title: Factor XIII--an under diagnosed deficiency--are we using the right assays?
abstract: BACKGROUND
  The clot solubility test is the most widely used method for detection of factor (F)XIII deficiency. However, it will only detect severe deficiencies; consequently mild deficiencies and heterozygous states are probably under diagnosed.
  
  
  OBJECTIVE
  As an alternative first-line screening test, we assessed an automated quantitative ammonia release assay (QARA).
  
  
  METHODS
  Inter-assay imprecision was evaluated with commercial normal and pathological control plasmas (10 replicates on each of 5 days). Using the QARA and other commercial assays a comparative assessment of congenital (FXIII range < 1-70 u dL(-1), n = 9) and acquired (n = 43) deficiencies was made. We also investigated the prevalence of acquired deficiencies in hospitalized patients using residual samples from adult patients (n = 1004) and from a paediatric intensive care unit (ICU, n = 56).
  
  
  RESULTS
  Assay imprecision was acceptably low (normal control: mean 86.6 u dL(-1); cv = 2.0%; pathological control: mean 27.5 u dL(-1); cv = 3.8%). Using an iodoacetamide blanking procedure, the QARA results (FXIII range < 1-70 u dL(-1)) exhibited close agreement with those from an immuno-turbidometric FXIII A-subunit (FXIII-A) method. There was also good correlation (R(2) ≥ 0.89) between the QARA (range 20-180 u dL(-1)), a second chromogenic assay, the FXIII-A and FXIII A+B-subunit ELISA. We found that 21% of samples from adult patients had FXIII levels < 70 u dL(-1) (mean normal ± 2 SD 73-161 u dL(-1)) with 6% < 50 u dL(-1). Within the paediatric ICU samples, 52% were < 70 u dL(-1), with 21% < 50 u dL(-1).
  
  
  CONCLUSIONS
  Our data demonstrates that the automated assay is sensitive, highly reproducible and the results from clinical samples suggest that acquired FXIII deficiency is a relatively common phenomenon in hospital patients after surgery and in ICU.
authors: Haemostasis Research Unit, Department of Haematology, University College London, London, UK. andrew.lawrie@ucl.ac.uk
authors: A S
authors: AS
authors: Lawrie
authors: L
authors: L
authors: Green
authors: I J
authors: IJ
authors: Mackie
authors: R
authors: R
authors: Liesner
authors: S J
authors: SJ
authors: Machin
authors: F
authors: F
authors: Peyvandi
mesh_terms: D000328:Adult; D001331:Automation; D002624:Chemistry, Clinical / Q000379:methods*; D002648:Child; D015331:Cohort Studies; D005176:Factor XIII / Q000032:analysis*; D005177:Factor XIII Deficiency / Q000097:blood* / Q000175:diagnosis*; D006579:Heterozygote; D006801:Humans; D007107:Immune System; D007362:Intensive Care Units; D009391:Nephelometry and Turbidimetry / Q000379:methods; D015995:Prevalence; D015203:Reproducibility of Results; D014945:Wound Healing
chemical_list: D005176:Factor XIII