Validation of factor VIII activity for monitoring standard and extended half-life products and correlation to thrombin generation assays
(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 6–32%, 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.
(Less)
- author
- Augustsson, Cecilia ; Norström, Eva LU ; Lind, Vivian ; Martin, Myriam LU ; Astermark, Jan LU and Strandberg, Karin LU
- organization
- publishing date
- 2021-05-01
- 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
-
- scopus:85104306007
- pmid:33866649
- 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
- 2023-11-23 01:53:02
@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 6–32%, 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}},
}