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

A. S. Lawrie, L. Green, I. J. Mackie, R. Liesner, S. J. Machin, F. Peyvandi

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

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 (R2 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.

Original languageEnglish
Pages (from-to)2478-2482
Number of pages5
JournalJournal of Thrombosis and Haemostasis
Volume8
Issue number11
DOIs
Publication statusPublished - Nov 2010

Fingerprint

Factor XIII
Ammonia
Factor XIII Deficiency
Iodoacetamide
Pediatric Intensive Care Units
Solubility
Enzyme-Linked Immunosorbent Assay
Pediatrics

Keywords

  • Acquired FXIII deficiency
  • Factor XIII
  • Factor XIII deficiency
  • FXIII assay

ASJC Scopus subject areas

  • Hematology

Cite this

Factor XIII - an under diagnosed deficiency - are we using the right assays? / Lawrie, A. S.; Green, L.; Mackie, I. J.; Liesner, R.; Machin, S. J.; Peyvandi, F.

In: Journal of Thrombosis and Haemostasis, Vol. 8, No. 11, 11.2010, p. 2478-2482.

Research output: Contribution to journalArticle

Lawrie, A. S. ; Green, L. ; Mackie, I. J. ; Liesner, R. ; Machin, S. J. ; Peyvandi, F. / Factor XIII - an under diagnosed deficiency - are we using the right assays?. In: Journal of Thrombosis and Haemostasis. 2010 ; Vol. 8, No. 11. pp. 2478-2482.
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abstract = "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 (R2 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.",
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