and MNPT estimates generated from commercial plasma calibration sets. We also provide some recommendations regarding the process of standardisation of INR testing.
authors.affiliation: Department of Haematology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, New South Wales, Australia. emmanuel.favaloro@swahs.health.nsw.gov.au
authors.forename: Emmanuel J
authors.initials: EJ
authors.lastname: Favaloro
authors.forename: Sayed
authors.initials: S
authors.lastname: Hamdam
authors.forename: Jane
authors.initials: J
authors.lastname: McDonald
authors.forename: Wendy
authors.initials: W
authors.lastname: McVicker
authors.forename: Violeta
authors.initials: V
authors.lastname: Ule
mesh_terms: D002138:Calibration; D006801:Humans; D019934:International Normalized Ratio / Q000295:instrumentation / Q000379:methods / Q000592:standards*; D011517:Prothrombin Time / Q000295:instrumentation / Q000379:methods / Q000592:standards*; D011933:Reagent Kits, Diagnostic / Q000592:standards*; D012015:Reference Standards
chemical_list: D011933:Reagent Kits, Diagnostic