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Clinical Implications of Discrepancy between One-stage Clotting and Chromogenic Factor IX Activity in Haemophilia B

Schmidt, David E. ; Truedsson, Asa ; Strålfors, Annelie Cecilia ; Andersen Højbjerg, Johanne ; Soutari, Nida ; Holmström, Margareta ; Ranta, Susanna ; Letelier, Anne ; Bowyer, Annette and Ljung, Rolf LU orcid , et al. (2023) In Thrombosis and Haemostasis
Abstract

BACKGROUND: Discrepancy in factor IX activity (FIX:C) between one-stage assay (OSA) and chromogenic substrate assay (CSA) in patients with haemophilia B (PwHB) introduces challenges for clinical management.

AIM: To study the differences in FIX activity using OSA and CSA in moderate and mild haemophilia B (HB), their impact on classification of severity, and correlation with genotype.

METHODS: Single-centre study including 21 genotyped and clinically characterised PwHB. FIX:C by OSA was measured using ActinFSL (Siemens) and CSA by Biophen (Hyphen). In addition, in-vitro experiments with wild-type FIX were performed. Reproducibility of CSA was assessed between three European coagulation laboratories.

RESULTS: FIX:C by... (More)

BACKGROUND: Discrepancy in factor IX activity (FIX:C) between one-stage assay (OSA) and chromogenic substrate assay (CSA) in patients with haemophilia B (PwHB) introduces challenges for clinical management.

AIM: To study the differences in FIX activity using OSA and CSA in moderate and mild haemophilia B (HB), their impact on classification of severity, and correlation with genotype.

METHODS: Single-centre study including 21 genotyped and clinically characterised PwHB. FIX:C by OSA was measured using ActinFSL (Siemens) and CSA by Biophen (Hyphen). In addition, in-vitro experiments with wild-type FIX were performed. Reproducibility of CSA was assessed between three European coagulation laboratories.

RESULTS: FIX:C by CSA was consistently lower than by OSA, with 10/17 PwHB having a more severe haemophila type by CSA. OSA displayed a more accurate description of the clinical bleeding severity, compared with CSA. A two-fold difference between OSA:CSA FIX:C was present in 12/17 PwHB; all patients had genetic missense variants in the FIX serine protease domain. Discrepancy was also observed with healthy control FIX, most significant for values below 0.10 IU/mL. Assessment of samples with low FIX:C showed excellent reproducibility of the CSA results between the laboratories.

CONCLUSIONS: FIX activity was consistently higher by OSA compared to the CSA. Assessing FIX by CSA alone would have led to diagnosis of a more severe haemophilia type in a significant proportion of patients. Our study suggests using both OSA and CSA FIX:C together with genotyping to classify haemophilia B severity and provide essential information for clinical management.

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organization
publishing date
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Contribution to journal
publication status
epub
subject
in
Thrombosis and Haemostasis
publisher
Schattauer GmbH
external identifiers
  • scopus:85167922899
  • pmid:37494968
ISSN
0340-6245
DOI
10.1055/a-2142-0262
language
English
LU publication?
yes
additional info
Thieme. All rights reserved.
id
10842e8f-8f27-402e-8b9b-fcaf3c1eabca
date added to LUP
2023-07-31 12:55:32
date last changed
2024-04-20 00:00:58
@article{10842e8f-8f27-402e-8b9b-fcaf3c1eabca,
  abstract     = {{<p>BACKGROUND: Discrepancy in factor IX activity (FIX:C) between one-stage assay (OSA) and chromogenic substrate assay (CSA) in patients with haemophilia B (PwHB) introduces challenges for clinical management.</p><p>AIM: To study the differences in FIX activity using OSA and CSA in moderate and mild haemophilia B (HB), their impact on classification of severity, and correlation with genotype.</p><p>METHODS: Single-centre study including 21 genotyped and clinically characterised PwHB. FIX:C by OSA was measured using ActinFSL (Siemens) and CSA by Biophen (Hyphen). In addition, in-vitro experiments with wild-type FIX were performed. Reproducibility of CSA was assessed between three European coagulation laboratories.</p><p>RESULTS: FIX:C by CSA was consistently lower than by OSA, with 10/17 PwHB having a more severe haemophila type by CSA. OSA displayed a more accurate description of the clinical bleeding severity, compared with CSA. A two-fold difference between OSA:CSA FIX:C was present in 12/17 PwHB; all patients had genetic missense variants in the FIX serine protease domain. Discrepancy was also observed with healthy control FIX, most significant for values below 0.10 IU/mL. Assessment of samples with low FIX:C showed excellent reproducibility of the CSA results between the laboratories.</p><p>CONCLUSIONS: FIX activity was consistently higher by OSA compared to the CSA. Assessing FIX by CSA alone would have led to diagnosis of a more severe haemophilia type in a significant proportion of patients. Our study suggests using both OSA and CSA FIX:C together with genotyping to classify haemophilia B severity and provide essential information for clinical management.</p>}},
  author       = {{Schmidt, David E. and Truedsson, Asa and Strålfors, Annelie Cecilia and Andersen Højbjerg, Johanne and Soutari, Nida and Holmström, Margareta and Ranta, Susanna and Letelier, Anne and Bowyer, Annette and Ljung, Rolf and Antovic, Jovan P and Bruzelius, Maria}},
  issn         = {{0340-6245}},
  language     = {{eng}},
  month        = {{07}},
  publisher    = {{Schattauer GmbH}},
  series       = {{Thrombosis and Haemostasis}},
  title        = {{Clinical Implications of Discrepancy between One-stage Clotting and Chromogenic Factor IX Activity in Haemophilia B}},
  url          = {{http://dx.doi.org/10.1055/a-2142-0262}},
  doi          = {{10.1055/a-2142-0262}},
  year         = {{2023}},
}