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Laboratory issues in gene therapy and emicizumab.
Haemophilia. 2021 Feb; 27 Suppl 3:142-147.H

Abstract

The treatment options for the haemostatic disorders, haemophilia A and haemophilia B, have progressed rapidly over the last decade. The introduction of extended half-life recombinant factor VIII (FVIII) and factor IX (FIX) concentrates to replace these missing clotting factors highlighted discordance between one-stage activated partial thromboplastin time (APTT)-based clotting factor assays and chromogenic factor assays with some products. This raised awareness of the importance of investigation of potential reagent or assay differences by pharmaceutical companies. In 2017, the FVIII mimetic, emicizumab, was approved as a prophylactic treatment for haemophilia A patients with anti-FVIII inhibitors. The mechanism of action of emicizumab causes interference with some commonly used haemostasis tests including the APTT and its associated one-stage APTT-based clotting assays. Chromogenic assays may also be affected but this is dependent on the particular constituents of the reagents. Chromogenic assays containing human factor IXa (FIXa) and factor X (FX) are sensitive to the presence of emicizumab but those containing bovine FIXa and FX are unaffected. Many haemostasis laboratories have been required to evaluate new assays to enable accurate monitoring of emicizumab in patient plasma. A number of gene therapy approaches have been trialled in both haemophilia A and haemophilia B but there are scant data published on the measurement of FVIII and FIX in these patients and whether there are discrepancies between reagents or assay methodologies.

Authors+Show Affiliations

Department of Coagulation, Sheffield Haemophilia and Thrombosis Centre, Sheffield, UK.UK National External Quality Assurance Scheme (NEQAS) for Blood Coagulation, Sheffield, UK.Colorado Coagulation, Laboratory Corporation of America® Holdings, Englewood, CO, USA.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32469128

Citation

Bowyer, Annette E., et al. "Laboratory Issues in Gene Therapy and Emicizumab." Haemophilia : the Official Journal of the World Federation of Hemophilia, vol. 27 Suppl 3, 2021, pp. 142-147.
Bowyer AE, Lowe AE, Tiefenbacher S. Laboratory issues in gene therapy and emicizumab. Haemophilia. 2021;27 Suppl 3:142-147.
Bowyer, A. E., Lowe, A. E., & Tiefenbacher, S. (2021). Laboratory issues in gene therapy and emicizumab. Haemophilia : the Official Journal of the World Federation of Hemophilia, 27 Suppl 3, 142-147. https://doi.org/10.1111/hae.13976
Bowyer AE, Lowe AE, Tiefenbacher S. Laboratory Issues in Gene Therapy and Emicizumab. Haemophilia. 2021;27 Suppl 3:142-147. PubMed PMID: 32469128.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Laboratory issues in gene therapy and emicizumab. AU - Bowyer,Annette E, AU - Lowe,Anna E, AU - Tiefenbacher,Stefan, Y1 - 2020/05/29/ PY - 2020/01/21/received PY - 2020/02/24/revised PY - 2020/03/04/accepted PY - 2020/5/30/pubmed PY - 2021/9/25/medline PY - 2020/5/30/entrez KW - chromogenic assay KW - emicizumab KW - factor IX KW - factor VIII KW - gene therapy KW - haemophilia SP - 142 EP - 147 JF - Haemophilia : the official journal of the World Federation of Hemophilia JO - Haemophilia VL - 27 Suppl 3 N2 - The treatment options for the haemostatic disorders, haemophilia A and haemophilia B, have progressed rapidly over the last decade. The introduction of extended half-life recombinant factor VIII (FVIII) and factor IX (FIX) concentrates to replace these missing clotting factors highlighted discordance between one-stage activated partial thromboplastin time (APTT)-based clotting factor assays and chromogenic factor assays with some products. This raised awareness of the importance of investigation of potential reagent or assay differences by pharmaceutical companies. In 2017, the FVIII mimetic, emicizumab, was approved as a prophylactic treatment for haemophilia A patients with anti-FVIII inhibitors. The mechanism of action of emicizumab causes interference with some commonly used haemostasis tests including the APTT and its associated one-stage APTT-based clotting assays. Chromogenic assays may also be affected but this is dependent on the particular constituents of the reagents. Chromogenic assays containing human factor IXa (FIXa) and factor X (FX) are sensitive to the presence of emicizumab but those containing bovine FIXa and FX are unaffected. Many haemostasis laboratories have been required to evaluate new assays to enable accurate monitoring of emicizumab in patient plasma. A number of gene therapy approaches have been trialled in both haemophilia A and haemophilia B but there are scant data published on the measurement of FVIII and FIX in these patients and whether there are discrepancies between reagents or assay methodologies. SN - 1365-2516 UR - https://www.unboundmedicine.com/medline/citation/32469128/Laboratory_issues_in_gene_therapy_and_emicizumab_ L2 - https://doi.org/10.1111/hae.13976 DB - PRIME DP - Unbound Medicine ER -