Evidence of NETs in human pathological thrombosis. (A) Composite image of a human pulmonary embolism specimen obtained surgically and stained by immunohistochemistry for platelets (blue) and leukocytes (brown) showing that areas of the thrombus are rich in both cell types. Scale bar, 100 μm. Mosaic generated using MosaicJ plug-in for ImageJ.126 Immunohistochemical analysis by Alexander Savchenko. (B) Representative image of diffuse extracellular DNA staining (green) present in a surgically harvested pulmonary embolism patient specimen. Green, DNA. Scale bar, 20 μm. Anonymous specimens in A and B kindly provided by Richard Mitchell. Most recently, specimens from 11 additional patients were evaluated and biomarkers of NETs were predominantly found in the organizing stage of human venous thromboembolism.127 (C) Cell-free DNA, a plasma biomarker of NETs, is elevated in patients with thrombotic microangiopathies (left): thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), malignancies (tumor), and nonspecified cases (NOS). Patients suffering from acute TTP present significantly elevated plasma DNA compared with when in remission (right). This research was originally published in Blood. Fuchs TA et al. Circulating DNA and myeloperoxidase indicate disease activity in patients with thrombotic microangiopathies. Blood. 2012;120:1157-1164. © American Society of Hematology. Human thrombus samples were obtained by the Wagner Laboratory from Dr Richard N. Mitchell (Brigham and Women's Hospital, Boston, MA) as anonymous tissue specimens. Dr Mitchell's work was approved by Brigham and Women's Hospital Institutional Review Board 2013P000231.
