Yonsei Med J.  2022 Nov;63(11):1016-1026. 10.3349/ymj.2022.0328.

Neutrophil Recruitment in Arterial Thrombus and Characteristics of Stroke Patients with Neutrophil-Rich Thrombus

• Cha MJ
• Ha J
• Lee H
• Kwon I
• Kim S
• Kim YD
• Nam HS
• Lee HS
• Song TJ
• Choi HJ
• Heo JH

• KMID: 2536372
• DOI: http://doi.org/10.3349/ymj.2022.0328

Abstract

Purpose
Neutrophils contribute to thrombosis. However, there is limited information on the temporal course of neutrophil recruitment in thrombosis, the contribution of neutrophils to thrombus growth, and the characteristics of stroke patients with neutrophil-rich thrombi.
Materials and Methods
After inducing carotid artery thrombosis in Institute of Cancer Research mice using ferric chloride, aged thrombi were produced by ligating the distal portion of the carotid artery in mice for 0.5, 1, 2, 3, 6, or 24 h. For thrombus analysis in stroke patients, we used registry data and thrombi that were obtained during intra-arterial thrombectomy. Immunohistochemistry was performed to determine thrombus composition.
Results
In the thrombi of 70 mice, Ly6G positive cell counts (neutrophils) and histone H3-positive cell counts increased in a time-dependent manner (both p<0.001). Ly6G-positive cell count was strongly correlated with histone H3-positive cell counts (r=0.910, p<0.001), but not with thrombus size (p=0.320). In 75 stroke patients, atrial fibrillation and cardioembolism were more frequent in the higher neutrophil group (32/37, 86.5%) than in the lower neutrophil group (19/38, 50%) (p=0.002). The median erythrocyte fraction was higher [52.0 (interquartile range 39.9−57.8)] in the higher neutrophil group than in the lower neutrophil group [40.3 (interquartile range 23.5−53.2)]. The fraction of neutrophils was positively correlated with that of erythrocytes (R=0.35, p=0.002).
Conclusion
Neutrophils were recruited and increased in arterial thrombosis in a time-dependent manner; however, they were not associated with the growth of formed thrombi. Neutrophil fractions in the thrombi of stroke patients appeared to be associated with atrial fibrillation and erythrocyte fraction.

Keyword

Neutrophil; thrombosis; stroke; neutrophil extracellular traps; intra-arterial thrombectomy