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

Kihlberg, Kristina; Strandberg, Karin; Rosén, S.; Ljung, Rolf; Astermark, Jan

doi:10.1111/hae.13219

Cited by 36 publications

(43 citation statements)

References 18 publications

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“…There is also a limitation in drawing conclusions about discrepancies when a single OSA is used as a “gold standard” in view of the known variability between different OSAs related to APTT reagent differences . Kilberg and colleagues recently reported discrepancies between CSA and OSA for measurement of native FIX in a subgroup of nonsevere Haemophilia B with FIX by CSA observed to be more than twice the OSA level . They speculated that this was related to a particular causative mutation.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of chromogenic factor IX assays by automated protocols

et al. 2018

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Section: Discussionmentioning

confidence: 99%

Evaluation of chromogenic factor IX assays by automated protocols

et al. 2018

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“…Previous studies in nonsevere hemophilia A have reported an assay discrepancy prevalence of 12% to 40% . Studies in hemophilia B are scarce, with 1 study demonstrating a prevalence of 25% assay discrepancy in a nonsevere hemophilia B population …”

Section: Diagnosis Of Nonsevere Hemophiliamentioning

confidence: 95%

“…In nonsevere hemophilia B, assay discrepancy was predominantly present with higher results with the chromogenic assay . The higher chromogenic assay results were found in patients with mutations p.Arg191His and p.Arg191Cys, located at the N‐terminal cleaving site of the linker protein domain.…”

Section: Diagnosis Of Nonsevere Hemophiliamentioning

confidence: 97%

Hemophilia management: Huge impact of a tiny difference

Kloosterman

Zwagemaker

Abdi

et al. 2020

Research and Practice in Thrombosis and Haemostasis

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Hemophilia A and B are inherited X‐linked disorders of hemostasis, associated with an increased bleeding tendency. Patients with severe hemophilia have undetectable clotting factor levels and experience spontaneous bleeds. In patients with nonsevere hemophilia, the clotting factor levels are 2% to 40% of normal and bleeds predominantly occur after provocative events such as trauma and surgery. Despite this milder phenotype, patients with nonsevere hemophilia may suffer from considerable morbidity and have an increased mortality risk. However, many aspects of the course of disease and treatment remain unclear. Information on the factors influencing interindividual differences in bleeding phenotype is lacking, and misdiagnosis may occur due to assay discrepancies in the diagnostic workup. Desmopressin is the preferred treatment modality, but some patients and indications require treatment with clotting factor concentrates. This may elicit inhibitor formation, which is associated with an increased burden of disease and a higher mortality rate. It has been found that patients with nonsevere hemophilia A carry a lifelong risk for this serious complication. In this review, we provide an overview of the current knowledge of the diagnosis and management of nonsevere hemophilia. A report of science presented at the International Society on Thrombosis and Haemostasis 2019 Annual Congress is also provided.

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“…In clinical practice, FIX activity assessment is most commonly performed using the aPTT‐based one‐stage assay (OSA) and less often the chromogenic assay . However, as for haemophilia A, both assays may be needed for an accurate diagnosis and classification of disease severity . The OSA is a simple and rapid method, which is inexpensive and easily automated, and is the established European Pharmacopeia method for FIX concentrate potency labelling .…”

Section: Assessment Of Clinical Heterogeneity and Treatment Response mentioning

confidence: 99%

Phenotypic characterization of haemophilia B – Understanding the underlying biology of coagulation factor IX

Tjärnlund-Wolf

Lassila

2019

Haemophilia

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Haemophilia B is a recessive, X‐linked bleeding disorder due to inherited deficiency in vitamin K‐dependent coagulation factor IX (FIX). FIX activity levels, as a basis for the definition of disease severity, do not clearly correlate with bleeding phenotype, likely due to the multiple steps regulating coagulation. Timely, with the availability of extended half‐life products and successful steps in gene therapy, haemophilia B therapy is in an active developmental phase. Therefore, increased knowledge of the factors contributing to the variation of haemostatic and clinical outcome and response to therapy is welcomed. FIX acts at the crossroads of both the extrinsic and intrinsic pathways, and on the platelet procoagulant membrane at the site of vascular injury, and therefore, FIX biology is targeted for multiple effectors and regulators. The synthesis, cellular and molecular interactions, and elimination routes of FIX are not as well studied as for FVIII. The specific roles of magnesium in both platelet adhesion and FIX activation, and of vascular collagen at the haemostatic site of platelet adhesion and FIX residence are of particular interest. Biochemical and translational research on these issues should improve our understanding of the mechanisms involved, leading to the development of relevant assays that measure both haemostasis and treatment response. The latter is becoming increasingly important in the new era of haemophilia management and ultimately may lead to improved treatment strategies individually tailored to a patient's needs and cost‐efficiency.

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

Abstract: 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.

Cited by 36 publications

References 18 publications

Evaluation of chromogenic factor IX assays by automated protocols

Evaluation of chromogenic factor IX assays by automated protocols

Hemophilia management: Huge impact of a tiny difference

Phenotypic characterization of haemophilia B – Understanding the underlying biology of coagulation factor IX

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