Plasma tissue factor pathway inhibitor levels in coronavirus disease 2019 patients: a systematic review and meta-analysis

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 I 2 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; I 2: 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; I 2 92.9% and SMD = 0.62 ng/ml, 95% CI −0.62 to 1.86 ng/ml; I 2 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