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. 2023 Aug 10;12(16):5223.
doi: 10.3390/jcm12165223.

Changes in the Fibrinolytic System of Patients Infected with Severe Acute Respiratory Syndrome Coronavirus 2

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Changes in the Fibrinolytic System of Patients Infected with Severe Acute Respiratory Syndrome Coronavirus 2

Esra'a Abudouleh et al. J Clin Med. .

Abstract

Introduction: In this study, coagulation and fibrinolysis parameters and their association with disease severity were investigated in coronavirus disease (COVID-19) patients.

Materials and methods: COVID-19 patients (n = 446) admitted to our institute between 21 February 2021 and 17 March 2022, were recruited. Clinical data and staging were collected from all patients. Blood samples were collected and analyzed for several parameters of fibrinolysis and coagulation, including alpha-2-antiplasmin(α2AP) and plasminogen, thrombin activatable fibrinolysis inhibitor (TAFI), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), D-dimer, and fibrinogen levels.

Results: The TAFI, fibrinogen, and tPA levels were significantly higher in participants who died compared to that of patients who recovered (p < 0.001). However, PAI-1, tPA, and TAFI were significantly higher in patients admitted to the ICU than those of the healthy controls (p < 0.001 for PAI-1 and tPA; p = 0.0331 for TAFI). Our results showed that stage C and D COVID-19 patients had significantly higher levels of PAI-1 (p = 0.003). Furthermore, stage D COVID-19 patients had significantly higher tPA and TAFI values (p = 0.003).

Conclusions: Hypofibrinolysis was the most prevalent condition among patients with severe COVID-19. In this study, several coagulation markers were elevated, making them suitable prognostic markers for hypofibrinolysis.

Keywords: coagulation; coronavirus disease; plasminogen activator inhibitor; thrombin activatable fibrinolysis inhibitor; tissue plasminogen activator.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Plasma levels of different coagulation factors in COVID-19 patients. Plasma was isolated from patients who had died due to COVID-19 and those recovering from the disease (AE). Patients with thrombosis and those without thrombosis were isolated for α2AP, plasminogen, PAI-1, tPA, and TAFI (FJ) tests. Groups were compared by using Mann–Whitney test, while normally distributed data were studied using a two-sided t-test. Levels of the coagulation factors and p values are shown in each panel. The dotted lines represent the upper limit of the normal range for the plasma level of all the coagulation markers. Data are represented as medians with 95% CI of n = 36 (dead patients), n = 197 (recovery patients), n = 22 (thrombosis patients), and n = 211 (no thrombosis).
Figure 2
Figure 2
Coagulation parameters in ICU and non-ICU COVID-19 patients. Plasma isolated from blood samples of healthy individuals and COVID-19 patients either admitted or not admitted to the ICU were assessed for α2AP (A), plasminogen (B), PAI-1(C), tPA (D), and TAFI (E) were compared using the Kruskal–Wallis test. Levels of the aforementioned coagulation factors and p values are shown in each panel. The dotted lines represent the upper limit of the normal range for the plasma levels of all the coagulation markers. Data are represented as medians with 95% CI of n = 130 (ICU), n = 103 (non-ICU), n = 40 (healthy control).
Figure 3
Figure 3
Impact of COVID-19 disease stage and plasma levels of coagulation factors in patients. Patients were grouped into four stages (AD), and the plasma levels of PAI-1, tPA, and TAFI were compared for all the stages (AE). Data are presented as medians with 95% CI, and data points represent individuals recruited for each group.

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