Factor XIII--an under diagnosed deficiency--are we using the right assays?

J Thromb Haemost. 2010 Nov;8(11):2478-82. doi: 10.1111/j.1538-7836.2010.04028.x.

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).

Patients/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.

MeSH terms

  • Adult
  • Automation
  • Chemistry, Clinical / methods*
  • Child
  • Cohort Studies
  • Factor XIII / analysis*
  • Factor XIII Deficiency / blood*
  • Factor XIII Deficiency / diagnosis*
  • Heterozygote
  • Humans
  • Immune System
  • Intensive Care Units
  • Nephelometry and Turbidimetry / methods
  • Prevalence
  • Reproducibility of Results
  • Wound Healing

Substances

  • Factor XIII