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

Summary.  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.