Cargando…

The influence of corn trypsin inhibitor on the contribution of coagulation determinants to the Technoclone Thrombin Generation Assay (TGA) and the Calibrated Automated Thrombogram (CAT)

In thrombin generation (TG) assays, regarded as global coagulation tests, contact activation is considered a major problem which can be eliminated by adding Corn Trypsin Inhibitor (CTI). In previous studies, however, venous thrombosis risk prediction using TG assays did not improve after CTI additio...

Descripción completa

Detalles Bibliográficos
Autores principales: Touw, Carolina E., de Jong, Ype, van Hylckama Vlieg, Astrid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880747/
https://www.ncbi.nlm.nih.gov/pubmed/35213588
http://dx.doi.org/10.1371/journal.pone.0263960
_version_ 1784659297127366656
author Touw, Carolina E.
de Jong, Ype
van Hylckama Vlieg, Astrid
author_facet Touw, Carolina E.
de Jong, Ype
van Hylckama Vlieg, Astrid
author_sort Touw, Carolina E.
collection PubMed
description In thrombin generation (TG) assays, regarded as global coagulation tests, contact activation is considered a major problem which can be eliminated by adding Corn Trypsin Inhibitor (CTI). In previous studies, however, venous thrombosis risk prediction using TG assays did not improve after CTI addition. However, it is unknown whether CTI addition could help to detect subtle but relevant nuances in determinants of TG, making the assay more suitable to detect disturbances in the coagulation system. This study’s objective was to assess whether the addition of CTI is associated with a broader contribution of individual coagulation factors to the total amount of thrombin formed in Calibrated Automated Thrombogram (CAT) and Technoclone Thrombin Generation Assay (TGA). Thrombin generation was measured in 326 healthy individuals from THE VTE study at very low tissue factor concentrations, with and without addition of CTI prior to blood sampling. The influence of several coagulation factors on total amount of thrombin formed, i.e. area under the curve (AUC) or endogenous thrombin potential (ETP), was analysed using multiple linear regression with standardisation of all values resulting in Z-scores with 95% confidence intervals (95%CI). Association between coagulation factors and TG changed minimally after addition of CTI. Largest changes after CTI addition were found for following factors: for CAT: free protein S (from 0.00 (95%CI -0.12 to 0.12) to -0.29 (95%CI -0.43 to -0.15)) and protein S (from -0.05 (95%CI -0.18 to 0.08) to -0.21 (95%CI -0.37 to -0.05)); for TGA: antithrombin (from -0.11 (-0.23 to 0.02) to -0.19 (-0.30 to -0.07)), factor VIII (from 0.15 (0.03 to 0.27) to 0.24 (0.13 to 0.36)) and fibrinogen (from 0.12 (-0.01 to 0.26) to 0.19 (0.06 to 0.32)). In conclusion, there is no clear trend towards a broader contribution of coagulation factors in samples handled with CTI compared with those handled without CTI.
format Online
Article
Text
id pubmed-8880747
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-88807472022-02-26 The influence of corn trypsin inhibitor on the contribution of coagulation determinants to the Technoclone Thrombin Generation Assay (TGA) and the Calibrated Automated Thrombogram (CAT) Touw, Carolina E. de Jong, Ype van Hylckama Vlieg, Astrid PLoS One Research Article In thrombin generation (TG) assays, regarded as global coagulation tests, contact activation is considered a major problem which can be eliminated by adding Corn Trypsin Inhibitor (CTI). In previous studies, however, venous thrombosis risk prediction using TG assays did not improve after CTI addition. However, it is unknown whether CTI addition could help to detect subtle but relevant nuances in determinants of TG, making the assay more suitable to detect disturbances in the coagulation system. This study’s objective was to assess whether the addition of CTI is associated with a broader contribution of individual coagulation factors to the total amount of thrombin formed in Calibrated Automated Thrombogram (CAT) and