Background and aim: Over the years, various studies investigated neutrophils’ role in multiple diseases. The trace of thrombotic disorders is visible in most cases. A responsible thrombosis factor in these ailments are structures called
Neutrophil Extracellular Traps (NETs). NETs are web-like structures composed of modified chromatin filaments with histones, specific cytoplasmic, and granular proteins such as myeloperoxidase (MPO) and neutrophil elastase (NE) that snare and kill microbes. Although a part of the host defense mechanism, excessive NET formation can cause complications like thrombosis. Understanding the NET formation mechanisms and recognizing the involved factors can aid researchers in designing preventive and therapeutic strategies.Materials and method: The Pubmed database was employed in the search for Papers published on NETs in thrombotic disorders between ۲۰۰۰ and ۲۰۲۱. Among the reviewed articles, related papers were studied.Results: Findings From a total of ۴۲۶ articles, ۳۷ related ones were selected, among which existed ۱ retrospective case-control, ۴ in-vivo, ۲۲ in-vitro, and ۱۰ a combination of in-vivo and in-vitro studies. NET-mediated thrombosis is involved in various conditions such as COVID-۱۹, cancer, atherosclerosis, diabetes, thrombocytopenia, ischemic stroke, lupus, pre-eclampsia, sepsis, and hemodialysis. NETs forming in veins can cause thrombosis. Endothelial recruitment of neutrophils is done through P-selectin and von Willebrand factor (VWF); as a result, NETosis occurs. Interactions between NETs and platelets worsen this condition. NETs encourage thrombin production that leads to platelet activation. Platelets release thromboxane A۲, which increases the expression of intercellular adhesion molecule ۱ (ICAM۱) from endothelial cells. ICAM۱ improves neutrophils' interaction with endothelium, eventually leading to NETosis through the employment of reactive oxygen species (ROS), platelet-derived high mobility group protein B۱ (HMGB۱), and integrins. Another element contributing to thrombosis is NETs' recruitment of Factor XIIa, which helps the release of Weibel–Palade bodies (granules containing VWF, P-selectin, and Factor XIIa) from endothelial cells. Moreover, histones entangled in NETs bind VWF and fibrin to recruit more platelets and RBCs.Conclusion: Considering the bold presence of NETs in thrombotic disorders, investigating the factors engaged in their formation and possible therapeutic and preventive measures are of high significance.