Figure 7.

Proposed model of the mechanisms by which neutrophils exhibit a pro-NETotic state and enhanced tendency to release NETs early after delivery in response to specific physiologic stimuli promoting thrombosis. G-CSF is a major signal inducing neutrophil release from the bone marrow, providing an important emergency mechanism by which the level of circulating neutrophils and sensitization is increased postpartum. The degree of neutrophil activation seems to be finely tuned by the unique stoichiometry of surrounding sex hormones and microdebris, which are produced by a variety of tissues and cells, including the wounded endothelium and platelets, and reach their peak concentrations shortly after term. Finally, NETs are released locally after this second hit in the vicinity of activated endothelial loci, where polymerized chains of vWF might already deploy under the presence of excessive post-delivery secondary stimuli, thus facilitating the thrombotic cascade.