title: Explaining and reducing the variation in inter-laboratory reported values for International Normalised Ratio.
abstract: BACKGROUND
  Monitoring of vitamin K antagonist (VKA) therapy is usually achieved using the International Normalised Ratio (INR). However, despite international standardisation, there remains considerable concern regarding ongoing high levels of inter-laboratory variation, as generated by different laboratories using the same homogeneous plasma sample. Notably, significant discrepancies continue to be evidenced in external quality assessment (EQA) environments, prompting additional investigations to determine causes and to identify potential inconsistencies of practice.
  
  
  METHODS
  Several investigations involving all 580 participants in the Haemostasis program of the RCPAQAP Haematology were undertaken from 2009 to 2016, gathering details of methodology, and comparative assessments of INR values differentially obtained directly from participants versus values calculated using raw data for PT, ISI and MNPT provided by the same participants.
  
  
  RESULTS
  Up to 6% of laboratories reported substantially different INR results compared to results calculated using differentially provided ISI, MNPT and PT data in 6 out of 8 surveys in 2009, highlighting discrepancies in ISI and MNPT values reported vs used by laboratories. Subsequent highlighting of issues to laboratories led to significant improvements in later surveys, with <1% of laboratories yielding different values in 2012, 2013 and 2016.
  
  
  CONCLUSIONS
  Our study identified that pre- or post- analytical errors explained a large proportion of inter-laboratory variation in INR. These errors can lead to serious clinical consequences if such data discrepancies are applied to patients, with incorrectly reported INRs potentially leading to altered warfarin therapy. Further education in the importance of the INR process appears warranted.
authors.affiliation: RCPAQAP Haematology, Suite 201, Level 2, 8 Herbert St, St Leonards, Australia. Electronic address: Roslyn.Bonar@rcpaqap.com.au.
authors.forename: Roslyn
authors.initials: R
authors.lastname: Bonar
authors.affiliation: Sydney Centres for Thrombosis and Haemostasis, Department of Haematology, Institute of Clinical Pathology and Medical Research, Pathology West, NSW Health Pathology, Westmead Hospital, Sydney, Australia. Electronic address: emmanuel.favaloro@health.nsw.gov.au.
authors.forename: Emmanuel J
authors.initials: EJ
authors.lastname: Favaloro
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D016903:Drug Monitoring / Q000379:methods / Q000592:standards; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D019934:International Normalized Ratio / Q000379:methods / Q000592:standards; D059021:Laboratory Proficiency Testing / Q000379:methods / Q000592:standards; D012016:Reference Values; D011795:Surveys and Questionnaires; D014812:Vitamin K / Q000037:antagonists & inhibitors
chemical_list: D000925:Anticoagulants; D014812:Vitamin K
keywords: Anticoagulant therapy; External quality assurance; International normalised ratio; Post-analytical error; Pre-analytical error