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Updated: Jun 6, 2025
Author Spotlight: High-Sensitivity Tissue Factor Activity Assay for Plasma Diagnosis
Published on: December 29, 2023
Extracellular vesicle tissue factor and tissue factor pathway inhibitor are independent discriminators of
Anna K Tobiasch1, Georg F Lehner1, Clemens Feistritzer2
1Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Innsbruck, Austria.
Insights
Tissue factor pathway inhibitor (TFPI) and extracellular vesicle-associated tissue factor procoagulant activity (TF-PCA) can help identify sepsis-induced disseminated intravascular coagulopathy (DIC). These markers may improve early diagnosis and treatment strategies for sepsis patients.
Area of Science:
- Hematology
- Critical Care Medicine
- Pathophysiology
Background:
- Sepsis-induced disseminated intravascular coagulopathy (DIC) is a severe condition with high mortality.
- Endothelial activation and extracellular vesicles (EVs) are implicated in the development of DIC.
Purpose of the Study:
- To evaluate the diagnostic accuracy of E-selectin, EVs, tissue factor (TF), and TF pathway inhibitor (TFPI) in sepsis-induced coagulopathy.
- To assess the predictive value of these markers for the progression to overt DIC.
Main Methods:
- Prospective, single-center study involving 87 sepsis patients.
- Plasma samples collected within 24 hours of sepsis diagnosis and followed for 5 days.
- Overt DIC diagnosed using the International Society on Thrombosis and Haemostasis (ISTH) DIC score.
Main Results:
- TFPI levels and EV-associated TF procoagulant activity (TF-PCA) differentiated between sepsis patients with and without DIC (AUC = 0.76, P = .0002).
- High TF-PCA levels (>1.38 pg/mL) demonstrated high specificity (95%) for sepsis-associated DIC.
- Elevated TFPI levels at admission significantly increased the hazard ratio for progressing to DIC.
Conclusions:
- TF-PCA and TFPI play crucial roles in the early stages of sepsis-induced DIC.
- Functionally active, EV-associated TF, rather than TF antigen levels, shows predictive potential for DIC.
- These findings may lead to improved diagnostic and therapeutic strategies for sepsis-induced DIC.
Background:
Sepsis-induced disseminated intravascular coagulopathy (DIC) remains a challenging clinical entity associated with significant morbidity and mortality. Endothelial injury or activation and extracellular vesicles (EV) are postulated as important determinants of DIC.
Objectives:
The aim of this study was to test the discriminatory ability of E-selectin, EV, tissue factor (TF) and TF pathway inhibitor (TFPI) in sepsis-induced coagulopathy.
Methods:
In this prospective, single-center study, we collected plasma samples within 24 hours after sepsis diagnosis and followed these patients for 5 consecutive days. Overt DIC was determined by the International Society on Thrombosis and Haemostasis (ISTH) DIC score. Eighty-seven sepsis patients were recruited (35 with overt DIC) who presented with increased levels of EV, EV-associated TF procoagulant activity (TF-PCA), E-selectin, TF, and TFPI at admission compared with healthy subjects.
Results:
Only TFPI levels and TF-PCA discriminated between sepsis patients with or without DIC (area under the curve = 0.76; P = .0002). Increased TF-PCA was not sensitive in detecting sepsis-associated DIC; however, levels above 1.38 pg/mL showed high specificity in this cohort (sensitivity 27%, specificity 95%). The hazard ratio to progress to DIC over 5 days was 1.14 (95% CI, 0.64-2.07) for TF-PCA levels of 0.5 pg/mL or higher and 3.18 (95% CI, 1.74-5.79) for TFPI levels of 22.28 ng/mL or higher at admission.
Conclusion:
These findings highlight the pivotal roles of TF-PCA and TFPI in an early phase of sepsis-induced DIC. Only EV-associated and functionally active TF and not TF antigen levels showed a predictive potential regarding DIC. These novel results might support the improvement of diagnostic or even therapeutic strategies to mitigate the devastating consequences of DIC in septic patients.
