Neutrophil extracellular traps are associated with enhanced procoagulant activity in liver cirrhosis patients with portal vein thrombosis

Abstract

Objective: Patients with liver cirrhosis (LC) commonly exhibit hypercoagulability and tend to develop thrombosis. Neutrophil extracellular traps (NETs) are associated with a variety of thrombotic conditions, but their possible value in portal vein thrombosis (PVT) is not known. We assessed whether NETs promote thrombosis and contribute to the procoagulant state in patients with LC.

Methods: The circulating levels of NETs markers (myeloperoxidase, neutrophil elastase, citrullinated histone H3) were measured in 72 patients (median age, 55 years; 48 [66.7%] men) with LC from September 2020 to February 2021. Then they were divided into two groups: patients with or without PVT. NETs procoagulant activity was assessed based on thrombin-antithrombin complex (TAT complex) and Factor X. The levels of plasma markers were determined by ELISA.

Results: There were 28 patients with PVT and 44 patients without PVT. The levels of NETs markers and hypercoagulability markers in the plasma of cirrhosis patients with PVT were significantly higher than those of cirrhosis patients without PVT (p < 0.05). Additionally, the levels of the NETs markers correlated with TAT complex and Factor X (Spearman correlation rho >0.73, p < 0.0001).

Conclusions: Neutrophil extracellular traps seem to enhance procoagulant activity in LC patients with PVT; thus, they may be a practical predictor of PVT as well as a rapid and easy-to-use diagnostic and treatment guide for PVT in patients with cirrhosis.

Keywords: hypercoagulability; liver cirrhosis; neutrophil extracellular traps; portal vein thrombosis.

FIGURE 1

Flowchart of this study

FIGURE 2

Patients with PVT had higher serum NETs markers levels compared with non‐PVT patients. Levels of MPO (A), NE (B), and CitH3 (C) in the PVT group (n = 28) were significantly higher than those in the non‐PVT group (n = 44). **p < 0.01; *p < 0.05

FIGURE 3

Relationships between MPO, NE, and CitH3. Levels of MPO were positively associated with circulating levels of NE and CitH3 in PVT patients (A and B). Levels of NE were positively associated with circulating levels of MPO and CitH3 in PVT patients (A and C). Levels of CitH3 were positively associated with circulating levels of MPO and NE in PVT patients (B and C)

FIGURE 4

Patients with PVT exhibit hypercoagulability compared with non‐PVT patients. Levels of TAT (A) and FX (B) in the PVT group (n = 28) were significantly higher than those in the non‐PVT group (n = 44). *p < 0.05

FIGURE 5

Relationship between NETs markers and TAT/FX. TAT complexes were positively associated with circulating levels of MPO, NE, and CitH3 in PVT patients (A–C). FX level was positively associated with circulating levels of MPO, NE, and CitH3 in PVT patients (D–F)

FIGURE 6

Patients with PVT had higher serum TF and endotoxin levels compared with non‐PVT patients. Levels of endotoxin (A) and TF (B) in the PVT group (n = 28) were significantly higher than those in the non‐PVT group (n = 44)