Sensitive Measurement of Clinically Relevant Factor VIII Levels in Thrombin Generation Assays Requires Presence of Factor XIa.
Journal
Thrombosis and haemostasis
ISSN: 2567-689X
Titre abrégé: Thromb Haemost
Pays: Germany
ID NLM: 7608063
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
medline:
2
11
2023
pubmed:
27
5
2023
entrez:
26
5
2023
Statut:
ppublish
Résumé
Hemophilia A (HA) is characterized by decreased or absent factor VIII (FVIII) activity. Current FVIII assays are based on clotting time and thus only provide information about the initiation of coagulation. In contrast, thrombin generation assays (TGAs) can be used to measure the full coagulation spectrum of initiation, propagation, and termination that provide information on the whole course of thrombin generation and inhibition. However, the commercially available TG kits lack sensitivity for measurements of hemophilia plasma within lower FVIII ranges, which is essential for explaining differences in bleeding phenotypes in hemophiliacs at clinically low levels of FVIII. Optimization of the TGA for measurements of low FVIII levels in severe HA patients. TGA measurements were performed in severe HA pooled plasma ( TGA initiated by tissue factor (TF) alone at varying concentrations was unable to significantly differentiate between FVIII levels below 20%. In contrast, TGA activation with low concentrations of TF in presence of FXIa appeared to be highly sensitive for FVIII changes both in high and low ranges. In addition, a representative TGA curve at trough levels could only be produced using the dual TF/FXIa TGA. We propose a critical optimization for the setup of the TGA for measurements in severe HA plasma. The dual TF/FXIa TGA shows increased sensitivity, especially in lower FVIII ranges, which allows for better individual characterization at baseline, prediction of interventions, and follow-up.
Sections du résumé
BACKGROUND
BACKGROUND
Hemophilia A (HA) is characterized by decreased or absent factor VIII (FVIII) activity. Current FVIII assays are based on clotting time and thus only provide information about the initiation of coagulation. In contrast, thrombin generation assays (TGAs) can be used to measure the full coagulation spectrum of initiation, propagation, and termination that provide information on the whole course of thrombin generation and inhibition. However, the commercially available TG kits lack sensitivity for measurements of hemophilia plasma within lower FVIII ranges, which is essential for explaining differences in bleeding phenotypes in hemophiliacs at clinically low levels of FVIII.
AIMS
OBJECTIVE
Optimization of the TGA for measurements of low FVIII levels in severe HA patients.
METHODS
METHODS
TGA measurements were performed in severe HA pooled plasma (
RESULTS
RESULTS
TGA initiated by tissue factor (TF) alone at varying concentrations was unable to significantly differentiate between FVIII levels below 20%. In contrast, TGA activation with low concentrations of TF in presence of FXIa appeared to be highly sensitive for FVIII changes both in high and low ranges. In addition, a representative TGA curve at trough levels could only be produced using the dual TF/FXIa TGA.
CONCLUSION
CONCLUSIONS
We propose a critical optimization for the setup of the TGA for measurements in severe HA plasma. The dual TF/FXIa TGA shows increased sensitivity, especially in lower FVIII ranges, which allows for better individual characterization at baseline, prediction of interventions, and follow-up.
Identifiants
pubmed: 37236229
doi: 10.1055/a-2101-7961
pmc: PMC10615588
doi:
Substances chimiques
Factor VIII
9001-27-8
Thrombin
EC 3.4.21.5
Factor XIa
EC 3.4.21.27
Thromboplastin
9035-58-9
Hemostatics
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1034-1041Informations de copyright
The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).
Déclaration de conflit d'intérêts
T.M.H. is inventor on WO2013028069A1 Thermostable inhibitors of activation of the blood clotting system through contact with foreign surfaces.
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