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Discrepancies between the one-stage clotting assay and the chromogenic assay in haemophilia B

Kihlberg, K. LU ; Strandberg, K. LU ; Rosén, S.; Ljung, R. LU and Astermark, J. LU (2017) In Haemophilia
Abstract

Introduction: Assay discrepancy in factor VIII activity between the one-stage and the chromogenic assays has been described in approximately one third of patients with non-severe haemophilia A. Whether assay discrepancy may also occur in patients with haemophilia B remains unknown. Aim: This study compared the results from the one-stage and the chromogenic assays in patients with haemophilia B. Methods: Plasma samples from patients with haemophilia B attending the haemophilia centre in Malmö, Sweden, were collected after a wash-out period of more than 7 days and analysed with both assays. Results: Fifty samples from 36 patients were analysed. No discrepancy was found in patients with severe haemophilia B. Among the 44 plasma samples... (More)

Introduction: Assay discrepancy in factor VIII activity between the one-stage and the chromogenic assays has been described in approximately one third of patients with non-severe haemophilia A. Whether assay discrepancy may also occur in patients with haemophilia B remains unknown. Aim: This study compared the results from the one-stage and the chromogenic assays in patients with haemophilia B. Methods: Plasma samples from patients with haemophilia B attending the haemophilia centre in Malmö, Sweden, were collected after a wash-out period of more than 7 days and analysed with both assays. Results: Fifty samples from 36 patients were analysed. No discrepancy was found in patients with severe haemophilia B. Among the 44 plasma samples from patients with non-severe disease, 15 showed a twofold or greater difference between the results of the two methods, with the chromogenic method presenting the higher value (mean FIX:Cone-stage 0.02 vs. FIX:Cchromo 0.06 IU mL-1). Of these 15 samples, 14 were from seven individuals from five families with the same mutated amino acid at the N-terminal cleaving site of the activation peptide (FIX: c.572G>A; p.Arg191His or FIX: c.571C>T; p.Arg191Cys). These mutations were not observed in any patients with non-discrepant results. The reported bleeding frequency for these patients was low and indicative of a mild bleeding phenotype. Conclusion: Our findings imply that assay discrepancy occurs for factor IX activity and that both type of assays are needed for a correct diagnosis and classification of haemophilia B. The underlying mechanism by which the mutation influences the assays remains to be determined.

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author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Assay discrepancy, Chromogenic assay, Coagulation factor IX, Haemophilia B, Mutations, One-stage assay
in
Haemophilia
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • scopus:85018672226
  • wos:000405873900046
ISSN
1351-8216
DOI
10.1111/hae.13219
language
English
LU publication?
yes
id
0a58a3d9-8606-4e4c-9859-5bb29ba2c8b2
date added to LUP
2017-06-01 11:34:35
date last changed
2017-09-18 11:38:33
@article{0a58a3d9-8606-4e4c-9859-5bb29ba2c8b2,
  abstract     = {<p>Introduction: Assay discrepancy in factor VIII activity between the one-stage and the chromogenic assays has been described in approximately one third of patients with non-severe haemophilia A. Whether assay discrepancy may also occur in patients with haemophilia B remains unknown. Aim: This study compared the results from the one-stage and the chromogenic assays in patients with haemophilia B. Methods: Plasma samples from patients with haemophilia B attending the haemophilia centre in Malmö, Sweden, were collected after a wash-out period of more than 7 days and analysed with both assays. Results: Fifty samples from 36 patients were analysed. No discrepancy was found in patients with severe haemophilia B. Among the 44 plasma samples from patients with non-severe disease, 15 showed a twofold or greater difference between the results of the two methods, with the chromogenic method presenting the higher value (mean FIX:C<sub>one-stage</sub> 0.02 vs. FIX:C<sub>chromo</sub> 0.06 IU mL<sup>-1</sup>). Of these 15 samples, 14 were from seven individuals from five families with the same mutated amino acid at the N-terminal cleaving site of the activation peptide (FIX: c.572G&gt;A; p.Arg191His or FIX: c.571C&gt;T; p.Arg191Cys). These mutations were not observed in any patients with non-discrepant results. The reported bleeding frequency for these patients was low and indicative of a mild bleeding phenotype. Conclusion: Our findings imply that assay discrepancy occurs for factor IX activity and that both type of assays are needed for a correct diagnosis and classification of haemophilia B. The underlying mechanism by which the mutation influences the assays remains to be determined.</p>},
  author       = {Kihlberg, K. and Strandberg, K. and Rosén, S. and Ljung, R. and Astermark, J.},
  issn         = {1351-8216},
  keyword      = {Assay discrepancy,Chromogenic assay,Coagulation factor IX,Haemophilia B,Mutations,One-stage assay},
  language     = {eng},
  month        = {04},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {Haemophilia},
  title        = {Discrepancies between the one-stage clotting assay and the chromogenic assay in haemophilia B},
  url          = {http://dx.doi.org/10.1111/hae.13219},
  year         = {2017},
}