Clinical Implications of Discrepancy between One-Stage Clotting and Chromogenic Factor IX Activity in Hemophilia B

David E. Schmidt; Åsa Truedsson; Annelie Strålfors; Johanne Andersen Hojbjerg; Nida Soutari; Margareta Holmström; Susanna Ranta; Anna Letelier; Annette Bowyer; Rolf Ljung; Jovan Antovic; Maria Bruzelius

doi:10.1055/a-2142-0262

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2024; 124(01): 032-039
DOI: 10.1055/a-2142-0262

Coagulation and Fibrinolysis

Clinical Implications of Discrepancy between One-Stage Clotting and Chromogenic Factor IX Activity in Hemophilia B

David E. Schmidt

¹Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden

²Paediatric Coagulation, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden

,

Åsa Truedsson

³Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden

,

Annelie Strålfors

³Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden

⁴Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

,

Johanne Andersen Hojbjerg

⁵Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark

⁶Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

,

Nida Soutari

³Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden

⁴Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

,

Margareta Holmström

⁷Coagulation Unit, Department of Hematology, Karolinska University Hospital, Stockholm, Sweden

⁸Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden

,

Susanna Ranta

¹Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden

²Paediatric Coagulation, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden

,

Anna Letelier

⁹Department of Clinical Sciences, Lund University, Lund, Sweden

,

Annette Bowyer

¹⁰Department of Coagulation, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom

,

Rolf Ljung

⁹Department of Clinical Sciences, Lund University, Lund, Sweden

,

Jovan Antovic

³Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden

⁴Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

,

Maria Bruzelius

⁴Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

⁷Coagulation Unit, Department of Hematology, Karolinska University Hospital, Stockholm, Sweden

› Institutsangaben

Abstract

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

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

Methods Single-center study including 21 genotyped and clinically characterized 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 hemophilia type by CSA. OSA displayed a more accurate description of the clinical bleeding severity, compared with CSA. A twofold 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 diluted normal plasma, 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.

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

Keywords

hemophilia B - factor IX - diagnostics - assays - genotype

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Referenzen

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