Overall Leukocyte Levels Link Risk Factors to Von Willebrand Factor and Neutrophil Extracellular Traps in Stroke Thrombi: A Structural Equation Modeling Analysis

Lin Shi^1*Chunxiao Wei¹Guowei Ye²Panpan Zhao¹Shiqiang Ma³Yiming Qi^1,4Ruolin Zhou^1,5Yaru Zhang^1,5Yan Zhang¹Lingjie Meng¹Weihang Xu⁶Chao Li¹Shouchun Wang¹Li Sun^1*

• ¹Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Jilin University, Changchun, China., Changchun, Hebei Province, China
• ²Department of Intensive Care Unit, The First Hospital of Jilin University, Changchun, China
• ³Department of Neurosurgery Center. The First Hospital of Jilin University, Changchun, China., changchun, China
• ⁴EEG Laboratory, Neurology Department. wei fang shi ren min yi yuan, Weifang, Shandong, China., weifang, China
• ⁵Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, Shanghai Municipality, China
• ⁶School of Public Health, Jilin University, Changchun, Jilin Province, China

Background: Von Willebrand Factor (VWF) and Neutrophil Extracellular Traps (NETs) are involved in the inflammatory response during thrombi formation and are widely found in thrombi of Acute Ischemic Stroke (AIS) patients. Inflammation may mediate the relationship between cerebrovascular risk factors (such as blood glucose) and thrombi components. This study uses overall leukocyte levels to identify potential links between risk factors and VWF, NETs in thrombi. Methods: Thrombi samples and clinical data from 61 stroke patients treated at our hospital between 2017 and 2023 were collected. The Partial Least Squares Structural Equation Modeling (PLS-SEM) assessed direct and indirect associations, with leukocyte and its subtype counts as mediating variables, VWF and NETs as endogenous variables, and cerebrovascular risk factors as exogenous variables.Results: Heart dysfunction and blood glucose showed a significant negative indirect effect on VWF through the overall leukocyte levels (indirect effect = -0.119 and -0.118, P < 0.05). Overall leukocyte levels acted as a mediator between vitamin B12 and VWF levels in thrombi, displaying a positive mediatory impact (indirect effect = 0.118, P < 0.05). The decrease in VWF levels within thrombi was closely associated with an increase in discharge NIHSS scores (path coefficient = -0.353, P < 0.05).Additionally, overall leukocyte levels and homocysteine (Hcy) had significant negative effects on VWF (path coefficients = -0.384 and -0.308, P < 0.05), while vitamin B12 had a negative impact on NETs (path coefficient = -0.289, P <0.05).Conclusion: Overall leukocyte levels mediate the influence of blood glucose levels, heart dysfunction, and vitamin B12 on content VWF in thrombi in stroke patients. VWF reduction correlates with elevated discharge NIHSS scores. These cerebrovascular factors may regulate the pathological process of AIS thrombosis through inflammatory responses, guiding further exploration of the underlying mechanisms and informing clinical strategies.