New functional test for the TFPIα cofactor activity of Protein S working in synergy with FV-Short
Dahlbäck, Björn LU ; Guo, Li Jun LU ; Zöller, Bengt LU
and Tran, Sinh
LU
(2019)
In Journal of Thrombosis and Haemostasis
17(4).
p.585-595
- Abstract
Essentials Protein S and FV-Short are synergistic cofactors to Tissue Factor Pathway Inhibitor α (TFPIα). An assay for the TFPIα synergistic cofactor activity of protein S with FV-Short was developed. The assay was specific for the synergistic TFPIα-cofactor activity of free protein S. Protein S deficient individuals with known mutations were correctly distinguished from controls. Summary: Background Protein S is an anticoagulant cofactor to both activated protein C and tissue factor pathway inhibitor (TFPIα). The TFPIα-cofactor activity of protein S is stimulated by a short isoform of factor V (FV-Short), the two proteins functioning in synergy. Objective Using the synergistic TFPIα-cofactor activity between protein S and FV-Short to... (More)
Essentials Protein S and FV-Short are synergistic cofactors to Tissue Factor Pathway Inhibitor α (TFPIα). An assay for the TFPIα synergistic cofactor activity of protein S with FV-Short was developed. The assay was specific for the synergistic TFPIα-cofactor activity of free protein S. Protein S deficient individuals with known mutations were correctly distinguished from controls. Summary: Background Protein S is an anticoagulant cofactor to both activated protein C and tissue factor pathway inhibitor (TFPIα). The TFPIα-cofactor activity of protein S is stimulated by a short isoform of factor V (FV-Short), the two proteins functioning in synergy. Objective Using the synergistic TFPIα-cofactor activity between protein S and FV-Short to develop a functional test for plasma protein S. Patients/Methods TFPIα-mediated inhibition of FXa in the presence of FV-Short, protein S and negatively charged phospholipid vesicles was monitored in time by synthetic substrate S2765. TFPIα, FXa and FV-Short were purified proteins, whereas diluted plasma from protein S deficient patients or controls were used as source for protein S. Results The assay was specific for free protein S demonstrating good correlation to free protein S plasma levels (r = 0.92) with a Y-axis intercept of −5%. Correlation to concentrations of total protein S (free and C4BPβ+-bound) was lower (r = 0.88) and the Y-axis intercept was +46%, which is consistent with the specificity for free protein S. The test distinguished protein S-deficient individuals from 6 families with known ProS1 mutations from family members having no mutation. Protein S levels of warfarin-treated protein S deficient cases were lower than protein S in cases treated with warfarin for other causes. Conclusions We describe a new assay measuring the TFPIα-cofactor activity of plasma protein S. The test identifies type I/III protein S deficiencies and will be a useful tool to detect type II protein S deficiency having defective TFPIα-cofactor activity.
(Less)
- author
- Dahlbäck, Björn
LU
; Guo, Li Jun
LU
; Zöller, Bengt
LU
and Tran, Sinh
LU
- organization
- publishing date
- 2019-02-11
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- deep venous thrombosis, factor V, factor X, protein S, TFPI
- in
- Journal of Thrombosis and Haemostasis
- volume
- 17
- issue
- 4
- pages
- 585 - 595
- publisher
- Wiley-Blackwell
- external identifiers
-
- scopus:85062797499
- pmid:30740865
- ISSN
- 1538-7933
- DOI
- 10.1111/jth.14405
- language
- English
- LU publication?
- yes
- id
- 3c83e146-7ab6-419f-aa3e-bdfe78d9b531
- date added to LUP
- 2019-03-20 14:48:06
- date last changed
- 2024-02-14 20:08:22
@article{3c83e146-7ab6-419f-aa3e-bdfe78d9b531,
abstract = {{<p>Essentials Protein S and FV-Short are synergistic cofactors to Tissue Factor Pathway Inhibitor α (TFPIα). An assay for the TFPIα synergistic cofactor activity of protein S with FV-Short was developed. The assay was specific for the synergistic TFPIα-cofactor activity of free protein S. Protein S deficient individuals with known mutations were correctly distinguished from controls. Summary: Background Protein S is an anticoagulant cofactor to both activated protein C and tissue factor pathway inhibitor (TFPIα). The TFPIα-cofactor activity of protein S is stimulated by a short isoform of factor V (FV-Short), the two proteins functioning in synergy. Objective Using the synergistic TFPIα-cofactor activity between protein S and FV-Short to develop a functional test for plasma protein S. Patients/Methods TFPIα-mediated inhibition of FXa in the presence of FV-Short, protein S and negatively charged phospholipid vesicles was monitored in time by synthetic substrate S2765. TFPIα, FXa and FV-Short were purified proteins, whereas diluted plasma from protein S deficient patients or controls were used as source for protein S. Results The assay was specific for free protein S demonstrating good correlation to free protein S plasma levels (r = 0.92) with a Y-axis intercept of −5%. Correlation to concentrations of total protein S (free and C4BPβ+-bound) was lower (r = 0.88) and the Y-axis intercept was +46%, which is consistent with the specificity for free protein S. The test distinguished protein S-deficient individuals from 6 families with known ProS1 mutations from family members having no mutation. Protein S levels of warfarin-treated protein S deficient cases were lower than protein S in cases treated with warfarin for other causes. Conclusions We describe a new assay measuring the TFPIα-cofactor activity of plasma protein S. The test identifies type I/III protein S deficiencies and will be a useful tool to detect type II protein S deficiency having defective TFPIα-cofactor activity.</p>}},
author = {{Dahlbäck, Björn and Guo, Li Jun and Zöller, Bengt and Tran, Sinh}},
issn = {{1538-7933}},
keywords = {{deep venous thrombosis; factor V; factor X; protein S; TFPI}},
language = {{eng}},
month = {{02}},
number = {{4}},
pages = {{585--595}},
publisher = {{Wiley-Blackwell}},
series = {{Journal of Thrombosis and Haemostasis}},
title = {{New functional test for the TFPIα cofactor activity of Protein S working in synergy with FV-Short}},
url = {{http://dx.doi.org/10.1111/jth.14405}},
doi = {{10.1111/jth.14405}},
volume = {{17}},
year = {{2019}},
}