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Updated: Jun 28, 2025
Author Spotlight: High-Sensitivity Tissue Factor Activity Assay for Plasma Diagnosis
Published on: December 29, 2023
Plasma tissue factor pathway inhibitor levels in coronavirus disease 2019 patients: a systematic review and
Saeed Hassani1, Mohammad Sayyadi1, Amir Almasi-Hashiani2,3
1Department of Medical Laboratory Sciences, School of Paramedical Sciences.
Insights
Tissue Factor Pathway Inhibitor (TFPI) levels are significantly elevated in moderate COVID-19 cases. This suggests TFPI may help regulate inflammation and hypercoagulation associated with severe COVID-19 disease.
Area of Science:
- Biochemistry
- Immunology
- Pathophysiology
Background:
- Inconsistent findings exist regarding the association between tissue factor pathway inhibitor (TFPI) and coronavirus disease 2019 (COVID-19) severity.
- Understanding this relationship is crucial for managing COVID-19 complications.
Purpose of the Study:
- To conduct a meta-analysis clarifying the relationship between TFPI levels and COVID-19 severity.
- To synthesize existing evidence on TFPI's role in COVID-19 pathophysiology.
Main Methods:
- A systematic literature search was performed across PubMed, Web of Science, and Scopus.
- Standardized mean difference (SMD) with 95% confidence intervals (CI) were used to summarize effect sizes.
- Study quality and risk of bias were assessed using the Newcastle-Ottawa scale.
Main Results:
- A significant increase in TFPI levels was observed in COVID-19 patients with moderate severity compared to healthy controls (SMD = 0.95 ng/ml, 95% CI [0.27, 1.63 ng/ml]).
- No significant TFPI level increase was found in mild or moderate COVID-19 cases when analyzed together.
- Increased TFPI concentrations correlated with elevated markers of inflammation, endothelial damage, and hypercoagulation.
Conclusions:
- Elevated TFPI levels in moderate COVID-19 suggest a potential role in mitigating hyper-inflammation and hypercoagulation.
- TFPI's anticoagulant and anti-inflammatory properties may be key in its response to COVID-19-induced pathological states.
Abstract:
Studies have suggested a relationship between tissue factor pathway inhibitor (TFPI) and coronavirus disease 2019 (COVID-19) severity. However, there is inconsistency in the findings of the studies. To enhance comprehension of this relationship, a meta-analysis was conducted. PubMed, Web of Science, and Scopus databases were searched to identify eligible studies. The mean difference was employed as effect measures and the standardized mean difference (SMD) and the 95% confidence interval (CI) were utilized as a summary statistic. Heterogeneity was assessed through the application of the chi-square test and the I2 statistic. The included studies' quality and risk of bias were assessed using the Newcastle-Ottawa assessment scale, adapted for case-control studies. A total of six studies were included with 684 cases and healthy controls (180 healthy controls and 504 COVID-19 patients with different severity, 76 mild, 292 moderate, and 136 severe). The analysis revealed a significant increase in the TFPI level in COVID-19 patients with moderate severity compared with healthy controls (SMD = 0.95 ng/ml, 95% confidence interval (CI) 0.27, 1.63 ng/ml; I2 : 87.2%). The increased TFPI level in mild and moderate COVID-19 was not significant, SMD = 0.68 ng/ml, 95% CI -0.64 to 2.0 ng/ml; I2 92.9% and SMD = 0.62 ng/ml, 95% CI -0.62 to 1.86 ng/ml; I2 91.5%, respectively. In addition, most studies indicate an association of the increased TFPI concentrations with increased markers of inflammation, endothelial damage, and hypercoagulation. Considering the anticoagulant and anti-inflammatory roles of TFPI, its increase seems to be aimed at modulating COVID-19-induced hyper-inflammation and hyper-coagulation state.
Systematic Review Registration:
PROSPERO CRD42023437353.
