Since their discovery in 2004, neutrophil extracellular traps (NETs) have been in
the center of multidisciplinary attention. While a key tool in neutrophil-mediated
immunity, these filamentous, enzyme-enriched DNA-histone complexes can be detrimental
to tissues and have been identified as an underlying factor in a range of pathological
conditions. Building on more than 20 years of research into NETs, this review places
thrombosis, the pathological formation of blood clots, in the spotlight. From this
point of view, we discuss the structure and formation of NETs, as well as the interaction
of their components with the hemostatic system, dissecting the pathways through which
NETs exert their marked effect on formation and the dissolution of thrombi. We pay
distinct attention to the latest developments in the research of a key player in NET-formation,
peptidyl-arginine-deiminase (PAD) enzymes: their types, sources, and potential cross-play
with the hemostatic machinery. Besides these molecular details, we elaborate on the
link between pathological thrombosis, NETs, and widespread conditions that represent
a debilitating public health burden worldwide, such as sepsis and neoplasms. Finally,
future implications on the treatment of thrombosis-related conditions will be discussed.
