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Validation of factor VIII activity for monitoring standard and extended half-life products and correlation to thrombin generation assays

Augustsson, Cecilia ; Norström, Eva LU ; Lind, Vivian ; Martin, Myriam LU ; Astermark, Jan LU and Strandberg, Karin LU (2021) In Haemophilia 27(3). p.494-500
Abstract

Introduction: Monitoring replacement therapy with standard and extended half-life (EHL) products is challenging, since one-stage assay (OSA) and chromogenic substrate assay (CSA) results may differ significantly. Recent recommendations include local validation of each new product with recovery within 20–30%, depending on activity level. Aim: To validate factor VIII (FVIII) activity for monitoring products in clinical use on Atellica Coag and to correlate it with thrombin generation. Methods: Plasma samples spiked with Advate®, Elocta®, Adynovi®, Nuwiq®, NovoEight® and Afstyla® (0.05, 0.20, 0.50 and 0.80 IU/ml) were analysed using Atellica Coag 360 with CSA-1 (Coatest SP)... (More)

Introduction: Monitoring replacement therapy with standard and extended half-life (EHL) products is challenging, since one-stage assay (OSA) and chromogenic substrate assay (CSA) results may differ significantly. Recent recommendations include local validation of each new product with recovery within 20–30%, depending on activity level. Aim: To validate factor VIII (FVIII) activity for monitoring products in clinical use on Atellica Coag and to correlate it with thrombin generation. Methods: Plasma samples spiked with Advate®, Elocta®, Adynovi®, Nuwiq®, NovoEight® and Afstyla® (0.05, 0.20, 0.50 and 0.80 IU/ml) were analysed using Atellica Coag 360 with CSA-1 (Coatest SP) and CSA-2 (FVIII chromogenic), and OSA (Actin FS). Thrombin generation was performed using two thrombin generation assays (TGA-1 (Thrombinoscope) and TGA-2 (Technothrombin). Results: All products at levels above 0.05 IU/ml, except Adynovi, showed acceptable recovery using CSA-1, whereas measurements using CSA-2 gave more results outside the target level. All products, except Afstyla, showed acceptable recovery using OSA. Correlation between CSA-1 and OSA was excellent (r2=1.0) with biases of 6–3​2%, depending on FVIII product. A clear dose-response was seen for all thrombin generation parameters and products using both methods, except at low levels for lag time using TGA-1. With CSA-1 as an independent variable, the correlations to thrombin peak (measured with TGA-2) were good (r2 =.8–.9). Conclusion: Our data revealed good correlation and acceptable bias between CSA and OSA using our sets of reagents, methods and analyser in spiked samples. Thrombin generation gave good correlation to CSA-1 factor activity and is a possible complement to factor activity assays.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
blood coagulation tests, coagulants, drug monitoring, factor VIII, haemophilia A
in
Haemophilia
volume
27
issue
3
pages
7 pages
publisher
Wiley-Blackwell
external identifiers
  • pmid:33866649
  • scopus:85104306007
ISSN
1351-8216
DOI
10.1111/hae.14317
language
English
LU publication?
yes
id
9266c9b7-ea89-478f-86ab-018b313adccc
date added to LUP
2021-04-26 14:47:12
date last changed
2022-09-24 21:41:03
@article{9266c9b7-ea89-478f-86ab-018b313adccc,
  abstract     = {{<p>Introduction: Monitoring replacement therapy with standard and extended half-life (EHL) products is challenging, since one-stage assay (OSA) and chromogenic substrate assay (CSA) results may differ significantly. Recent recommendations include local validation of each new product with recovery within 20–30%, depending on activity level. Aim: To validate factor VIII (FVIII) activity for monitoring products in clinical use on Atellica Coag and to correlate it with thrombin generation. Methods: Plasma samples spiked with Advate<sup>®</sup>, Elocta<sup>®</sup>, Adynovi<sup>®</sup>, Nuwiq<sup>®</sup>, NovoEight<sup>®</sup> and Afstyla<sup>®</sup> (0.05, 0.20, 0.50 and 0.80 IU/ml) were analysed using Atellica Coag 360 with CSA-1 (Coatest SP) and CSA-2 (FVIII chromogenic), and OSA (Actin FS). Thrombin generation was performed using two thrombin generation assays (TGA-1 (Thrombinoscope) and TGA-2 (Technothrombin). Results: All products at levels above 0.05 IU/ml, except Adynovi, showed acceptable recovery using CSA-1, whereas measurements using CSA-2 gave more results outside the target level. All products, except Afstyla, showed acceptable recovery using OSA. Correlation between CSA-1 and OSA was excellent (r<sup>2</sup>=1.0) with biases of 6–3​2%, depending on FVIII product. A clear dose-response was seen for all thrombin generation parameters and products using both methods, except at low levels for lag time using TGA-1. With CSA-1 as an independent variable, the correlations to thrombin peak (measured with TGA-2) were good (r<sup>2</sup> =.8–.9). Conclusion: Our data revealed good correlation and acceptable bias between CSA and OSA using our sets of reagents, methods and analyser in spiked samples. Thrombin generation gave good correlation to CSA-1 factor activity and is a possible complement to factor activity assays.</p>}},
  author       = {{Augustsson, Cecilia and Norström, Eva and Lind, Vivian and Martin, Myriam and Astermark, Jan and Strandberg, Karin}},
  issn         = {{1351-8216}},
  keywords     = {{blood coagulation tests; coagulants; drug monitoring; factor VIII; haemophilia A}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{3}},
  pages        = {{494--500}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Haemophilia}},
  title        = {{Validation of factor VIII activity for monitoring standard and extended half-life products and correlation to thrombin generation assays}},
  url          = {{http://dx.doi.org/10.1111/hae.14317}},
  doi          = {{10.1111/hae.14317}},
  volume       = {{27}},
  year         = {{2021}},
}