title: Recombinant to modified factor VIII and factor IX - chromogenic and one-stage assays issues.
abstract: The recent development of modified recombinant factor VIII (FVIII) and factor IX (FIX) therapeutic products with extended half-lives will create challenges for the haemostasis laboratory in obtaining recovery estimates of these products in clinical samples using existing assays. The new long-acting therapeutic concentrates contain molecular modifications of Fc fusion, site-specific of polyethylene glycol or albumin fusion. The optimum methods for monitoring each new product will need to be assessed individually and laboratories should select an assay which gives similar results to the assay used to assign potency to the product in question. For some extended half-life FVIII and FIX products some one stage assays are entirely unsuitable for monitoring purposes. For most products and assay reagents studied so far, and reviewed in this manuscript, chromogenic FVIII or FIX assays can be safely used with conventional plasma standards. If one stage assays are used then they should be performed using carefully selected reagents/methods which have been shown to recover activity close to the labelled potency for the specific product being monitored.
authors.affiliation: Sheffield Haemophilia and Thrombosis Centre, Sheffield, UK.
authors.forename: S
authors.initials: S
authors.lastname: Kitchen
authors.affiliation: Institute of Haematology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Kershaw
authors.affiliation: Laboratory Corporation of America, Colorado Coagulation, Denver, CO, USA.
authors.forename: S
authors.initials: S
authors.lastname: Tiefenbacher
mesh_terms: D001780:Blood Coagulation Tests; D002863:Chromogenic Compounds / Q000737:chemistry*; D005164:Factor IX / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D005169:Factor VIII / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D011994:Recombinant Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics
chemical_list: D002863:Chromogenic Compounds; D011994:Recombinant Proteins; D005169:Factor VIII; D005164:Factor IX
keywords: FVIII assays; chromogenic assay; extended half-life products; factor IX assay; one-stage assay