Potential biomarker of neutrophil extracellular traps in venous thromboembolism: A systematic review

BACKGROUND Neutrophil extracellular traps (NETs) are a network of extracellular DNA produced by activated neutrophils to trap and disarm microbes. NETs increase the formation of thrombus by forming a network frame that activates platelets and initiates coagulation. NETs were involved in the thrombogenic process and have been reported in various animal models. However, the evidence of NETs’ role in venous thromboembolism (VTE) development in humans is still scarce. This review aims to discover the relationship between NETs and VTE risk. METHODS We performed literature search to identify relevant available articles from PubMed, Cochrane Library, MEDLINE, EMBASE, Clinical Key between October 2009 until October 2019. The inclusion criteria were: clinical trials published in English, involving humans as subjects, conducted within the past ten years, and had available and accessible full-text. In addition, Newcastle Ottawa Scale (NOS) was used to assess evidence quality. RESULTS Four studies with a total of 1,430 patients, i.e. three case controls and one cohort, met our eligibility criteria. All four studies' quality was good. One study of cancer patients demonstrated that NETs increase VTE risk, two other studies demonstrated NETs correlate with deep vein thrombosis (DVT), and another study demonstrated there were increasing NETs in residual vein obstruction (RVO) and increased D-dimer. All four studies found a significant association of NETs and VTE occurrence (p=0.003; p=0.018; p<0.01; p<0.001, respectively). CONCLUSIONS NETs are associated with an increased VTE risk. Further studies are necessary to determine the NETs’ role in VTE as a diagnostic biomarker or target of therapy.