Technoclone Thrombin Generation Assay (TGA). Thrombin generation was measured in 326 healthy individuals from THE VTE study at very low tissue factor concentrations, with and without addition of CTI prior to blood sampling. The influence of several coagulation factors on total amount of thrombin formed, i.e. area under the curve (AUC) or endogenous thrombin potential (ETP), was analysed using multiple linear regression with standardisation of all values resulting in Z-scores with 95% confidence intervals (95%CI). Association between coagulation factors and TG changed minimally after addition of CTI. Largest changes after CTI addition were found for following factors: for CAT: free protein S (from 0.00 (95%CI -0.12 to 0.12) to -0.29 (95%CI -0.43 to -0.15)) and protein S (from -0.05 (95%CI -0.18 to 0.08) to -0.21 (95%CI -0.37 to -0.05)); for TGA: antithrombin (from -0.11 (-0.23 to 0.02) to -0.19 (-0.30 to -0.07)), factor VIII (from 0.15 (0.03 to 0.27) to 0.24 (0.13 to 0.36)) and fibrinogen (from 0.12 (-0.01 to 0.26) to 0.19 (0.06 to 0.32)). In conclusion, there is no clear trend towards a broader contribution of coagulation factors in samples handled with CTI compared with those handled without CTI. Public Library of Science 2022-02-25 /pmc/articles/PMC8880747/ /pubmed/35213588 http://dx.doi.org/10.1371/journal.pone.0263960 Text en © 2022 Touw et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Touw, Carolina E.
de Jong, Ype
van Hylckama Vlieg, Astrid
The influence of corn trypsin inhibitor on the contribution of coagulation determinants to the Technoclone Thrombin Generation Assay (TGA) and the Calibrated Automated Thrombogram (CAT)
title The influence of corn trypsin inhibitor on the contribution of coagulation determinants to the Technoclone Thrombin Generation Assay (TGA) and the Calibrated Automated Thrombogram (CAT)
title_full The influence of corn trypsin inhibitor on the contribution of coagulation determinants to the Technoclone Thrombin Generation Assay (TGA) and the Calibrated Automated Thrombogram (CAT)
title_fullStr The influence of corn trypsin inhibitor on the contribution of coagulation determinants to the Technoclone Thrombin Generation Assay (TGA) and the Calibrated Automated Thrombogram (CAT)
title_full_unstemmed The influence of corn trypsin inhibitor on the contribution of coagulation determinants to the Technoclone Thrombin Generation Assay (TGA) and the Calibrated Automated Thrombogram (CAT)
title_short The influence of corn trypsin inhibitor on the contribution of coagulation determinants to the Technoclone Thrombin Generation Assay (TGA) and the Calibrated Automated Thrombogram (CAT)
title_sort influence of corn trypsin inhibitor on the contribution of coagulation determinants to the technoclone thrombin generation assay (tga) and the calibrated automated thrombogram (cat)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880747/
https://www.ncbi.nlm.nih.gov/pubmed/35213588
http://dx.doi.org/10.1371/journal.pone.0263960
work_keys_str_mv AT touwcarolinae theinfluenceofcorntrypsininhibitoronthecontributionofcoagulationdeterminantstothetechnoclonethrombingenerationassaytgaandthecalibratedautomatedthrombogramcat
AT dejongype theinfluenceofcorntrypsininhibitoronthecontributionofcoagulationdeterminantstothetechnoclonethrombingenerationassaytgaandthecalibratedautomatedthrombogramcat
AT vanhylckamavliegastrid theinfluenceofcorntrypsininhibitoronthecontributionofcoagulationdeterminantstothetechnoclonethrombingenerationassaytgaandthecalibratedautomatedthrombogramcat
AT touwcarolinae influenceofcorntrypsininhibitoronthecontributionofcoagulationdeterminantstothetechnoclonethrombingenerationassaytgaandthecalibratedautomatedthrombogramcat
AT dejongype influenceofcorntrypsininhibitoronthecontributionofcoagulationdeterminantstothetechnoclonethrombingenerationassaytgaandthecalibratedautomatedthrombogramcat
AT vanhylckamavliegastrid influenceofcorntrypsininhibitoronthecontributionofcoagulationdeterminantstothetechnoclonethrombingenerationassaytgaandthecalibratedautomatedthrombogramcat